A Study of Vemurafenib (Zelboraf) in Chinese Participants With BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma

Roche

Status and phase: Completed; Phase 1

Conditions: Malignant Melanoma

Treatments: Drug: Vemurafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01910181

YO28390

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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46 participants in 2 patient groups

Vemurafenib: Pharmacokinetic Cohort

Experimental group

Description:

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.

Treatment:

Drug: Vemurafenib

Vemurafenib: Expansion Cohort

Experimental group

Description:

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.

Treatment:

Drug: Vemurafenib