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Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies.
This is a phase 1a and phase 1b, open-label, dose-escalation study to evaluate the safety and tolerability of selinexor and determine the RP2D in patients with solid tumor malignancies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (Colorectal Cancer) | Experimental | Participants with colorectal cancer and liver metastasis received oral selinexor as single agent in 8 schedules, Schedule1: ≤12milligrams per meter square(mg/m^2) 3 times weekly(TIW) during Weeks 1 and 3, twice weekly(BIW) during Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule2: >12mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule3: ≥30mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle(28 days/cycle); Schedule4: ≥20mg/m^2 BIW(Days 1 and 2) up to 8 doses/cycle(28 days/cycle); Schedule5: ≥35mg/m^2 BIW(Days 1 and 4) up to 8 doses(28 days/cycle); Schedule6: ≥20mg/m^2 BIW(Days 1 and 4) after 500 mg(Week 1) to 1000 mg(Week 2 onwards) acetaminophen(given 1 hour prior to each selinexor dose) up to 8 doses/cycle (28 days/cycle); Schedule7: ≥50mg/m^2 once weekly(QW) up to 4 doses/cycle(28 days per cycle); Schedule8: ≥45mg/m^2 BIW(Days 1 and 3) up to 4 doses/cycle(21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
| Arm B (Gynecological Cancer) | Experimental | Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
| Arm C (Squamous Cell Cancer) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selinexor | Drug | Participants in this study will receive selinexor orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m^2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in 4-week (28 days for schedule 1 to 7) and 3-week (21 days for schedule 8) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria; is fatal, life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. Number of participants with TEAEs and TESAEs were reported. | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
| Number of Participants With Treatment-related Treatment-emergent Adverse Events | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A treatment-related AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product; the event had a causal relationship with the treatment or usage. | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Greater Than or Equal to Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Selinexor | Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data. | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Time of Maximum Observed Concentration in Plasma (Tmax) of Selinexor |
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Inclusion Criteria:
Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis.
Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:
Up to 12 patients with metastatic colorectal cancer with a history of progression or recurrence following prior fluoropyrimidine, irinotecan and platinum containing regimens as well as bevacizumab. In addition, patients with Kras wild type tumor must have received at least one EGFR blocker.
Up to 6 patients with histological or cytological documentation of advanced ovarian, fallopian tube, or primary peritoneal carcinoma with a history of progression or recurrence following at least one prior platinum and one taxane based chemotherapy
Up to 12 patients with incurable Squamous cell cancers as follows:
Up to 6 patients with castration-resistant prostate cancer (CRPC) that was pathologically confirmed as adenocarcinoma of the prostate and with evidence of metastatic disease on bone scan or other imaging. Patient must have progressive disease after at least one hormonal treatment and one cytotoxic therapy e.g. with docetaxel, mitoxantrone.
Up to 12 patients with unresectable metastatic melanoma whose disease progressed on at least 1 prior systemic anticancer regimen (chemotherapy, biological or immunotherapy, or targeted therapy). Enrollment to this cohort may have been stopped before reaching 12 patients once the dose-escalation portion of the study was completed.
Approximately 6 patients with advanced or metastatic solid tumors were to be enrolled on Schedule 8 at a starting dose of 35 mg/m^2 to assess general tolerability and activity of selinexor.
Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.
Both Dose Escalation and Expansion Phases: There is no upper limit on the number of prior treatments provided that all inclusion criteria are met and exclusion criteria are not met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimes.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States | ||
| Karmanos Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28630120 | Derived | Machlus KR, Wu SK, Vijey P, Soussou TS, Liu ZJ, Shacham E, Unger TJ, Kashyap T, Klebanov B, Sola-Visner M, Crochiere M, Italiano JE Jr, Landesman Y. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood. 2017 Aug 31;130(9):1132-1143. doi: 10.1182/blood-2016-11-752840. Epub 2017 Jun 19. |
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A total of 192 participants were enrolled, of which 191 participants started study (1 participant reported missing malignancy), 189 participants received at least 1 dose of study drug.
