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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001547-46 | EudraCT Number |
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The sponsor decided to terminate study after 70% of participants had experienced a progression-free survival event.
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This multicenter study will assess the maximum tolerated dose (MTD) of capecitabine in combination with Kadcyla (trastuzumab emtansine) in participants with HER2-positive mBC or HER2-positive LA/mGC using a Phase 1 design, followed by a randomized, open-label Phase 2 part to explore the efficacy and safety of the combination of Kadcyla and capecitabine compared with Kadcyla alone in participants with mBC. The anticipated time on study treatment is until disease progression, intolerable toxicity, withdrawal of consent, or study end.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 (mBC) Cohort 1: T-DM1 + Capecitabine | Experimental | In Phase 1, Cohort 1 participants (with mBC) will receive trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at de-escalating dose levels (starting from 750 milligrams per meter squared [mg/m^2]) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, or study end. |
|
| Phase 1 (LA/mGC) Cohort 2: T-DM1 + Capecitabine | Experimental | In Phase 1, Cohort 2 participants (with LA/mGC) will receive trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (on Day 2 of first week) of every week along with capecitabine at MTD (determined in Cohort 1) via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end. |
|
| Phase 2 (mBC): T-DM1 + Capecitabine | Active Comparator | In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at MTD via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, or study end. |
|
| Phase 2 (mBC): T-DM1 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capecitabine | Drug | Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs) | A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (>) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (<) 1000 cells/millimeter cube (mm^3); Grade greater than or equal to (>/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase [DPD] deficiency only for DL 1); any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days (>7 days for DL 1); for DL -1 only: <14 full doses of capecitabine; Cycle 2 dose level <100 percent (%). | Continuously during Cycle 1 (up to 3 weeks) |
| Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks) | MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days (>7 days for DL 1); for DL -1 only: <14 full doses of capecitabine; Cycle 2 dose level <100%. | Continuously during Cycle 1 (up to 3 weeks) |
| Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to <10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. |
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Inclusion Criteria:
Metastatic Breast Cancer
Locally Advanced/Metastatic Gastric Cancer
Exclusion Criteria:
Metastatic Breast Cancer
Prior treatments before first study treatment:
Prior treatment with trastuzumab emtansine or prior enrollment in a trastuzumab emtansine-containing study, regardless of whether the patient received trastuzumab emtansine
Prior treatment with capecitabine
History of severe or unexpected reactions to fluoropyrimidine or known hypersensitivity to fluorouracil
Related capecitabine contraindications
History of intolerance or hypersensitivity to trastuzumab or murine proteins or any product component
History of exposure to high cumulative doses of anthracyclines
Brain metastases that are symptomatic or require radiation, surgery, or steroid therapy to control symptoms within 28 days before study drug
Current peripheral neuropathy of Grade >/=3
History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome
Current unstable ventricular arrhythmia requiring treatment
History of symptomatic congestive heart failure (CHF)
History of myocardial infarction or unstable angina within 6 months prior to study drug
History of left ventricular ejection fraction (LVEF) less than (<) 40% or symptomatic CHF with previous trastuzumab treatment
Severe dyspnea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy
Clinically significant malabsorption syndrome or inability to take oral medication
Current severe, uncontrolled systemic disease (such as clinically significant cardiovascular, pulmonary, or metabolic disease)
Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during study treatment
Current known active infection with human immunodeficiency virus (HIV) or hepatitis B or C
Lapatinib within 14 days before study drug
Locally Advanced/Metastatic Gastric Cancer
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fundacion Investigar | CABA | C1025ABI | Argentina | |||
| Centro Oncologico Riojano Integral (CORI) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32584367 | Derived | Cortes J, Dieras V, Lorenzen S, Montemurro F, Riera-Knorrenschild J, Thuss-Patience P, Allegrini G, De Laurentiis M, Lohrisch C, Oravcova E, Perez-Garcia JM, Ricci F, Sakaeva D, Serpanchy R, Sufliarsky J, Vidal M, Irahara N, Wohlfarth C, Aout M, Gelmon K. Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial. JAMA Oncol. 2020 Aug 1;6(8):1203-1209. doi: 10.1001/jamaoncol.2020.1796. |
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A total of 234 participants were screened, out of which, 182 participants were enrolled into the study. Out of the 182 enrolled participants, 3 participants were excluded from all safety and efficacy analyses because they did not sign correct Informed Consent Form (ICF).
