A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzu... | NCT00951665 | Trialant
NCT00951665
Sponsor
Genentech, Inc.
Status
Completed
Last Update Posted
Jun 24, 2016Estimated
Enrollment
107Actual
Phase
Phase 1Phase 2
Conditions
Metastatic Breast Cancer
Interventions
paclitaxel
pertuzumab [Perjeta]
trastuzumab emtansine [Kadcyla]
paclitaxel
trastuzumab emtansine [Kadcyla]
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT00951665
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
TDM4652g
Secondary IDs
ID
Type
Description
Link
GO01355
Other Identifier
Hoffmann-La Roche
Brief Title
A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer
Official Title
A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer
Acronym
Not provided
Organization
Genentech, Inc.INDUSTRY
Status Module
Record Verification Date
May 2016
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Aug 2009
Primary Completion Date
Feb 2012Actual
Completion Date
Jun 2013Actual
First Submitted Date
Aug 3, 2009
First Submission Date that Met QC Criteria
Aug 3, 2009
First Posted Date
Aug 4, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 4, 2016
Results First Submitted that Met QC Criteria
May 17, 2016
Results First Posted Date
Jun 24, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 17, 2016
Last Update Posted Date
Jun 24, 2016Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Genentech, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This Phase Ib-IIa, multi-institutional, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics and feasibility of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion in combination with paclitaxel (and pertuzumab, if applicable) in patients with human epidermal growth factor receptor 2-positive (HER2-positive), locally advanced or metastatic breast cancer.
Detailed Description
Not provided
Conditions Module
Conditions
Metastatic Breast Cancer
Keywords
Trastuzumab DM1 (T-DM1)
Trastuzumab emtansine
Armed Herceptin
HER2
HER2+
HER2 Positive Breast Cancer
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
107Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Phase lb Regimen 1
Experimental
Participants received trastuzumab emtansine (T-DM1) every three weeks (Q3W) + paclitaxel weekly (QW) intravenously.
Participants received maximum tolerated dose (MTD) from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m^2 QW intravenously.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
paclitaxel
Drug
Intravenous repeating dose
Phase IIa Group A
Phase IIa Group B
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later
Number of Participants With Dose Limiting Toxicity (DLT) of the Combination of T-DM1 and Paclitaxel When T-DM1 Was Administered on Either an Q3W or QW Schedule for Both With and Without Pertuzumab Treatment
DLT is defined as one of the following toxicities related to study drug during Cycle 1, according to the NCI CTCAE, Version 3: Grade 3 or higher non-hematologic AEs; Grade 3 or higher elevation of serum bilirubin, hepatic transaminases, or alkaline phosphatase; Grade 4 or higher thrombocytopenia; Grade 4 or higher neutropenia; any subjectively intolerable toxicity related to T-DM1, paclitaxel, or pertuzumab; any treatment-related toxicity prohibiting the start of the second cycle of treatment and/or prompting to a dose delay or modification during the DLT observation period, such as prompting a dose reduction at Cycle 2 Day1.
Up to 23 days
Maximum Tolerated Dose of T-DM1 When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab
The MTD was defined as the highest dose of T-DM1 and paclitaxel at which 0 of 3 participants or 1 of 6 experienced a DLT, when T-DM1 (Q3W or QW) and paclitaxel (QW) was administered with and without pertuzumab treatment.
Days 1 to 21
Maximum Tolerated Dose of Paclitaxel When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Participants With Objective Response Rate (ORR)
Participants with measurable disease (at least one lesion 2 centimeters [cm] or more on computed tomography (CT) scan or 1 cm or more on spiral CT scan) were considered for OR. ORR is defined as the percentage of patients with a complete response (CR)/partial response (PR) determined on two consecutive tumor assessments at least 4 weeks apart based on modified Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). CR defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR defined as at least 30 percent decrease in sum of the longest diameters of the target lesions taking as reference the baseline sum longest diameters.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Histologically documented HER2-positive locally advanced or metastatic breast cancer
Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments
Prior trastuzumab in any line of therapy (Phase Ib patients only)
No prior T-DM1 or pertuzumab therapy
Measurable or evaluable disease
Cardiac ejection fraction >=50% by either echocardiogram or multigated acquisition scan
Life expectancy >= 90 days as assessed by the investigator
Exclusion Criteria:
Fewer than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal or radiotherapy for the treatment of breast cancer, with the following exceptions: hormone-replacement therapy or oral contraceptives are allowed; palliative radiation therapy involving <=25% of marrow-bearing bone is allowed if completed within >= 14 days prior to first study treatment
History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued
Peripheral neuropathy of Grade >= 2 per NCI CTCAE, Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy (Phase Ib patients)
Peripheral neuropathy of Grade >/=1 per NCI CTCAE, Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy (Phase IIa patients)
History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 500 mg/m^2; Liposomal doxorubicin > 900 mg/m^2; Epirubicin > 720 mg/m^2
History of clinically significant cardiac dysfunction
Brain metastases that are untreated, or progressive, or have required any type of therapy (including radiation, surgery, or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment.
