Malignant Melanoma
Conditions
Brief summary
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.
Interventions
DRUGVemurafenib
Participants will receive vemurafenib at a dose of 960 mg twice daily orally.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chinese male or female participants, greater than or equal to (≥) 18 years of age * Histologically confirmed metastatic melanoma (surgically unresectable Stage IIIC or Stage IV, American Joint Committee on Cancer) * Treatment-naïve or having received prior systemic treatments for metastatic melanoma * Positive BRAF V600 mutation result determined by a designated laboratory using the Cobas 4800 BRAF V600 Mutation Test * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Previous allowed chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to study drug administration, and all associated toxicity must be resolved (to less than or equal to \[≤\] Grade 1 or baseline) * Recovery from effects of any major surgery (excluding tumor biopsy at baseline) or significant traumatic injury at least 14 days before the first dose of study treatment * Adequate hematologic, renal, and liver function as defined by protocol * Fertile men and women must use an effective method of contraception during treatment and for ≥6 months after completion of treatment as directed by their physician (in accordance with local requirements). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy greater than (\>) 3 months * Able to swallow pills
Exclusion criteria
* Active central nervous system (CNS) lesions (radiographically unstable/symptomatic lesions), except participants treated with stereotactic therapy or surgery who remain without evidence of disease progression in brain for ≥3 months and have been off corticosteroid and anticonvulsant therapy for ≥3 weeks * History of or known spinal cord compression or carcinomatous meningitis * Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study * Active squamous cell carcinoma (SCC) that has not been excised or has not yet adequately healed post excision * Pregnant or lactating women * Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate vemurafenib absorption * Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension, cerebrovascular accident or transient ischemic attack, or symptomatic pulmonary embolism * Known clinically significant active infection * History of allogeneic bone marrow transplantation or organ transplantation * Previous malignancy within the past 5 years other than adequately treated basal cell carcinoma or SCC of the skin, melanoma in-situ, and carcinoma in-situ of the cervix and/or curatively treated cancer from which the participant is currently disease-free, or any malignancy from which the participant has been continuously disease-free for at least 5 years * Previous treatment with a BRAF inhibitor (sorafenib allowed) or MEK inhibitor * Participants who have had one or more doses of vemurafenib in a previous clinical trial * Known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS)-related illness, or hepatitis B virus or hepatitis C virus (HCV) carriers (hepatitis B surface antigen-positive, HCV antibody-positive) * Received any investigational treatment within 4 weeks of study drug start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from 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). |
| Tmax of RO5185426 Following Day 21 Dose | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 | 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. |
| AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 | 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. |
| Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 | 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. |
| Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15 | Pre-dose (0 hours) 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. |
| Ctrough of RO5185426 on Day 19 | Pre-dose (0 hours) 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. |
| Ctrough of RO5185426 on Day 21 | Pre-dose (0 hours) 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. |
| Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21 | 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. |
| AUC of RO5185426 From 0 to 8 Hours on Day 21 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 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. |
| Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 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). |
| AUC of RO5185426 From 0 to 12 Hours on Day 1 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 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. |
| AUC of RO5185426 From 0 to 12 Hours on Day 21 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 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. |
| Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) 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). |
| Cmax of RO5185426 Following Day 21 Dose | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21 | 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. |
| Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1 | Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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) | 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. |
| Duration of Response According to RECIST Version 1.1 | 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) | 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. |
| Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1 | 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) | 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. |
| Progression-Free Survival (PFS) | 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) | 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. |
| Percentage of Participants Who Died | Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study | The percentage of participants who died during the study was reported. |
| Overall Survival (OS) | Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study | 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. |
| 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 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) | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 37 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Study Terminated by Sponsor | 6 |
Baseline characteristics
| Characteristic | Vemurafenib: All Participants |
|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 13.6 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 46 / 46 |
| serious Total, serious adverse events | 3 / 46 |
Outcome results
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1 | 17.9 accumulation ratio | Standard Deviation 14.1 |
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).
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1
Population: PK Population: All participants who provided evaluable data for PK analysis and did not have a significant protocol violation/deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1 | 37.54 h*μg/mL | Standard Deviation 22.31 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose | 4328.15 h*μg/mL | Standard Deviation 1844.35 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | AUC of RO5185426 From 0 to 12 Hours on Day 1 | 57.51 h*μg/mL | Standard Deviation 32.61 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | AUC of RO5185426 From 0 to 12 Hours on Day 21 | 720.31 h*μg/mL | Standard Deviation 185.8 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | AUC of RO5185426 From 0 to 8 Hours on Day 21 | 501.28 h*μg/mL | Standard Deviation 122.99 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Cmax of RO5185426 Following Day 21 Dose | 77.55 μg/mL | Standard Deviation 17.87 |
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.
Time frame: Pre-dose (0 hours) on Day 19
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Ctrough of RO5185426 on Day 19 | 65.595 μg/mL | Standard Deviation 23.645 |
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.
Time frame: Pre-dose (0 hours) on Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Ctrough of RO5185426 on Day 21 | 72.583 μg/mL | Standard Deviation 19.979 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose | 35.56 hours | Standard Deviation 18.06 |
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).
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
Population: PK Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1 | 6.93 μg/mL | Standard Deviation 3.86 |
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).
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21 | 0.02 hours^-1 | Standard Deviation 0.01 |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vemurafenib: PK Cohort | Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1 | 4.97 hours |
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.
Time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vemurafenib: PK Cohort | Tmax of RO5185426 Following Day 21 Dose | 1.00 hours |
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.
Time frame: Pre-dose (0 hours) on Day 15
Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vemurafenib: PK Cohort | Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15 | 63.000 μg/mL | Standard Deviation 23.327 |
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.
Time frame: 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)
Population: Safety Population; only participants with a previous response (assessment of CR or PR) were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vemurafenib: PK Cohort | Duration of Response According to RECIST Version 1.1 | 9.13 months |
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.
Time frame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study
Population: Safety Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vemurafenib: PK Cohort | Overall Survival (OS) | 18.7 months |
Secondary
Percentage of Participants Who Died
The percentage of participants who died during the study was reported.
Time frame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vemurafenib: PK Cohort | Percentage of Participants Who Died | 80.4 percentage of participants |
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.
Time frame: 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)
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vemurafenib: PK Cohort | 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 | 52.2 percentage of participants |
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.
Time frame: 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)
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vemurafenib: PK Cohort | Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1 | 69.6 percentage of participants |
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.
Time frame: 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)
Population: Safety Population; only participants with a previous response (assessment of CR or PR) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vemurafenib: PK Cohort | Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1 | 54.2 percentage of participants |
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.
Time frame: 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)
Population: Safety Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vemurafenib: PK Cohort | Progression-Free Survival (PFS) | 8.25 months |