A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
Condition: Malignant Melanoma
MeSH terms: Melanoma; Brain Neoplasms
Intervention: Vemurafenib
Intervention description: 960 mg oral doses twice daily until disease progression, unacceptable toxicity or consent withdrawal.
Intervention MeSH terms: Vemurafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 146.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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