History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, basal cell carcinoma, or synchronous or subsequent HER2-positive breast cancer or other malignancy with a similar expected curative outcome
Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res. 2016 Mar 15;18(1):34. doi: 10.1186/s13058-016-0691-7.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
This study was conducted from 21 Jul 2009 to 04 Jun 2013 at 5 centers (4 centers for Phase Ib and 5 centers for Phase IIa) in the United States.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase Ib Regimen 1
Participants received trastuzumab emtansine (T-DM1) every three weeks (Q3W) + paclitaxel weekly (QW) intravenously.
Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m^2 QW + pertuzumab Q3W intravenously.
Drug: paclitaxel
Drug: pertuzumab [Perjeta]
Drug: trastuzumab emtansine [Kadcyla]
pertuzumab [Perjeta]
Drug
Intravenous repeating dose
Phase IIa Group B
Phase Ib Regimen 2
Phase Ib Regimen 4
trastuzumab emtansine [Kadcyla]
Drug
Intravenous escalating dose
Phase Ib Regimen 2
Phase Ib Regimen 3
Phase Ib Regimen 4
Phase lb Regimen 1
paclitaxel
Drug
Intravenous escalating dose
Phase Ib Regimen 2
Phase Ib Regimen 3
Phase Ib Regimen 4
Phase lb Regimen 1
trastuzumab emtansine [Kadcyla]
Drug
Intravenous repeating dose
Phase IIa Group A
Phase IIa Group B
The MTD was defined as the highest dose of paclitaxel at which 0 of 3 participants or 1 of 6 experienced a DLT, when paclitaxel (QW) and T-DM1 (Q3W or QW) was administered with and without pertuzumab treatment.
Days 1 to 21
Number of Participants in Phase IIa of the Study Who Received 12 or More Paclitaxel Doses in Combination With T-DM1 and/or Pertuzumab
Participants in Phase IIa received T-DM1 Q3W and paclitaxel in Group A and T-DM1, paclitaxel, and pertuzumab in Group B.
From Day 1 to 15 weeks
Number of Participants Who Had Adverse Events That Required Dose Modification of T-DM1 or Paclitaxel
Participants were assessed for toxicity prior to each dose of T-DM1 and paclitaxel; dosing occurred only if the clinical assessment and laboratory test values were acceptable. Dose modifications included dose delayed or any dose reduction. Participants in whom significant toxicities had not recovered to the treatment range defined by the dose modification guidelines at the time of their next scheduled dose, had their dose of T-DM1 and/or paclitaxel delayed or reduced for up to 21 days.
Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later
Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen
Cmax of serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion)
Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After Q3W Dose Regimen
Cmax of plasma DM1 in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion)
Area Under the Serum Concentration-time Curve of Total Exposure (AUC0-Day 21) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen
AUC0-21 for serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.
Pre- and post-dose (0.25 and 4 hours and Day 8 [before paclitaxel infusion) for Cycle 1 and pre- and post-dose (0.25 and 4 hours) for Cycle 2 (each cycle of 21 days)
Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen
Cmax for serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis when T-DM1 was administered QW.