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape | In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine (T-DM1) at a dose of 3.6 milligrams per kilogram (mg/kg) via intravenous (IV) infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine (Cape) at a dose level (DL) of 750 milligrams per meter squared (mg/m^2) via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, disease progression (PD), death, reasons deemed by the treating physician, or study termination by the sponsor. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 26, 2016 | May 28, 2018 |
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| Experimental |
In Phase 2, participants (with mBC) who will be randomized to this group, will receive trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, or study end. |
|
|
| Trastuzumab emtansine (T-DM1) | Drug | Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks. |
|
|
| Trastuzumab emtansine (T-DM1) | Drug | Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week. |
|
|
| Capecitabine | Drug | Capecitabine will be administered at the MTD determined in Cohort 1. |
|
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| Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 1 (LA/mGC): Percentage of Participants With DLTs | A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days; <14 full doses of capecitabine; Cycle 2 dose level <100%. | Continuously during 3 weeks |
| Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW) | MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days; <14 full doses of capecitabine; Cycle 2 dose level <100%. | Continuously during 3 weeks |
| Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall) |
| Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine | Pre-trastuzumab emtansine dose (0 hour [h]) on Day 1 Cycle 2; 15-30 minutes (min) after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
| Phase 1 (mBC): Serum Concentration of Trastuzumab | Trastuzumab was derived from trastuzumab emtansine. | Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
| Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine | Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine | AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine | Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. | Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR: >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method. | From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. | Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method. | Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1 | Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. | Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1 | TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method. | Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause | Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. | Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method. | Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1 | The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR: >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach. | Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Percentage of Participants Who Died of Any Cause | Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 2 (mBC): Overall Survival (OS) | OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients. | Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall) |
| Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. | Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall) |
| Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine | Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
| Phase 1 (LA/mGC): Serum Concentration of Trastuzumab | Trastuzumab was derived from trastuzumab emtansine. | Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
| Phase 1 (LA/mGC): Cmax of Capecitabine | Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine | AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (LA/mGC): t1/2 of Capecitabine | Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
| La Rioja |
| F5300COE |
| Argentina |
| Hospital Erasto Gaertner | Curitiba | Paraná | 81520-060 | Brazil |
| Instituto Oncologico de Ribeirao Preto - INORP | Ribeirão Preto | São Paulo | 14025-270 | Brazil |
| Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X* | São José do Rio Preto | São Paulo | 15090-000 | Brazil |
| Instituto do Cancer do Estado de Sao Paulo - ICESP | São Paulo | São Paulo | 01246-000 | Brazil |
| British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre | Vancouver | British Columbia | V5Z 4E6 | Canada |
| ICO Paul Papin; Oncologie Medicale. | Angers | 49055 | France |
| Centre Leon Berard; Departement Oncologie Medicale | Lyon | 69373 | France |
| Institut Paoli Calmettes; Oncologie Medicale | Marseille | 13273 | France |
| Institut Curie; Oncologie Medicale | Paris | 75231 | France |
| Ico Rene Gauducheau; Oncologie | Saint-Herblain | 44805 | France |
| Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo. | Berlin | 10117 | Germany |
| Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie | Bielefeld | 33604 | Germany |
| Heinrich-Heine Universitätsklinik Düsseldorf | Düsseldorf | 40225 | Germany |
| Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH | Fulda | 36043 | Germany |
| Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie | Marburg | 35043 | Germany |
| Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie) | München | 81675 | Germany |
| Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde | München | 81675 | Germany |
| Alexandras General Hospital of Athens; Oncology Department | Athens | 115 28 | Greece |
