Trial Outcomes & Findings for A Study of Vemurafenib (Zelboraf) in Chinese Participants With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma (NCT NCT01910181)
NCT ID: NCT01910181
Last Updated: 2019-05-29
Results Overview
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).
COMPLETED
PHASE1
46 participants
Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1
2019-05-29
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
46
|
|
Overall Study
PK Cohort
|
20
|
|
Overall Study
Expansion Cohort
|
26
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
46
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Death
|
37
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Study Terminated by Sponsor
|
6
|
Baseline Characteristics
A Study of Vemurafenib (Zelboraf) in Chinese Participants With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
Vemurafenib: All Participants
n=46 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.
|
|---|---|
|
Age, Continuous
|
42.3 years
STANDARD_DEVIATION 13.6 • n=93 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 1Population: PK Population: All participants who provided evaluable data for PK analysis and did not have a significant protocol violation/deviation.
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).
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=20 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
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 outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
AUC of RO5185426 From 0 to 8 Hours on Day 21
|
501.28 h*μg/mL
Standard Deviation 122.99
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
AUC of RO5185426 From 0 to 12 Hours on Day 1
|
57.51 h*μg/mL
Standard Deviation 32.61
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
AUC of RO5185426 From 0 to 12 Hours on Day 21
|
720.31 h*μg/mL
Standard Deviation 185.80
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1Population: PK Population.
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).
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=20 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) of RO5185426 on Day 1
|
6.93 μg/mL
Standard Deviation 3.86
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Cmax of RO5185426 Following Day 21 Dose
|
77.55 μg/mL
Standard Deviation 17.87
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1Population: PK Population.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=20 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of RO5185426 on Day 1
|
4.97 hours
Interval 2.0 to 8.0
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Tmax of RO5185426 Following Day 21 Dose
|
1.00 hours
Interval 0.0 to 5.0
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
AUC From 0 to 168 Hours of RO5185426 Following Day 21 Dose
|
4328.15 h*μg/mL
Standard Deviation 1844.35
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=18 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Elimination Half-Life (t1/2) of RO5185426 Following Day 21 Dose
|
35.56 hours
Standard Deviation 18.06
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) on Day 15Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Trough Plasma Concentration (Ctrough) of RO5185426 on Day 15
|
63.000 μg/mL
Standard Deviation 23.327
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) on Day 19Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Ctrough of RO5185426 on Day 19
|
65.595 μg/mL
Standard Deviation 23.645
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) on Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Ctrough of RO5185426 on Day 21
|
72.583 μg/mL
Standard Deviation 19.979
|
PRIMARY outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8 hours) on Days 1 and 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=19 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
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 outcome
Timeframe: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21Population: PK Population; only participants who provided sufficient data for the designated timeframe/visit were included.
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).
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=18 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Terminal Elimination Rate Constant (Kel) of RO5185426 on Day 21
|
0.02 hours^-1
Standard Deviation 0.01
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=46 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
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
Interval 36.95 to 67.11
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=24 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
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 outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=24 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Duration of Response According to RECIST Version 1.1
|
9.13 months
Interval 7.39 to
The upper limit of 95% CI was not reached due to higher number (more than 40%) of censored observations.
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=46 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1
|
69.6 percentage of participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=46 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Progression-Free Survival (PFS)
|
8.25 months
Interval 5.65 to 10.94
|
SECONDARY outcome
Timeframe: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from studyPopulation: Safety Population.
The percentage of participants who died during the study was reported.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=46 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Percentage of Participants Who Died
|
80.4 percentage of participants
|
SECONDARY outcome
Timeframe: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from studyPopulation: Safety Population.
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.
Outcome measures
| Measure |
Vemurafenib: PK Cohort
n=46 Participants
The PK Cohort was first to recruit. Vemurafenib was administered 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.
|
|---|---|
|
Overall Survival (OS)
|
18.7 months
Interval 12.2 to 20.6
|
Adverse Events
Vemurafenib: All Participants
Serious adverse events
| Measure |
Vemurafenib: All Participants
n=46 participants at risk
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.
|
|---|---|
|
Eye disorders
Uveitis
|
2.2%
1/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
General disorders
Chest discomfort
|
2.2%
1/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Injury, poisoning and procedural complications
Subarachnoid hemorrhage
|
2.2%
1/46 • Baseline until up to 28 days of last dose
Safety Population.
|
Other adverse events
| Measure |
Vemurafenib: All Participants
n=46 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Blood and lymphatic system disorders
Leukopenia
|
26.1%
12/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Diarrhoea
|
71.7%
33/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Gingival bleeding
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Nausea
|
23.9%
11/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Toothache
|
10.9%
5/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Vomiting
|
15.2%
7/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
General disorders
Fatigue
|
41.3%
19/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
General disorders
Oedema peripheral
|
10.9%
5/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
General disorders
Pyrexia
|
32.6%
15/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Infections and infestations
Nasopharyngitis
|
19.6%
9/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Alanine aminotransferase increased
|
15.2%
7/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Amylase increased
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Aspartate aminotransferase increased
|
15.2%
7/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood albumin decreased
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood alkaline phosphatase increased
|
23.9%
11/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood bilirubin increased
|
58.7%
27/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood bilirubin unconjugated increased
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood cholesterol increased
|
58.7%
27/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood lactate dehydrogenase increased
|
19.6%
9/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Gamma-glutamyltransferase increased
|
26.1%
12/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Low density lipoprotein increased
|
17.4%
8/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Protein total decreased
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Total bile acids increased
|
26.1%
12/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Urobilinogen urine increased
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Weight decreased
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
23.9%
11/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
15.2%
7/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
17.4%
8/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
73.9%
34/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
28.3%
13/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
54.3%
25/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Renal and urinary disorders
Haemoglobinuria
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Renal and urinary disorders
Proteinuria
|
23.9%
11/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
54.3%
25/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
67.4%
31/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Hair texture abnormal
|
10.9%
5/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
10.9%
5/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Palmer-plantar erythrodysaesthesia syndrome
|
52.2%
24/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
41.3%
19/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
28.3%
13/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Dry mouth
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Dyspepsia
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Gingival pain
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Gastrointestinal disorders
Gingival ulceration
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
General disorders
Chest discomfort
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Infections and infestations
Gingivitis
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Infections and infestations
Influenza
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Infections and infestations
Pharyngitis
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Infections and infestations
Upper respiratory tract infection
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood creatine phosphokinase increased
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Blood triglycerides increased
|
10.9%
5/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
White blood cell count decreased
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Investigations
Protein urine present
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.7%
4/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Nervous system disorders
Dizziness
|
6.5%
3/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
13.0%
6/46 • Baseline until up to 28 days of last dose
Safety Population.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
10.9%
5/46 • Baseline until up to 28 days of last dose
Safety Population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER