Phase 2
N=146
A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
Malignant Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT01378975 ↗Enrolled (actual)
146
Serious AEs
43.8%
Results posted
Aug 2016
Primary outcome: Primary: 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]) — 17.8 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Vemurafenib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jul 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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]) |
17.8 | — |
| SECONDARY 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 |
2.2; 0.0; 15.6; 17.9; 43.3; 41.1 | — |
| SECONDARY Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1 |
17.9 | — |
| SECONDARY Best Overall Response Rate Outside the Brain (Assessed by IRC) |
32.9; 22.5 | — |
| SECONDARY Duration of Response (DOR) (Assessed by Investigator and IRC) |
4.67; 6.64; 5.55; 10.74; 4.60; 6.64 | — |
| SECONDARY Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator) |
3.65; 3.71 | — |
| SECONDARY Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator ) |
3.68; 4.04 | — |
| SECONDARY Time to Development of New Brain Metastases in Responders |
14.92; 14.52 | — |
| SECONDARY Overall Survival |
8.87; 9.63 | — |
| SECONDARY Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) |
2.2; 0.0; 26.7; 23.2; 40.0; 53.6 | — |
| SECONDARY Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator) |
18.9; 17.9 | — |
| SECONDARY Percentage of Participants With Adverse Events (AE) |
97.8; 94.6 | — |
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
Data sourced from ClinicalTrials.gov (NCT01378975). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.