A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

Roche

Status and phase: Completed; Phase 2

Conditions: Malignant Melanoma

Treatments: Drug: Vemurafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01378975

MO25743

Details and patient eligibility

About

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.

Enrollment: 146 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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146 participants in 2 patient groups

Cohort 1: Previously Untreated Participants

Experimental group

Description:

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.

Treatment:

Drug: Vemurafenib

Cohort 2: Previously treated Participants

Experimental group

Description:

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.

Treatment:

Drug: Vemurafenib