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion)
Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After QW Dose Regimen
Cmax for plasma DM1 in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered QW
Pre-dose, and 0.25 and 4 hours post-dose on Day 1, and Day 8 (before T-DM1 dose)
Area Under the Serum Concentration-time Curve of Total Exposure (AUClast) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen
AUClast for serum T-DM1 and serum total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered QW
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before T-DM1 dose)
Maximum Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence T-DM1) and Cycle 2 (in the Presence T-DM1)
Plasma Cmax of paclitaxel (65 mg/m^2 and 80 mg/m^2) for Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1) was estimated by non-compartmental analysis.
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
Area Under Plasma Concentration - Time Curve of Paclitaxel From Time 0 to Infinity (AUC0-inf) in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Plasma AUC0-inf of paclitaxel (65 mg/m^2 and 80 mg/m^2) was estimated by non-compartmental analysis in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
An Elimination Half-life (t1/2) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Plasma t1/2 of paclitaxel (65 mg/m^2 and 80 mg/m^2) was estimated by non-compartmental analysis in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
Plasma Clearance (CL) of Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Plasma CL of paclitaxel (65 mg/m^2 and 80 mg/m^2) was estimated by non-compartmental analysis for in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
An Apparent Volume of Distribution at Steady-state (Vss) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state which is estimated by (D/AUC[0-inf]) X (AUMC[0-inf])/AUC[0-inf]) where D is the dose of study drug, AUMC(0-inf) is the area under the first moment curve extrapolated to infinity and AUC(0-inf) is the area under the plasma concentration-time curve from time zero to infinite time. The Vss of paclitaxel (65 mg/m2 and 80 mg/m2) is observed in Cycle 1 (in the absence of T-DM1) and Cycle 2 (in the presence of T-DM1).
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
Number of Participants With Change From Baseline in Cardiac Function
Change in cardiac functions i.e., left ventricular ejection fraction (LVEF) and segmental wall abnormalities were assessed by echocardiogram or multigated acquisition scans. LVEF was assessed as change from baseline as 0 to <15%, >=15 to <25%, >=25%, and missing values.
Baseline (30 days prior to study dose), end of Cycle 2, and then every three cycles in Phase Ib and every four cycles in Phase IIa throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
Duration of Objective Response
Duration of OR is only calculated for participants with OR and is defined as the time from the first tumor assessment that supports the participant's OR to disease progression or death.
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
Percentage of Participants With Clinical Benefit
Clinical benefit is defined as CR, PR, or stable disease (SD) of 6 months or more duration as assessed by the investigator. CR and PR are identified in previous outcome measure. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started. PD is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
Progression-free Survival (PFS)
PFS is defined as the time from the first day of study treatment to documented disease progression or death on study i.e., death due to any cause within 30-days of last dose of study treatment, whichever occurs first.
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
Aurora
Colorado
80045
United States
Boston
Massachusetts
02115
United States
Detroit
Michigan
48201
United States
New York
New York
10065
United States
FG002
Phase Ib Regimen 3
Participants received T-DM1 QW + paclitaxel QW intravenously.
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Safety Population: All participants who received at least a single dose of study medication were included.
Posted
Number
participants
Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m^2 QW intravenously.
OG005
Phase IIa Group B
Participants received MTD from Phase 1b , i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m^2 QW, plus pertuzumab Q3W intravenously.
Units
Counts
Participants
OG00026
OG00110
OG00221
OG003
Title
Denominators
Categories
Any AEs
Title
Measurements
OG00026
OG00110
OG00221
OG003
Primary
Number of Participants With Dose Limiting Toxicity (DLT) of the Combination of T-DM1 and Paclitaxel When T-DM1 Was Administered on Either an Q3W or QW Schedule for Both With and Without Pertuzumab Treatment
DLT is defined as one of the following toxicities related to study drug during Cycle 1, according to the NCI CTCAE, Version 3: Grade 3 or higher non-hematologic AEs; Grade 3 or higher elevation of serum bilirubin, hepatic transaminases, or alkaline phosphatase; Grade 4 or higher thrombocytopenia; Grade 4 or higher neutropenia; any subjectively intolerable toxicity related to T-DM1, paclitaxel, or pertuzumab; any treatment-related toxicity prohibiting the start of the second cycle of treatment and/or prompting to a dose delay or modification during the DLT observation period, such as prompting a dose reduction at Cycle 2 Day1.
