Overview

This trial is active, not recruiting.

Condition malignant melanoma
Treatment vemurafenib
Phase phase 1
Target BRAF
Sponsor Hoffmann-La Roche
Start date August 2013
End date October 2013
Trial size 46 participants
Trial identifier NCT01910181, YO28390

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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 Zelboraf
Participants will receive vemurafenib at a dose of 960 mg twice daily orally.
(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.
vemurafenib Zelboraf
Participants will receive vemurafenib at a dose of 960 mg twice daily orally.

Primary Outcomes

Measure
Area Under the Plasma Concentration-Time Curve (AUC) of RO5185426 From 0 to 8 Hours on Day 1
time frame: 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
time frame: 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
time frame: 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
time frame: 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
time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
Cmax of RO5185426 Following Day 21 Dose
time frame: 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
time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12 hours) on Day 1
Tmax of RO5185426 Following Day 21 Dose
time frame: 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
time frame: 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
time frame: 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
time frame: Pre-dose (0 hours) on Day 15
Ctrough of RO5185426 on Day 19
time frame: Pre-dose (0 hours) on Day 19
Ctrough of RO5185426 on Day 21
time frame: Pre-dose (0 hours) on Day 21
Accumulation Ratio of RO5185426 AUC From 0 to 8 Hours Between Day 21 and Day 1
time frame: 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
time frame: Pre-dose (0 hours) and post-dose (1, 2, 4, 5, 8, 12, 24, 28, 72, 76, 168 hours) from Day 21

Secondary Outcomes

Measure
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
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)
Percentage of Participants With Disease Progression or Death Among Participants With a Previous Assessment of CR or PR According to RECIST Version 1.1
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)
Duration of Response According to RECIST Version 1.1
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)
Percentage of Participants With Death or Disease Progression According to RECIST Version 1.1
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)
Progression-Free Survival (PFS)
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)
Percentage of Participants Who Died
time frame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014)
Overall Survival (OS)
time frame: Throughout treatment (up to 16 months); survival followed every 3 months until discontinuation from study (up to 16 months as of data cutoff 15-Dec-2014)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase I Open-Label, Multicenter, Multiple-Dose Study to Investigate the Pharmacokinetics, Safety, and Efficacy of Vemurafenib in Chinese Patients With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.