| Univ General Hosp Heraklion; Medical Oncology | Heraklion | 711 10 | Greece |
| University Hospital of Patras Medical Oncology | Pátrai | 265 04 | Greece |
| Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica | Naples | Campania | 80131 | Italy |
| Istituto Europeo Di Oncologia | Milan | Lombardy | 20141 | Italy |
| Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico | Candiolo | Piedmont | 10060 | Italy |
| Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia | Pontedera | Tuscany | 56025 | Italy |
| Hospital da Luz; Departamento de Oncologia Medica | Lisbon | 1500-650 | Portugal |
| Hospital de Santa Maria; Servico de Oncologia Medica | Lisbon | 1649-035 | Portugal |
| IPO do Porto; Servico de Oncologia Medica | Porto | 4200-072 | Portugal |
| Ivanovo Regional Oncology Dispensary | Ivanovo | 153040 | Russia |
| Blokhin Cancer Research Center; Combined Treatment | Moscow | 115478 | Russia |
| City Clinical Oncology Hospital | Moscow | 143423 | Russia |
| S-Pb clinical scientific practical center of specialized kinds of medical care (oncological) | Saint Petersburg | 197758 | Russia |
| City Oncology Dispensary | Saint Petersburg | Russia |
| Bashkirian Republican Clinical Oncology Dispensary | Ufa | 450054 | Russia |
| Institute for Oncology and Radiology of Serbia; Medical Oncology | Belgrade | 11000 | Serbia |
| Clinical Centre Nis, Clinic for Oncology | Niš | 18000 | Serbia |
| Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A | Bratislava | 833 10 | Slovakia |
| Fakultna nemocnica Trencín; Onkologicke odd. | Trenčín | 911 71 | Slovakia |
| Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | 08035 | Spain |
| FG001 | Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape | In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| FG002 | Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape | In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| FG003 | Phase 2 (mBC): T-DM1 + Cape | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| FG004 | Phase 2 (mBC): T-DM1 | In Phase 2, participants (with mBC) who were randomized in this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. |
| COMPLETED |
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| NOT COMPLETED |
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Safety population: Participants who received >/=1 dose of study drug, analyzed as per actual treatment received. In Phase 2, of 161 participants, 1 was randomized in error(received no treatment) and was excluded from safety analysis and 1 who was randomized to T-DM1 alone Arm received Capecitabine throughout study and was counted in T-DM1+Cape Arm.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape | In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| BG001 | Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape | In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| BG002 | Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape | In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| BG003 | Phase 2 (mBC): T-DM1 + Cape | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. |
| BG004 | Phase 2 (mBC): T-DM1 | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 1 (mBC): Percentage of Participants With Dose-Limiting Toxicities (DLTs) | A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting more than (>) 7 consecutive days; febrile neutropenia with absolute neutrophil count (ANC) less than (<) 1000 cells/millimeter cube (mm^3); Grade greater than or equal to (>/=) 3 diarrhea or Grade 3 hand-foot syndrome (in absence of dihydropyrimidine dehydrogenase [DPD] deficiency only for DL 1); any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days (>7 days for DL 1); for DL -1 only: <14 full doses of capecitabine; Cycle 2 dose level <100 percent (%). | Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort, which included all enrolled and treated mBC participants who did not experience any major protocol deviation and completed Cycle 1. | Posted | Number | percentage of participants | Continuously during Cycle 1 (up to 3 weeks) |
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| Primary | Phase 1 (mBC): Maximum Tolerated Dose (MTD) of Capecitabine When Combined With Trastuzumab Emtansine (3.6 mg/kg Every 3 Weeks) | MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome (in absence of DPD deficiency only for DL 1); any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days (>7 days for DL 1); for DL -1 only: <14 full doses of capecitabine; Cycle 2 dose level <100%. | Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort. | Posted | Number | mg/m^2 | Continuously during Cycle 1 (up to 3 weeks) |
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| Primary | Phase 2 (mBC): Percentage of Participants With Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Tumor response was assessed by the investigator according to RECIST v1.1. BOR was defined as percentage of participants with a complete response (CR) or partial response (PR) that was confirmed by repeat assessments >/=4 weeks after initial documentation. CR was defined as the disappearance of all target lesions (TLs) and non-TLs; short axis (SA) reduction to <10 millimeters (mm) for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. The 90% confidence Interval (CI) was computed using Clopper-Pearson approach. | Analysis was performed on Intent-to-Treat (ITT) Population, which included all participants in the randomized Phase 2 part of the study. Participants were analyzed as per the initial randomization. Participants without tumor assessment after start of study treatment were considered as non-responders. | Posted | Number | 90% Confidence Interval | percentage of participants | Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Primary | Phase 1 (LA/mGC): Percentage of Participants With DLTs | A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days; <14 full doses of capecitabine; Cycle 2 dose level <100%. | Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort, which included all enrolled and treated LA/mGC participants who did not experience any major protocol deviation and completed Cycle 1. | Posted | Number | percentage of participants | Continuously during 3 weeks |
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| Primary | Phase 1 (LA/mGC): MTD of Capecitabine When Combined With Trastuzumab Emtansine (2.4 mg/kg QW) | MTD was defined as the dose level for which the probability of DLT is equal to a protocol-specified target probability. A DLT was defined as any one of the following study treatment related toxicities: Uncomplicated Grade 4 thrombocytopenia that does not recover before Day 21; thrombocytopenia complicated with clinically significant bleeding requiring medical intervention; Grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia with ANC <1000 cells/mm^3; Grade >/=3 diarrhea or Grade 3 hand-foot syndrome; any other Grade >/=3 toxicity prohibiting start of Cycle 2; Grade 2 toxicity requiring treatment interruption for >14 days; <14 full doses of capecitabine; Cycle 2 dose level <100%. | Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort. | Posted | Number | mg/m^2 | Continuously during 3 weeks |
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| Secondary | Phase 1 (mBC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. | Analysis was performed on Phase 1 DLT-evaluable population for mBC cohort. | Posted | Number | percentage of participants | Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 3.5 years overall) |
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| Secondary | Phase 1 (mBC): Serum Concentration of Trastuzumab Emtansine | Phase 1 pharmacokinetic (PK) analysis population for mBC cohort; included all mBC participants receiving at least one dose of study medication during Phase 1 and had at least one reported serum/plasma result for PK. The PK analysis in mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | micrograms per milliliter (mcg/mL) | Pre-trastuzumab emtansine dose (0 hour [h]) on Day 1 Cycle 2; 15-30 minutes (min) after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
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| Secondary | Phase 1 (mBC): Serum Concentration of Trastuzumab | Trastuzumab was derived from trastuzumab emtansine. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | mcg/mL | Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
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| Secondary | Phase 1 (mBC): Maximum Observed Plasma Concentration (Cmax) of Capecitabine | Cmax for Capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for percent coefficient of variation (CV%) and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
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| Secondary | Phase 1 (mBC): Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) of Capecitabine | AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | hours*nanograms per milliliter (h*ng/mL) | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
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| Secondary | Phase 1 (mBC): Plasma Terminal Half-Life (t1/2) of Capecitabine | Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | hours | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
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| Secondary | Phase 1 (mBC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | ng/mL | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
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| Secondary | Phase 1 (mBC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | h*ng/mL | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
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| Secondary | Phase 1 (mBC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for mBC cohort. The PK analysis in the mBC cohort included 1 patient who was excluded from the main safety and efficacy analyses due to ICF issues. | Posted | Mean | Standard Deviation | hours | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
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| Secondary | Phase 2 (mBC): Time to Response (TTR) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. TTR was defined as the time (in months) from randomization to first documentation of confirmed PR or CR (whichever occurred first). CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. | Analysis was performed on ITT Population. Only participants with a BOR of CR or PR were included in the analysis. | Posted | Median | Full Range | months | Baseline until first documentation of confirmed PR or CR, whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Duration of Response (DoR) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. DoR was defined as the time (in months) from the date of first recorded PR/CR until the date of PD or death from any cause. CR: the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR: >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD after CR/PR were censored at the time of last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median DOR and 90% CI were estimated using Kaplan-Meier method. | Analysis was performed on ITT Population. Only participants with a BOR of CR or PR were included in the analysis. | Posted | Median | 90% Confidence Interval | months | From the documentation of response until PD, death, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. | Analysis was performed on ITT Population. | Posted | Number | percentage of participants | Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Time to Progression (TTP) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. TTP was defined as the time (in months) from randomization to the first occurrence of PD. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no documented PD at the time of study end (including participants who died before PD) or who were lost to follow-up were censored on the date of the last tumor assessment. The median TTP and 90% CI was estimated using Kaplan-Meier method. | Analysis was performed on ITT Population. | Posted | Median | 90% Confidence Interval | months | Baseline until PD, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Percentage of Participants With Treatment Failure as Assessed by the Investigator According to RECIST v1.1 | Treatment failure was defined as occurrence of any of the following event while on treatment: PD, death, withdrawal due to adverse event (AE) or laboratory abnormality, or refusal of treatment. PD as assessed by the investigator according to RECIST v1.1 was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. | Analysis was performed on ITT Population. | Posted | Number | percentage of participants | Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST v1.1 | TTF was defined as the time (in months) from randomization until treatment failure (PD, death, withdrawal due to AE or laboratory abnormality, or refusal of treatment). PD as assessed by the investigator according to RECIST v1.1 was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants who did not experience any of the above events while on study were censored on the date of their last tumor assessment. The median TTF and 90% CI was estimated using Kaplan-Meier method. | Analysis was performed on ITT Population. | Posted | Median | 90% Confidence Interval | months | Baseline until treatment failure, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Percentage of Participants With PD as Assessed by the Investigator According to RECIST v1.1 or Death From Any Cause | Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. | Analysis was performed on ITT Population. | Posted | Number | percentage of participants | Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Progression-Free Survival (PFS) as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. PFS was defined as the time (in months) from randomization until the first documented PD or death from any cause, whichever occurred first. PD was defined as >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. Participants with no PFS events were censored on the date of the last tumor assessment. Participants without post-baseline tumor assessment were censored at randomization plus 1 day. The median PFS and 90% CI was estimated using Kaplan-Meier method. | Analysis was performed on ITT Population. | Posted | Median | 90% Confidence Interval | months | Baseline until PD, death from any cause, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Percentage of Participants With Clinical Benefit as Assessed by the Investigator According to RECIST v1.1 | The clinical benefit was defined as a confirmed response of CR, PR, or stable disease (SD) that lasted for at least 6 months. Tumor response was assessed by the investigator according to RECIST v1.1. CR: the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR: >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. PD: >/=20% relative increase with >/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-TLs. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD on study. The 90% CI was computed using Clopper-Pearson approach. | Analysis was performed on ITT Population. | Posted | Number | 90% Confidence Interval | percentage of participants | Baseline until clinical benefit response, consent withdrawal, or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Percentage of Participants Who Died of Any Cause | Analysis was performed on ITT Population. | Posted | Number | percentage of participants | Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 2 (mBC): Overall Survival (OS) | OS was defined as the time (in months) from randomization until death from any cause. Participants who were alive at the time of data cut-off were censored on the date of the last follow-up assessment. Participants who were lost to follow-up were censored as having no event (alive) on the date of last contact. The median OS and 90% CI was estimated using Kaplan-Meier method, which use the patients at risk as denominator rather than the whole number of patients. | Analysis was performed on ITT Population. | Posted | Median | 90% Confidence Interval | months | Baseline until death or study end whichever occurred first (up to approximately 2.5 years overall) |