Safety Population: All participants of the dose finding part of the study (phase 1b) who received at least a single dose of study medication were included. Participants in Phase 1b (Regimen 1, Regimen 2, Regimen 3 and Regimen 4 [60 participants]) were considered for this analysis.
Posted
Number
participants
Up to 23 days
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Maximum Tolerated Dose of T-DM1 When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab
The MTD was defined as the highest dose of T-DM1 and paclitaxel at which 0 of 3 participants or 1 of 6 experienced a DLT, when T-DM1 (Q3W or QW) and paclitaxel (QW) was administered with and without pertuzumab treatment.
Safety Population: All participants of the dose finding part of the study (phase 1b) who received at least a single dose of study medication were included.
Posted
Number
mg/kg
Days 1 to 21
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Maximum Tolerated Dose of Paclitaxel When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab
The MTD was defined as the highest dose of paclitaxel at which 0 of 3 participants or 1 of 6 experienced a DLT, when paclitaxel (QW) and T-DM1 (Q3W or QW) was administered with and without pertuzumab treatment.
Safety Population: All participants of the dose finding part of the study (phase 1b) who received at least a single dose of study medication were included.
Posted
Number
mg/m^2
Days 1 to 21
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Number of Participants in Phase IIa of the Study Who Received 12 or More Paclitaxel Doses in Combination With T-DM1 and/or Pertuzumab
Participants in Phase IIa received T-DM1 Q3W and paclitaxel in Group A and T-DM1, paclitaxel, and pertuzumab in Group B.
Safety Population: All participants of the phase IIa part of the study who received at least a single dose of study medication and did not have disease progression in the first 12 weeks of study treatment were included.
Posted
Number
participants
From Day 1 to 15 weeks
ID
Title
Description
OG000
Phase IIa Group A
Participants received MTD from Phase Ib i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m^2 QW intravenously.
OG001
Phase IIa Group B
Participants received T-DM1 3.6mg/kg Q3W, paclitaxel 80mg/m^2 QW, and pertuzumab 420 mg Q3W intravenously.
Units
Counts
Participants
OG000
Primary
Number of Participants Who Had Adverse Events That Required Dose Modification of T-DM1 or Paclitaxel
Participants were assessed for toxicity prior to each dose of T-DM1 and paclitaxel; dosing occurred only if the clinical assessment and laboratory test values were acceptable. Dose modifications included dose delayed or any dose reduction. Participants in whom significant toxicities had not recovered to the treatment range defined by the dose modification guidelines at the time of their next scheduled dose, had their dose of T-DM1 and/or paclitaxel delayed or reduced for up to 21 days.
Safety Population: All participants who received at least a single dose of study medication were included.
Posted
Number
participants
Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Participants received T-DM1 QW + paclitaxel QW intravenously.
Primary
Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen
Cmax of serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.
Pharmacokinetics (PK) population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.
Posted
Mean
Standard Deviation
microgram per millilitre (Mcg /mL)
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion)
ID
Title
Description
OG000
Phase Ib Cohort A
Participants received 2 mg/kg T-DM1 Q3W and 65 mg/m^2 paclitaxel QW intravenously.
OG001
Phase Ib Cohort B
Participants received 2 mg/kg T-DM1 Q3W and 80 mg/m^2 paclitaxel QW intravenously.
OG002
Phase Ib Cohort 1
Participants received 2.4 mg/kg T-DM1 Q3W and 65 mg/m^2 paclitaxel QW intravenously.
OG003
Primary
Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After Q3W Dose Regimen
Cmax of plasma DM1 in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.
Posted
Mean
Full Range
nano gram per milliliter (ng/mL)
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion)
ID
Title
Description
OG000
Phase Ib Cohort B
Participants received 2 mg/kg T-DM1 Q3W and 80 mg/m^2 paclitaxel QW intravenously.
OG001
Phase Ib Cohort 1
Participants received 2.4 mg/kg T-DM1 Q3W and 65 mg/m^2 paclitaxel QW intravenously.
OG002
Phase Ib Cohort J
Participants received 2.4 mg/kg T-DM1 Q3W and 80 mg/m^2 paclitaxel QW intravenously.
OG003
Phase Ib Cohort D
Primary
Area Under the Serum Concentration-time Curve of Total Exposure (AUC0-Day 21) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen
AUC0-21 for serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.
