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This open-label, multicenter study will evaluate the pharmacokinetics, safety and efficacy of vemurafenib in Chinese participants with BRAF V600 mutation-positive unresectable or metastatic melanoma. Participants will receive vemurafenib 960 milligrams (mg) orally twice daily until disease progression or unacceptable toxicity occurs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vemurafenib: Pharmacokinetic Cohort | Experimental | Participants will receive vemurafenib orally as 960 mg twice daily on Days 1 to 21 (morning dose only on Day 21), with a drug holiday from Days 22 to 27, and from Day 28 until progression, unacceptable toxicity, consent withdrawal, decision by the investigator or Sponsor, or protocol/eligibility violation. |
|
| Vemurafenib: Expansion Cohort | Experimental | Participants will receive vemurafenib orally as 960 mg twice daily from Day 1 until progression, unacceptable toxicity, consent withdrawal, decision by the investigator or Sponsor, or protocol/eligibility violation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vemurafenib | Drug | Participants will receive vemurafenib at a dose of 960 mg twice daily orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in hours by micrograms per milliliter (h*μg/mL). | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1 |
| AUC of RO5185426 From 0 to 8 Hours on Day 21 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 21 |
| AUC of RO5185426 From 0 to 12 Hours on Day 1 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 12 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1 |
| AUC of RO5185426 From 0 to 12 Hours on Day 21 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 12 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 21 |
| Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1 | Plasma PK samples were obtained from each participant, and the maximum observed post-dose concentration was recorded. The value was averaged among all participants and expressed in micrograms per milliliter (μg/mL). | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease from Baseline in sum diameter of target lesions. The percentage of participants with a best overall response of CR or PR during the study was reported. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | 100142 | China | |||
| Sun Yet-sen University Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29724167 | Derived | Si L, Zhang X, Xu Z, Jiang Q, Bu L, Wang X, Mao L, Zhang W, Richie N, Guo J. Vemurafenib in Chinese patients with BRAFV600 mutation-positive unresectable or metastatic melanoma: an open-label, multicenter phase I study. BMC Cancer. 2018 May 3;18(1):520. doi: 10.1186/s12885-018-4336-3. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Vemurafenib: All Participants | Participants were entered into the study into one of two cohorts. Vemurafenib was administered orally as 960 milligrams (mg) twice daily until progression, unacceptable toxicity, consent withdrawal, decision by the investigator or Sponsor, or protocol/eligibility violation. The Pharmacokinetic (PK) Cohort received treatment on Days 1 to 21 (morning dose only on Day 21), with a drug holiday from Days 22 to 27, and resumed treatment on Day 28. The Expansion Cohort received the same regimen from Day 1 onward, without a drug holiday. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population: All participants who received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Vemurafenib: All Participants | Participants were entered into the study into one of two cohorts. Vemurafenib was administered orally as 960 mg twice daily until progression, unacceptable toxicity, consent withdrawal, decision by the investigator or Sponsor, or protocol/eligibility violation. The PK Cohort received treatment on Days 1 to 21 (morning dose only on Day 21), with a drug holiday from Days 22 to 27, and resumed treatment on Day 28. The Expansion Cohort received the same regimen from Day 1 onward, without a drug holiday. |
| 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 | Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in hours by micrograms per milliliter (h*μg/mL). | PK Population: All participants who provided evaluable data for PK analysis and did not have a significant protocol violation/deviation. | Posted | Mean | Standard Deviation | h*μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1 |
|
Baseline until up to 28 days of last dose
Safety Population.