The study was conducted at six centers in United States, Canada, and Denmark from 18 June 2012 and 15 March 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (Colorectal Cancer) | Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 milligrams per meter square (mg/m^2) 3 times weekly (TIW) during Weeks 1 and 3, twice weekly (BIW) during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m^2 once weekly (QW) up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| FG001 | Arm B (Gynecological Cancer) | Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| FG002 | Arm C (Squamous Cell Cancer) | Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| FG003 | Arm D (Castrate-resistant Prostate Cancer) | Participants with CRPC received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| FG004 | Arm E (Glioblastoma Multiforme) | Participants with GBM received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| FG005 | Arm F (Melanoma) | Participants with melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| FG006 | Arm G (Other Solid Tumors) | Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population included all participants who received at least one dose of selinexor. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A (Colorectal Cancer) | Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 milligrams per meter square (mg/m^2) 3 times weekly (TIW) during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m^2 once weekly (QW) up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria; is fatal, life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. Number of participants with TEAEs and TESAEs were reported. | Safety population included all participants who received at least one dose of selinexor. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Count of Participants | Participants | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A (Colorectal Cancer) | Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jatin Shah | Karyopharm Therapeutics Inc | (617) 658-0600 | jshah@karyopharm.com |
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| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D005909 | Glioblastoma |
| D000230 | Adenocarcinoma |
| D008545 | Melanoma |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C585161 | selinexor |
| D000082 | Acetaminophen |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 |
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Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
| Arm D (Castrate-resistant Prostate Cancer) | Experimental | Participants with castrate-resistant prostate cancer (CRPC) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
| Arm E (Glioblastoma Multiforme) | Experimental | Participants with glioblastoma multiforme (GBM) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
| Arm F (Melanoma) | Experimental | Participants with Melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
| Arm G (Other Solid Tumors) | Experimental | Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
|
|
| Acetaminophen | Drug | Oral 500 mg (in Cycle 1, Week 1) to 1000 mg (in Cycle 1, Week 2 and onwards) of acetaminophen will be administered 1 hour prior to each selinexor dose up to 8 doses per cycle (28 days per cycle) |
|
| From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
| Number of Participants Who Experienced Dose Limiting Toxicity (DLT) | Evaluation of DLTs was only conducted in participants who participated in the Dose-escalation Phase. A DLT was defined as any of the following, considered possibly related to drug administration, occurring in the first 28 days (or 21 days for participants on Schedule 8) at the target dose (ie, for Schedule 2 this meant the first 4 weeks after the 12 mg/m2 run-in week): Missed selinexor doses due to drug-related toxicities, discontinuation of a participant due to a toxicity that was at least possibly related to study drug before completing Cycle 1. | Cycle 1 only (28-day cycle) |
| Recommended Phase 2 Dose (RP2D) | The RP2D was the maximum tolerated dose (MTD) or less. MTD was defined as the next lower dose level below the one in which >1 of 3 participants or ≥2 of 6 participants experienced DLT, provided that dose level was ≤25 percent (%) lower than the highest (intolerable) dose tested. If the projected MTD was >25% lower than the highest dose tested, then an additional cohort of ≥3 participants was added at a dose that was intermediate between the intolerable dose and the next lower dose. | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data. |
| Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Area Under the Concentration Time Curve From the Time of Dosing to Time in Plasma (AUC0-t) of Selinexor | AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration. | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Area Under the Concentration Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Selinexor | AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated). It was calculated as AUC0-t + Ct/kel, where: Ct = the last observed non-zero concentration and Kel = elimination rate constant. | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Elimination Half-Life (t1/2) of Selinexor | t1/2 was defined as elimination half-life, it was calculated as ln(2)/kel, where In = natural logarithm and kel = elimination rate constant. | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Apparent Total Body Clearance (CL/F) of Selinexor | CL/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram). | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Apparent Volume of Distribution of Selinexor (Vd/F) | Vd/F was calculated as Dose/(kel * AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram). | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
| Number of Participants With Best Overall Response (BOR) | BOR is response recorded from start of treatment until disease progression/recurrence. Best lesion response was defined by Recist Criteria V1 (for target and non-target lesions) and RANO criteria (for glioblastoma multiforme): complete response (CR)- disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to less than (<) 10 mm; partial response (PR)- at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum longest diameter; stable disease (SD)- steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; progressive disease (PD): at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded since treatment started. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm, or appearance of one or more new lesions. | Up to maximum duration of 45 months |
| Percentage of Participants With Objective Response | Objective response rate (ORR) was determined as percentage of participants who had either CR or PR, as defined by RECIST v1.1 (for solid tumors). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to <10 mm and PR was defined as at least 30% decrease in sum of diameters of target lesions. ORR was calculated as a proportion and included a 2 sided 95% CI using the exact (Clopper-Pearson) method. | Up to maximum duration of 45 months |
| Duration of Stable Disease (SD) | Duration of stable disease was defined as the time from the date of first dose to first documented radiologic evidence of disease recurrence or progression, as defined by RECIST v1.1 (for solid tumors) or RANO criteria (for GBM and AnaA). | From first dose of study drug administration to first documented evidence of disease recurrence or progression (maximum duration of 45 months) |