Posted
Mean
Standard Deviation
day*mcg/mL
Pre- and post-dose (0.25 and 4 hours and Day 8 [before paclitaxel infusion) for Cycle 1 and pre- and post-dose (0.25 and 4 hours) for Cycle 2 (each cycle of 21 days)
ID
Title
Description
OG000
Phase Ib Cohort A
Participants received 2 mg/kg T-DM1 Q3W and 65 mg/m^2 paclitaxel QW intravenously.
OG001
Phase Ib Cohort B
Participants received 2 mg/kg T-DM1 Q3W and 80 mg/m^2 paclitaxel QW intravenously.
OG002
Phase Ib Cohort 1
Participants received 2.4 mg/kg T-DM1 Q3W and 65 mg/m^2 paclitaxel QW intravenously.
Primary
Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen
Cmax for serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis when T-DM1 was administered QW.
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.
Posted
Mean
Standard Deviation
mcg/mL
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion)
ID
Title
Description
OG000
Phase Ib Cohort 6
Participants received 1.2 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG001
Phase Ib Cohort 7
Participants received 1.6 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG002
Phase Ib Cohort 8
Participants received 2.0 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG003
Phase Ib Cohort F
Primary
Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After QW Dose Regimen
Cmax for plasma DM1 in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered QW
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.
Posted
Mean
Full Range
ng/mL
Pre-dose, and 0.25 and 4 hours post-dose on Day 1, and Day 8 (before T-DM1 dose)
ID
Title
Description
OG000
Phase Ib Cohort 6
Participants received 1.2 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG001
Phase Ib Cohort 7
Participants received 1.6 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG002
Phase Ib Cohort 8
Participants received 2.0 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG003
Phase Ib Cohort F
Participants received 2.4 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
Primary
Area Under the Serum Concentration-time Curve of Total Exposure (AUClast) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen
AUClast for serum T-DM1 and serum total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered QW
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.
Posted
Mean
Standard Deviation
day*µg/mL
Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before T-DM1 dose)
ID
Title
Description
OG000
Phase Ib Cohort 6
Participants received 1.2 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG001
Phase Ib Cohort 7
Participants received 1.6 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG002
Phase Ib Cohort 8
Participants received 2.0 mg/kg T-DM1 QW and 65 mg/m^2 paclitaxel QW intravenously.
OG003
Primary
Maximum Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence T-DM1) and Cycle 2 (in the Presence T-DM1)
Plasma Cmax of paclitaxel (65 mg/m^2 and 80 mg/m^2) for Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1) was estimated by non-compartmental analysis.
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. "n" denotes number of participants who received the indicated study drug.
Posted
Mean
Standard Deviation
ng/mL
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
ID
Title
Description
OG000
Phase Ib
For paclitaxel, plasma concentration-time data were available from 47 patients receiving administration of paclitaxel at QW doses of 65 and 80 mg/m^2.
Units
Counts
Participants
OG000
Primary
Area Under Plasma Concentration - Time Curve of Paclitaxel From Time 0 to Infinity (AUC0-inf) in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Plasma AUC0-inf of paclitaxel (65 mg/m^2 and 80 mg/m^2) was estimated by non-compartmental analysis in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. "n" denotes number of participants who received the indicated study drug.
Posted
Mean
Standard Deviation
hr*ng/mL
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
ID
Title
Description
OG000
Phase Ib
For paclitaxel, plasma concentration-time data were available from 47 patients receiving administration of paclitaxel at QW doses of 65 and 80 mg/m^2.
Units
Counts
Participants
OG000
Primary
An Elimination Half-life (t1/2) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Plasma t1/2 of paclitaxel (65 mg/m^2 and 80 mg/m^2) was estimated by non-compartmental analysis in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. "n" denotes number of participants who received the indicated study drug.
Posted
Mean
Standard Deviation
hr
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
ID
Title
Description
OG000
Phase Ib
For paclitaxel, plasma concentration-time data were available from 47 patients receiving administration of paclitaxel at QW doses of 65 and 80 mg/m^2.
Units
Counts
Participants
OG000
Primary
Plasma Clearance (CL) of Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Plasma CL of paclitaxel (65 mg/m^2 and 80 mg/m^2) was estimated by non-compartmental analysis for in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. "n" denotes number of participants who received the indicated study drug.