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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 | Vemurafenib: All Participants | Participants were entered into the study into one of two cohorts. Vemurafenib was administered orally as 960 mg twice daily until progression, unacceptable toxicity, consent withdrawal, decision by the investigator or Sponsor, or protocol/eligibility violation. The PK Cohort received treatment on Days 1 to 21 (morning dose only on Day 21), with a drug holiday from Days 22 to 27, and resumed treatment on Day 28. The Expansion Cohort received the same regimen from Day 1 onward, without a drug holiday. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Uveitis | Eye 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 | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 20, 2015 | Apr 16, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D000077484 | Vemurafenib |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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|
| Cmax of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant, and the maximum observed post-dose concentration was recorded. The value was averaged among all participants and expressed in μg/mL. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
| Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1 | Plasma PK samples were obtained from each participant, and the time of maximum post-dose concentration was recorded. The median value was derived from all participants and expressed in hours. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1 |
| Tmax of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant, and the time of maximum post-dose concentration was recorded. The median value was derived from all participants and expressed in hours. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
| AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 168 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
| Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant for calculation of t1/2, defined as the time elapsed for plasma concentrations to drop by half. The value was averaged among all participants and expressed in hours. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
| Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15 | Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL. | Pre-dose (0 hours) on Day 15 |
| Ctrough of RO5185426 on Day 19 | Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL. | Pre-dose (0 hours) on Day 19 |
| Ctrough of RO5185426 on Day 21 | Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL. | Pre-dose (0 hours) on Day 21 |
| Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The AUC on Day 21 was divided by the AUC for Day 1. The resulting value was averaged among all participants and expressed as the accumulation ratio. | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21 |
| Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21 | Plasma PK samples were obtained from each participant and the kel was estimated. The value was averaged among all participants and expressed in inverse hours (h^-1). | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
| Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression (up to 16 months as of data cutoff 15-Dec-2014) |
| Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm. PR was defined as ≥30) decrease from Baseline in sum diameter of target lesions. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). The percentage of participants who died or progressed after CR or PR was reported. | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
| Duration of Response According to RECIST Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm. PR was defined as ≥30) decrease from Baseline in sum diameter of target lesions. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). Duration of response was defined as the time from initial response of CR or PR to the first event of disease progression or death. Median time to event was estimated using Kaplan-Meier analysis, and the 95% confidence interval (CI) was estimated using the Brookmeyer-Crowley method. | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
| Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). The percentage of participants with death or disease progression during the study was reported. | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
| Progression-Free Survival (PFS) | Tumor response was evaluated using RECIST version 1.1 criteria. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). PFS was defined as the time from treatment start to the first event of disease progression or death. Median time to event was estimated using Kaplan-Meier analysis, and the 95% CI was estimated using the Brookmeyer-Crowley method. | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
| Percentage of Participants Who Died | The percentage of participants who died during the study was reported. | Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study |
| Overall Survival (OS) | OS was defined as the time from treatment start to death from any cause. Median time to event was estimated using Kaplan-Meier analysis, and the 95% CI was estimated using the Brookmeyer-Crowley method. | Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study |
| Guangzhou |
| 510060 |
| China |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | AUC of RO5185426 From 0 to 8 Hours on Day 21 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | h*μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 21 |
|
|
|
| Primary | AUC of RO5185426 From 0 to 12 Hours on Day 1 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 12 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | h*μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1 |
|
|
|
| Primary | AUC of RO5185426 From 0 to 12 Hours on Day 21 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 12 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | h*μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 21 |
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1 | Plasma PK samples were obtained from each participant, and the maximum observed post-dose concentration was recorded. The value was averaged among all participants and expressed in micrograms per milliliter (μg/mL). | PK Population. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1 |
|
|
|
| Primary | Cmax of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant, and the maximum observed post-dose concentration was recorded. The value was averaged among all participants and expressed in μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
|
|
|
| Primary | Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1 | Plasma PK samples were obtained from each participant, and the time of maximum post-dose concentration was recorded. The median value was derived from all participants and expressed in hours. | PK Population. | Posted | Median | Full Range | hours | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1 |
|
|
|
| Primary | Tmax of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant, and the time of maximum post-dose concentration was recorded. The median value was derived from all participants and expressed in hours. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Median | Full Range | hours | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
|
|
|