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| Secondary | Phase 1 (LA/mGC): Percentage of Participants With BOR as Assessed by the Investigator According to RECIST v1.1 | Tumor response was assessed by the investigator according to RECIST v1.1. BOR in Phase 1 was defined as percentage of participants with a CR or PR. CR was defined as the disappearance of all TLs and non-TLs; SA reduction to <10 mm for nodal TLs/non-TLs; and no new lesions. PR was defined as >/=30% decrease in SoD of TLs, taking as reference the baseline SoD; no progression in non-TLs; and no new lesions. | Analysis was performed on Phase 1 DLT-evaluable population for LA/mGC cohort. | Posted | Number | percentage of participants | Baseline until CR/PR, consent withdrawal, or study end whichever occurred first (up to approximately 1.5 years overall) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): Serum Concentration of Trastuzumab Emtansine | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | mcg/mL | Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): Serum Concentration of Trastuzumab | Trastuzumab was derived from trastuzumab emtansine. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | mcg/mL | Pre-trastuzumab emtansine dose (0 h) on Day 1 Cycle 2; 15-30 min after end of trastuzumab emtansine infusion (maximum infusion duration = 90 min) on Day 2 Cycle 1 and Day 1 Cycle 2 (cycle length=21 days) |
|
| |||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): Cmax of Capecitabine | Cmax for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | ng/mL | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
|
| |||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): AUC(0-inf) of Capecitabine | AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | h*ng/mL | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
|
| |||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): t1/2 of Capecitabine | Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for capecitabine was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | hours | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
|
| |||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): Cmax of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Cmax for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | ng/mL | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
|
| |||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): AUC(0-inf) of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. AUC(0-inf) is the measure of total drug exposure and is dependent on the total amount of drug absorbed. AUC(0-inf) for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | h*ng/mL | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
|
| |||||||||||||||||||||||||||||
| Secondary | Phase 1 (LA/mGC): t1/2 of 5-Fluorouracil (Metabolite of Capecitabine) | 5-fluorouracil is a metabolite of capecitabine. Plasma terminal half-life is the time measured for the plasma drug concentration to decrease by one half during the elimination phase of the drug. t1/2 for 5-fluorouracil was estimated from plasma concentration versus time data using non-compartmental methods of analysis. Reported dispersion values are for CV% and not for standard deviation. | Analysis was performed on Phase 1 PK analysis population for LA/mGC cohort. | Posted | Mean | Standard Deviation | hours | Pre-capecitabine dose (0 h) and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h post-capecitabine dose on Day 1 Cycle 1 |
|
|
Phase 1: Baseline up to 42 days after last dose (up to approximately 1.5 years overall); Phase 2: Baseline up to 42 days after last dose (up to approximately 2.5 years overall)
Safety population included all participants who received >/=1 dose of study drug. Participants were analyzed as per actual treatment received. In Phase 2, out of 161 participants, 1 participant was randomized in error (did not receive any treatment) and was excluded from safety analysis and 1 participant who was randomized to T-DM1 alone Arm received Capecitabine throughout study and was counted in T-DM1+Cape Arm.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1 (mBC) Cohort 1 (DL 1): T-DM1 + Cape | In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 750 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. | 4 | 7 | 0 | 7 | 7 | 7 |
| EG001 | Phase 1 (mBC) Cohort 1 (DL -1): T-DM1 + Cape | In Phase 1, Cohort 1 participants (with mBC) received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion (on Day 1 [on Day 2 for Cycle 1] of each 21-day cycle) along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. | 3 | 5 | 2 | 5 | 5 | 5 |
| EG002 | Phase 1 (LA/mGC) Cohort 2 (DL -1): T-DM1 + Cape | In Phase 1, Cohort 2 participants (with LA/mGC) received trastuzumab emtansine at a dose of 2.4 mg/kg via IV infusion on Day 1 (Day 2 of first week) of every week along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 followed by a 7-day rest period, in each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. | 3 | 6 | 4 | 6 | 6 | 6 |
| EG003 | Phase 2 (mBC): T-DM1 + Cape | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle along with capecitabine at a dose level of 700 mg/m^2 via tablet orally twice daily on Days 1-14 of each 21-day cycle until unacceptable toxicity, withdrawal of consent, PD, death, reasons deemed by the treating physician, or study termination by the sponsor. | 18 | 82 | 11 | 82 | 75 | 82 |