Posted
Mean
Standard Deviation
L/hr/m^2
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
ID
Title
Description
OG000
Phase Ib
For paclitaxel, plasma concentration-time data were available from 47 patients receiving administration of paclitaxel at QW doses of 65 and 80 mg/m^2.
Units
Counts
Participants
OG000
Primary
An Apparent Volume of Distribution at Steady-state (Vss) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state which is estimated by (D/AUC[0-inf]) X (AUMC[0-inf])/AUC[0-inf]) where D is the dose of study drug, AUMC(0-inf) is the area under the first moment curve extrapolated to infinity and AUC(0-inf) is the area under the plasma concentration-time curve from time zero to infinite time. The Vss of paclitaxel (65 mg/m2 and 80 mg/m2) is observed in Cycle 1 (in the absence of T-DM1) and Cycle 2 (in the presence of T-DM1).
PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. "n" denotes number of participants who received the indicated study drug.
Posted
Mean
Standard Deviation
L/m^2
Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2
ID
Title
Description
OG000
Phase Ib
For paclitaxel, plasma concentration-time data were available from 47 patients receiving administration of paclitaxel at QW doses of 65 and 80 mg/m^2.
Units
Counts
Primary
Number of Participants With Change From Baseline in Cardiac Function
Change in cardiac functions i.e., left ventricular ejection fraction (LVEF) and segmental wall abnormalities were assessed by echocardiogram or multigated acquisition scans. LVEF was assessed as change from baseline as 0 to <15%, >=15 to <25%, >=25%, and missing values.
Safety Population: All participants who received at least a single dose of study medication were included.
Posted
Number
participants
Baseline (30 days prior to study dose), end of Cycle 2, and then every three cycles in Phase Ib and every four cycles in Phase IIa throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Participants received T-DM1 QW + paclitaxel QW intravenously.
OG003
Secondary
Percentage of Participants With Objective Response Rate (ORR)
Participants with measurable disease (at least one lesion 2 centimeters [cm] or more on computed tomography (CT) scan or 1 cm or more on spiral CT scan) were considered for OR. ORR is defined as the percentage of patients with a complete response (CR)/partial response (PR) determined on two consecutive tumor assessments at least 4 weeks apart based on modified Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). CR defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR defined as at least 30 percent decrease in sum of the longest diameters of the target lesions taking as reference the baseline sum longest diameters.
An efficacy population: All participants who received at least a single dose of study medication were included. Participants with measurable disease were considered for OR.
Posted
Number
percentage of participants
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Duration of OR is only calculated for participants with OR and is defined as the time from the first tumor assessment that supports the participant's OR to disease progression or death.
An efficacy population: All participants who received at least a single dose of study medication were included. Participants with OR were considered for this outcome measure.
Posted
Median
95% Confidence Interval
months
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Participants received T-DM1 QW + paclitaxel QW intravenously.
OG003
Phase Ib Regimen 4
Secondary
Percentage of Participants With Clinical Benefit
Clinical benefit is defined as CR, PR, or stable disease (SD) of 6 months or more duration as assessed by the investigator. CR and PR are identified in previous outcome measure. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started. PD is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
An efficacy population: All participants who received at least a single dose of study medication were included.
Posted
Number
percentage of participants
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
PFS is defined as the time from the first day of study treatment to documented disease progression or death on study i.e., death due to any cause within 30-days of last dose of study treatment, whichever occurs first.
An efficacy population: All participants who received at least a single dose of study medication were included.
Posted
Median
Full Range
months
Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first
ID
Title
Description
OG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Participants received T-DM1 QW + paclitaxel QW intravenously.
OG003
Phase Ib Regimen 4
Time Frame
Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later (Approximately 4 years)
Description
SAEs and other AEs were collected in the safety population, which was defined as all participants who received at least a single dose of study medication. There was one SAE that lead to death and the preferred term was not captured for it. The same SAE was captured as 'Death - unknown cause' in the below SAE table.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Phase Ib Regimen 1
Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m^2 QW intravenously.
6
22
22
22
EG005
Phase IIa Group B
Participants received MTD from Phase 1b , i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m^2 QW, plus pertuzumab Q3W intravenously.