| Primary | AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 168 hours, using the linear trapezoid rule. The value was averaged among all participants and expressed in h*μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | h*μg/mL | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
|
|
|
| Primary | Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose | Plasma PK samples were obtained from each participant for calculation of t1/2, defined as the time elapsed for plasma concentrations to drop by half. The value was averaged among all participants and expressed in hours. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | hours | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
|
|
|
| Primary | Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15 | Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose (0 hours) on Day 15 |
|
|
|
| Primary | Ctrough of RO5185426 on Day 19 | Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose (0 hours) on Day 19 |
|
|
|
| Primary | Ctrough of RO5185426 on Day 21 | Plasma PK samples were obtained from each participant, and the concentration immediately prior to drug administration was recorded. The value was averaged among all participants and expressed in μg/mL. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose (0 hours) on Day 21 |
|
|
|
| Primary | Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1 | Plasma PK samples were obtained from each participant for calculation of AUC from 0 to 8 hours, using the linear trapezoid rule. The AUC on Day 21 was divided by the AUC for Day 1. The resulting value was averaged among all participants and expressed as the accumulation ratio. | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | accumulation ratio | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21 |
|
|
|
| Primary | Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21 | Plasma PK samples were obtained from each participant and the kel was estimated. The value was averaged among all participants and expressed in inverse hours (h^-1). | PK Population; only participants who provided sufficient data for the designated timeframe/visit were included. | Posted | Mean | Standard Deviation | hours^-1 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 |
|
|
|
| Secondary | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease from Baseline in sum diameter of target lesions. The percentage of participants with a best overall response of CR or PR during the study was reported. | Safety Population. | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression (up to 16 months as of data cutoff 15-Dec-2014) |
|
|
|
| Secondary | Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm. PR was defined as ≥30) decrease from Baseline in sum diameter of target lesions. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). The percentage of participants who died or progressed after CR or PR was reported. | Safety Population; only participants with a previous response (assessment of CR or PR) were included. | Posted | Number | percentage of participants | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
|
|
|
| Secondary | Duration of Response According to RECIST Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm. PR was defined as ≥30) decrease from Baseline in sum diameter of target lesions. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). Duration of response was defined as the time from initial response of CR or PR to the first event of disease progression or death. Median time to event was estimated using Kaplan-Meier analysis, and the 95% confidence interval (CI) was estimated using the Brookmeyer-Crowley method. | Safety Population; only participants with a previous response (assessment of CR or PR) were included. | Posted | Median | 95% Confidence Interval | months | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
|
|
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| Secondary | Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1 | Tumor response was evaluated using RECIST version 1.1 criteria. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). The percentage of participants with death or disease progression during the study was reported. | Safety Population. | Posted | Number | percentage of participants | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
|
|
|
| Secondary | Progression-Free Survival (PFS) | Tumor response was evaluated using RECIST version 1.1 criteria. Disease progression was defined as ≥20% increase on-study in sum diameter of target lesions with absolute increase ≥5 mm, or the appearance of new lesion(s). PFS was defined as the time from treatment start to the first event of disease progression or death. Median time to event was estimated using Kaplan-Meier analysis, and the 95% CI was estimated using the Brookmeyer-Crowley method. | Safety Population. | Posted | Median | 95% Confidence Interval | months | Tumor assessments at Screening, Day 1 of Cycle 3, and every two cycles (cycle length of 28 days) thereafter until disease progression; survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014) |
|
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| Secondary | Percentage of Participants Who Died | The percentage of participants who died during the study was reported. | Safety Population. | Posted | Number | percentage of participants | Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study |
|
|
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| Secondary | Overall Survival (OS) | OS was defined as the time from treatment start to death from any cause. Median time to event was estimated using Kaplan-Meier analysis, and the 95% CI was estimated using the Brookmeyer-Crowley method. | Safety Population. | Posted | Median | 95% Confidence Interval | months | Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study |
|
|
|
| 3 |
| 46 |
| 46 |
| 46 |
| Chest discomfort | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Subarachnoid hemorrhage | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Amylase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood albumin decreased | 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 |
|
| Blood bilirubin unconjugated increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Low density lipoprotein increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Protein total decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Total bile acids increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Urobilinogen urine increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Musculoskeletal disorder | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.1) | Non-systematic Assessment |
|
| Haemoglobinuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hair texture abnormal | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Palmer-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Pigmentation disorder | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system 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 |
|
| Gingival pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gingival ulceration | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Gingivitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Protein urine present | Investigations | MedDRA (17.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| Sulfur Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |