A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

NCT01378975 | Completed Phase 2 Results

• 1 other identifier: MO25743
• Study Type: interventional
• Target: 146
• Locations: 10 countries
• Sites: 33

Brief Summary

This open-label, single-arm, multicenter study will evaluate the efficacy and safety in participants with metastatic melanoma who developed brain metastases. Participants may or may not have received prior systemic treatment for metastatic melanoma \[except treatment with v-raf murine sarcoma viral oncogene homolog B (BRAF) or mitogen-activated protein kinase (MEK) inhibitors\]. Participants will receive oral doses of 960 mg vemurafenib twice daily until disease progression, unacceptable toxicity or consent withdrawal.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BORR) Within Brain of Previously Untreated Participants (Assessed by Independent Review Committee [IRC] Using Modified Response Evaluation Criteria in Solid Tumors [RECIST])

  BORR assessed by IRC is defined as percentage of participants who were responders \[with best overall response (BOR) documented as confirmed complete response (CR) or partial response (PR)\]. The RECIST v1.1 criteria modified for independent review of body and brain lesions was based on current radiology practices. The modifications to RECIST v1.1 included allowing target lesions in the brain to be \>=5 mm by contrast-enhanced magnetic resonance imaging scan (in traditional RECIST v1.1 this is \>=10 mm), allowing up to 5 target lesions in the brain (in traditional RECIST v1.1 only 2 target lesions), and examining the lesions within the brain and outside the brain separately for analytical purposes. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm), PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Baseline up to the disease progression or death from any cause (approximately 4 years)

Secondary Outcomes (11)

• Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1

  Baseline up to the disease progression or death from any cause (approximately 4 years)

• Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1

  Baseline up to the disease progression or death from any cause (approximately 4 years)

• Best Overall Response Rate Outside the Brain (Assessed by IRC)

  Baseline up to the disease progression or death from any cause (approximately 4 years)

• Duration of Response (DOR) (Assessed by Investigator and IRC)

  Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years)

• Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)

  Baseline up to the disease progression or death from any cause (approximately 4 years)

Study Arms (2)

Cohort 1: Previously Untreated Participants

EXPERIMENTAL

Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.

Drug: Vemurafenib

Cohort 2: Previously treated Participants

EXPERIMENTAL

Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.

Drug: Vemurafenib

Interventions

Vemurafenib DRUG

960 mg oral doses twice daily until disease progression, unacceptable toxicity or consent withdrawal.

Cohort 1: Previously Untreated Participants; Cohort 2: Previously treated Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult participants, \>/= 18 years of age
• Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
• Measurable brain metastases, defined as lesions that were accurately measured in at least one dimension (longest diameter to be recorded) as ≥0.5 cm in the brain MRI with contrast, treated or untreated
• Participants may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
• Participants may or may not have symptoms related to their brain metastases
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Participants must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma

You may not qualify if:

• Increasing corticosteroid dose during the 7 days prior to first dose of study drug
• Leptomeningeal involvement in participants with no prior treatment for brain metastases
• Previous malignancy requiring active treatment within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix
• Concurrent administration of any anticancer therapies other than those administered in the study
• Treatment with any cytotoxic, investigational drug or targeted therapy 4 weeks prior to first dose of study drug. Radiation therapy ≤1 week prior to first administration of vemurafenib; and stereotactic radiotherapy ≤1 day prior to prior to first administration of vemurafenib
• Prior treatment with BRAF or MEK inhibitors
• Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (33)

Unknown Facility

Los Angeles, California, 90025, United States

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Aurora, Colorado, 80045, United States

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Tampa, Florida, 33612-9497, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Detroit, Michigan, 48201, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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Charlotte, North Carolina, 28204-2839, United States

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Dallas, Texas, 75246, United States

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Seattle, Washington, 98195, United States

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Wentworthville, New South Wales, 2145, Australia

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Melbourne, Victoria, 3002, Australia

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Toronto, Ontario, M4N 3M5, Canada

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Bordeaux, 33075, France

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Nice, 06202, France

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Paris, 75006, France

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Paris, 75475, France

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Essen, 45122, Germany

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Frankfurt, 60596, Germany

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Kiel, 24105, Germany

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Mannheim, 68167, Germany

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Münster, 48157, Germany

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Tübingen, 72076, Germany

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Tel Litwinsky, 52621, Israel

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Milan, Lombardy, 20133, Italy

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Siena, Tuscany, 53100, Italy

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Amsterdam, 1066 CX, Netherlands

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Groningen, 9713 GZ, Netherlands

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Pamplona, Navarre, 31008, Spain

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Barcelona, 08036, Spain

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Madrid, 28046, Spain

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Northwood, HA6 2RN, United Kingdom

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MeSH Terms

Conditions

Melanoma

Interventions

Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: June 23, 2011
• Study Start: July 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: June 25, 2025
• Results First Posted: August 1, 2016

Record last verified: 2025-06

Locations

NL (2); GB (1); IT (2); IL (1); CA (1); FR (4); ES (3); US (11); AU (2); DE (6)