6
22
22
22
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG0030 affected3 at risk
EG004
Neutropenia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Extrasystoles
Cardiac disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Death - unknown cause
General disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Thrombosis in device
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Ulcer
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Fatigue
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Chills
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Device occlusion
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0002 affected26 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0012 affected10 at risk
EG0022 affected21 at risk
EG003
Sepsis
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Device related infection
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Campylobacter infection
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Influenza
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Streptococcal sepsis
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Subdural Haematoma
Injury, poisoning and procedural complications
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Haemoglobin Decreased
Investigations
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Groin pain
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Pathological fracture
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Akathisia
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Mental Status Changes
Psychiatric disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Haemorrhage
Vascular disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected26 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Fatigue
General disorders
MedDRA (16.0)
Systematic Assessment
EG00023 affected60 at risk
EG0018 affected10 at risk
EG00218 affected21 at risk
EG0032 affected3 at risk
EG00416 affected22 at risk
EG00519 affected22 at risk
Mucosal Inflammation
General disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0013 affected10 at risk
EG0023 affected21 at risk
EG003
Oedema Peripheral
General disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0012 affected10 at risk
EG0023 affected21 at risk
EG003
Pyrexia
General disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0027 affected21 at risk
EG003
Chills
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Chest pain
General disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Gait disturbance
General disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG00010 affected60 at risk
EG0016 affected10 at risk
EG0028 affected21 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0005 affected60 at risk
EG0017 affected10 at risk
EG0026 affected21 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Nail disorder
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Onycholysis
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0022 affected21 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Photosensitivity reaction
Skin and subcutaneous tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0008 affected60 at risk
EG0012 affected10 at risk
EG0024 affected21 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0006 affected60 at risk
EG0011 affected10 at risk
EG0026 affected21 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0012 affected10 at risk
EG0022 affected21 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (16.0)
Systematic Assessment
EG0009 affected60 at risk
EG0016 affected10 at risk
EG0029 affected21 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0008 affected60 at risk
EG0012 affected10 at risk
EG0024 affected21 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0003 affected60 at risk
EG0011 affected10 at risk
EG0023 affected21 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0012 affected10 at risk
EG0022 affected21 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0003 affected60 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Eye infection
Infections and infestations
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0008 affected60 at risk
EG0013 affected10 at risk
EG0027 affected21 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0007 affected60 at risk
EG0011 affected10 at risk
EG0022 affected21 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0011 affected10 at risk
EG0023 affected21 at risk
EG003
Joint stiffness
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (16.0)
Systematic Assessment
EG0007 affected60 at risk
EG0011 affected10 at risk
EG0028 affected21 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (16.0)
Systematic Assessment
EG0005 affected60 at risk
EG0013 affected10 at risk
EG0027 affected21 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Depression
Psychiatric disorders
MedDRA (16.0)
Systematic Assessment
EG0007 affected60 at risk
EG0010 affected10 at risk
EG0020 affected21 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0012 affected10 at risk
EG0022 affected21 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0012 affected10 at risk
EG0021 affected21 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0012 affected10 at risk
EG0024 affected21 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0022 affected21 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Weight increased
Investigations
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Weight decreased
Investigations
MedDRA (16.0)
Systematic Assessment
EG0000 affected60 at risk
EG0011 affected10 at risk
EG0022 affected21 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0021 affected21 at risk