| Progression-free Survival (PFS) | Progression-free survival was calculated from the date of first dose of study treatment to first documented evidence of disease recurrence or progression or death due to any cause. Patients who are last known to be alive and without evidence of progression will be censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, patients are censored at the time of last evaluable disease assessment prior to the missed assessment. Progressive disease was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease. | From start of study drug administration until PD or discontinuation from the study or death (maximum duration of 45 months) |
| Overall Survival (OS) | OS was calculated from the date of first dose to date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, were censored at the day they were last known to be alive. The OS was calculated using the Kaplan-Meier method. | From first dose of study drug administration to date of death (maximum duration of 45 months) |
| Detroit |
| Michigan |
| 48201 |
| United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
| Gabrail Cancer Center | Canton | Ohio | 44718 | United States |
| Princess Margaret Hospital | Toronto | Ontario | M5T 2M9 | Canada |
| Rigshospitalet | Copenhagen | 2100 | Denmark |
| Incidence or severity of AEs |
|
| Disease progression |
|
| Non-compliance with study procedures |
|
| Death |
|
| Other treatments become available |
|
| Investigator discretion |
|
| Other |
|
| Randomized but not treated |
|
| BG001 | Arm B (Gynecological Cancer) | Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| BG002 | Arm C (Squamous Cell Cancer) | Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| BG003 | Arm D (Castrate-resistant Prostate Cancer) | Participants with CRPC received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| BG004 | Arm E (Glioblastoma Multiforme) | Participants with GBM received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| BG005 | Arm F (Melanoma) | Participants with melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| BG006 | Arm G (Other Solid Tumors) | Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| BG007 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Arm A (Colorectal Cancer) | Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| OG001 | Arm B (Gynecological Cancer) | Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| OG002 | Arm C (Squamous Cell Cancer) | Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| OG003 | Arm D (Castrate-resistant Prostate Cancer) | Participants with CRPC received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| OG004 | Arm E (Glioblastoma Multiforme) | Participants with GBM received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| OG005 | Arm F (Melanoma) | Participants with melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| OG006 | Arm G (Other Solid Tumors) | Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
|
|
| Primary | Number of Participants With Treatment-related Treatment-emergent Adverse Events | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A treatment-related AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product; the event had a causal relationship with the treatment or usage. | Safety population included all participants who received at least one dose of selinexor. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Count of Participants | Participants | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
|
|
|
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Greater Than or Equal to Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. | Safety population included all participants who received at least one dose of selinexor. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Count of Participants | Participants | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
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| Primary | Number of Participants Who Experienced Dose Limiting Toxicity (DLT) | Evaluation of DLTs was only conducted in participants who participated in the Dose-escalation Phase. A DLT was defined as any of the following, considered possibly related to drug administration, occurring in the first 28 days (or 21 days for participants on Schedule 8) at the target dose (ie, for Schedule 2 this meant the first 4 weeks after the 12 mg/m2 run-in week): Missed selinexor doses due to drug-related toxicities, discontinuation of a participant due to a toxicity that was at least possibly related to study drug before completing Cycle 1. | DLT Evaluable Population included all participants enrolled to the study during the dose-escalation phase who met the inclusion/exclusion criteria on first day of dosing and completed at least 1 cycle of therapy or experienced a DLT during the first cycle. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Count of Participants | Participants | Cycle 1 only (28-day cycle) |
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| Primary | Recommended Phase 2 Dose (RP2D) | The RP2D was the maximum tolerated dose (MTD) or less. MTD was defined as the next lower dose level below the one in which >1 of 3 participants or ≥2 of 6 participants experienced DLT, provided that dose level was ≤25 percent (%) lower than the highest (intolerable) dose tested. If the projected MTD was >25% lower than the highest dose tested, then an additional cohort of ≥3 participants was added at a dose that was intermediate between the intolerable dose and the next lower dose. | Safety Population included all participants who received at least one dose of selinexor. The data in terms of dose was reported as combined data for participants from all arms, pre-specified in protocol. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Number | mg/m^2 | From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months) |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Selinexor | Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data. | Pharmacokinetic (PK) population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms where single participant was analyzed. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Time of Maximum Observed Concentration in Plasma (Tmax) of Selinexor | Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data. | PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and full range data was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Median | Full Range | hours | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Area Under the Concentration Time Curve From the Time of Dosing to Time in Plasma (AUC0-t) of Selinexor | AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration. | PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram hour per milliliter | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Area Under the Concentration Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Selinexor | AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated). It was calculated as AUC0-t + Ct/kel, where: Ct = the last observed non-zero concentration and Kel = elimination rate constant. | PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram hour per milliliter | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Elimination Half-Life (t1/2) of Selinexor | t1/2 was defined as elimination half-life, it was calculated as ln(2)/kel, where In = natural logarithm and kel = elimination rate constant. | PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and full range was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Median | Full Range | hours | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Apparent Total Body Clearance (CL/F) of Selinexor | CL/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram). | PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour per kilogram | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Apparent Volume of Distribution of Selinexor (Vd/F) | Vd/F was calculated as Dose/(kel * AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram). | PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per kilogram | Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes |
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| Secondary | Number of Participants With Best Overall Response (BOR) | BOR is response recorded from start of treatment until disease progression/recurrence. Best lesion response was defined by Recist Criteria V1 (for target and non-target lesions) and RANO criteria (for glioblastoma multiforme): complete response (CR)- disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to less than (<) 10 mm; partial response (PR)- at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum longest diameter; stable disease (SD)- steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; progressive disease (PD): at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded since treatment started. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm, or appearance of one or more new lesions. | Efficacy Population included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Count of Participants | Participants | Up to maximum duration of 45 months |
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| Secondary | Percentage of Participants With Objective Response | Objective response rate (ORR) was determined as percentage of participants who had either CR or PR, as defined by RECIST v1.1 (for solid tumors). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to <10 mm and PR was defined as at least 30% decrease in sum of diameters of target lesions. ORR was calculated as a proportion and included a 2 sided 95% CI using the exact (Clopper-Pearson) method. | Efficacy Population included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Number | percentage of participants | Up to maximum duration of 45 months |
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| Secondary | Duration of Stable Disease (SD) | Duration of stable disease was defined as the time from the date of first dose to first documented radiologic evidence of disease recurrence or progression, as defined by RECIST v1.1 (for solid tumors) or RANO criteria (for GBM and AnaA). | Efficacy Population included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Median | 95% Confidence Interval | Days | From first dose of study drug administration to first documented evidence of disease recurrence or progression (maximum duration of 45 months) |
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|
|
| Secondary | Progression-free Survival (PFS) | Progression-free survival was calculated from the date of first dose of study treatment to first documented evidence of disease recurrence or progression or death due to any cause. Patients who are last known to be alive and without evidence of progression will be censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, patients are censored at the time of last evaluable disease assessment prior to the missed assessment. Progressive disease was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease. | Efficacy Population included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Median | 95% Confidence Interval | Days | From start of study drug administration until PD or discontinuation from the study or death (maximum duration of 45 months) |
|
|
|
| Secondary | Overall Survival (OS) | OS was calculated from the date of first dose to date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, were censored at the day they were last known to be alive. The OS was calculated using the Kaplan-Meier method. | Efficacy Population included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented. | Posted | Median | 95% Confidence Interval | Days | From first dose of study drug administration to date of death (maximum duration of 45 months) |
|
|
|
| 30 |
| 59 |
| 59 |
| 59 |
| EG001 | Arm B (Gynecological Cancer) | Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. | 13 | 20 | 20 | 20 |
| EG002 | Arm C (Squamous Cell Cancer) | Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. | 9 | 21 | 21 | 21 |
| EG003 | Arm D (Castrate-resistant Prostate Cancer) | Participants with CRPC received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. | 8 | 21 | 21 | 21 |
| EG004 | Arm E (Glioblastoma Multiforme) | Participants with GBM received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. | 2 | 6 | 6 | 6 |
| EG005 | Arm F (Melanoma) | Participants with melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. | 5 | 15 | 15 | 15 |
| EG006 | Arm G (Other Solid Tumors) | Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. | 24 | 47 | 46 | 47 |
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Large intestinal stenosis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Death | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Intracardiac thrombus | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Large intestine perforation | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bile duct stenosis | Hepatobiliary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Biliary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Osteomyelitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pulmonary function test decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.1) | Non-systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.1) | Non-systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cerebellar syndrome | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cerebral thrombosis | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Facial paresis | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pulmonary thrombosis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Superior vena cava syndrome | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Venous thrombosis | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Macular degeneration | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Night blindness | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Large intestinal stenosis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Oral mucosa haematoma | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Face oedema | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Device occlusion | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Dermatitis infected | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Cystitis radiation | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Procedural anxiety | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Radiation proctitis | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Amylase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Metabolic alkalosis | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Kyphosis | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.1) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Myoclonus | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Restless legs syndrome | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Mental disorder | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract pain | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Renal colic | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Renal pain | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Urinary tract disorder | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Coital bleeding | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Koilonychia | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Immobile | Social circumstances | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Infarction | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
Not provided
Not provided
| D018307 |
| Neoplasms, Squamous Cell |
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |
| D018358 | Neuroendocrine Tumors |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| Aniline Compounds |
| D000588 | Amines |
| Participants with Treatment-related TESAEs |
|
| Partial Response |
|
| Stable Disease |
|
| Progression (Objective) |
|
| Progressive Disease due to symptomatic deterioration |
|
| Not Evaluable |
|