| EG004 | Phase 2 (mBC): T-DM1 | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. | 21 | 78 | 10 | 78 | 64 | 78 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cerebral cyst | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Radiation necrosis | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Device related sepsis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v20.0 | Non-systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tumour excision | Surgical and medical procedures | MedDRA v20.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Intestinal haematoma | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Mesenteric vein thrombosis | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Wound sepsis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Anuria | Renal and urinary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hepatocellular injury | Hepatobiliary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Fracture displacement | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Uterine polyp | Reproductive system and breast disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Anal haemorrhage | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Chapped lips | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Limb mass | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Weight bearing difficulty | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Catheter site rash | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Mucosal dryness | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Aphonia | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Vocal cord paralysis | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Nasal ulcer | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Macule | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Eye infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hepatocellular injury | Hepatobiliary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cell death | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Eye haemorrhage | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blepharospasm | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blindness | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pterygium | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Retinal ischaemia | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Procedural headache | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Arthropod sting | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Eye contusion | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin injury | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Affect lability | Psychiatric disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Deafness unilateral | Ear and labyrinth disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Middle ear effusion | Ear and labyrinth disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Bloody discharge | Vascular disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gilbert's syndrome | Congenital, familial and genetic disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Cushingoid | Endocrine disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Breast mass | Reproductive system and breast disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin lesion excision | Surgical and medical procedures | MedDRA v20.0 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Nasal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Sinus disorder | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Spider naevus | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Telangiectasia | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Pleural infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Restless legs syndrome | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Periorbital haematoma | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tooth extraction | Surgical and medical procedures | MedDRA v20.0 | Non-systematic Assessment |
| |
| Tumour excision | Surgical and medical procedures | MedDRA v20.0 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Liver palpable | Investigations | MedDRA v20.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
The sponsor decided to terminate the study after 70% of participants had experienced a PFS event. Participants were allowed to continue treatment by enrolling into study NCT00781612 or by moving to commercial drug, depending on their country.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 7, 2017 | May 28, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D013274 | Stomach Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069287 | Capecitabine |
| D000080044 | Ado-Trastuzumab Emtansine |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D008453 | Maytansine |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D000068878 | Trastuzumab |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Race: N/A (as per local regulation) |
|
| Race: Black |
|
| Race: Asian |
|
| Race: Mixed |
|
| Ethnicity: Hispanic/Latino |
|
| Ethnicity: Chinese |
|
| Ethnicity: Other |
|
| Ethnicity: N/A (as per local regulation) |
|
| Ethnicity: Unknown |
|
| Ethnicity: Mixed |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 | Phase 2 (mBC): T-DM1 | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. |
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| Counts |
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| Participants |
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| Units |
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| Counts |
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| Participants |
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| OG001 | Phase 2 (mBC): T-DM1 | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. |
|
|
|
|
In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.
|
|
|
|
In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor.
|
|
|
|
In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. |
|
|
| OG001 | Phase 2 (mBC): T-DM1 | In Phase 2, participants (with mBC) who were randomized to this group received trastuzumab emtansine at a dose of 3.6 mg/kg via IV infusion on Day 1 of each 21-day cycle until investigator-assessed PD, unacceptable toxicity, withdrawal of consent, death, reasons deemed by the treating physician, or study termination by the Sponsor. |
|
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