EG003
Hypertension
Vascular disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0010 affected10 at risk
EG0023 affected21 at risk
EG003
Hot flush
Vascular disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Lymphoedema
Vascular disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected60 at risk
EG0010 affected10 at risk
EG0023 affected21 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA (16.0)
Systematic Assessment
EG0000 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0006 affected60 at risk
EG0012 affected10 at risk
EG0025 affected21 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0003 affected60 at risk
EG0013 affected10 at risk
EG0027 affected21 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0012 affected10 at risk
EG0024 affected21 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (16.0)
Systematic Assessment
EG0003 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Dry eye
Eye disorders
MedDRA (16.0)
Systematic Assessment
EG0008 affected60 at risk
EG0013 affected10 at risk
EG0029 affected21 at risk
EG003
Vision blurred
Eye disorders
MedDRA (16.0)
Systematic Assessment
EG0005 affected60 at risk
EG0013 affected10 at risk
EG0026 affected21 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA (16.0)
Systematic Assessment
EG0006 affected60 at risk
EG0012 affected10 at risk
EG0021 affected21 at risk
EG003
Conjunctivitis
Eye disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Photophobia
Eye disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Visual impairment
Eye disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0021 affected21 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG00022 affected60 at risk
EG0018 affected10 at risk
EG00218 affected21 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0010 affected10 at risk
EG0023 affected21 at risk
EG003
Headache
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0003 affected60 at risk
EG0013 affected10 at risk
EG0024 affected21 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0012 affected10 at risk
EG0025 affected21 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0008 affected60 at risk
EG0015 affected10 at risk
EG0028 affected21 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0007 affected60 at risk
EG0013 affected10 at risk
EG00210 affected21 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0008 affected60 at risk
EG0013 affected10 at risk
EG0023 affected21 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0005 affected60 at risk
EG0011 affected10 at risk
EG0026 affected21 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0012 affected10 at risk
EG0024 affected21 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0004 affected60 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0003 affected60 at risk
EG0012 affected10 at risk
EG0022 affected21 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0002 affected60 at risk
EG0010 affected10 at risk
EG0022 affected21 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0022 affected21 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (16.0)
Systematic Assessment
EG0001 affected60 at risk
EG0011 affected10 at risk
EG0020 affected21 at risk
EG003
Given the small sample size in the different patient subsets, no formal hypothesis testing was performed, and all statistical analyses should be considered descriptive and hypothesis-generating only.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Point of Contact
Title
Organization
Phone
Extension
Email
Roche Trial Information Hotline
F. Hoffmann-La Roche AG
+41 61 6878333
global.trial_information@roche.com
ID
Term
D001943
Breast Neoplasms
Ancestor Terms
ID
Term
D009371
Neoplasms by Site
D009369
Neoplasms
D001941
Breast Diseases
D012871
Skin Diseases
D017437
Skin and Connective Tissue Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D017239
Paclitaxel
C485206
pertuzumab
D000080044
Ado-Trastuzumab Emtansine
Ancestor Terms
ID
Term
D043823
Taxoids
D043822
Cyclodecanes
D003516
Cycloparaffins
D006840
Hydrocarbons, Alicyclic
D006844
Hydrocarbons, Cyclic
D006838
Hydrocarbons
D009930
Organic Chemicals
D004224
Diterpenes
D013729
Terpenes
D008453
Maytansine
D018942
Macrolides
D007783
Lactones
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
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
10 subjects
FG00515 subjects
12 subjects
FG0057 subjects
0 subjects
FG0042 subjects
FG0050 subjects
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0051 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0042 subjects
FG0050 subjects
Disease Progression
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0046 subjects
FG0055 subjects
49.3
± 4.0
BG00451.7± 11.8
BG00555.1± 7.7
BG00653.2± 10.3
19
BG0033
BG00421
BG00522
BG006101
Male
BG0000
BG0010
BG0022
BG0030
BG0041
BG0050
BG0063
3
OG00422
OG00522
3
OG00422
OG00522
Any SAEs
Title
Measurements
OG0007
OG0015
OG0027
OG0032
OG0046
OG0056
Death
Title
Measurements
OG0001
OG0010
OG0022
OG0030
OG0041
OG0051
Any AEs Grade 3
Title
Measurements
OG00019
OG0015
OG00215
OG0032
OG00413
OG00513
Any AEs Grade 4
Title
Measurements
OG0000
OG0012
OG0021
OG0031
OG0046
OG0052
AEs leading to T-DM1 discontinuation
Title
Measurements
OG0003
OG0011
OG0021
OG0031
OG0042
OG0050
AEs leading to paclitaxel discontinuation
Title
Measurements
OG00020
OG0017
OG00214
OG0033
OG00413
OG00513
AEs leading to pertuzumab discontinuation
Title
Measurements
OG000NANA: Not applicable for this group
OG0011
OG002NANA: Not applicable for this group
OG0031
OG004NANA: Not applicable for this group
OG0050
OG002
Phase Ib Regimen 3
Participants received T-DM1 QW + paclitaxel QW intravenously.