Phase 3
Completed N=498
A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma
Source: ClinicalTrials.gov NCT01667419 ↗Enrolled (actual)
498
Serious AEs
13.2%
Results posted
Oct 2018
Primary outcomePrimary: Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT) — NA; 36.9; 23.1; 15.4 months — p=0.0010
◆ Published Evidence
Highly cited
216citations · ~27 / year
Adjuvant vemurafenib in resected, BRAF<sup>V600</sup> mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.
Summary
This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF mutation-positive melanoma at high risk for recurrence. Participants will be enrolled in two separate cohorts: Cohort 1 will include participants with completely resected Stage IIC, IIIA (participants with one or more nodal metastasis greater than [>] 1 millimeter [mm] in diameter), or IIIB cutaneous melanoma, as defined by the American Joint Committee on Cancer (AJCC) Classification, Version 7; Cohort 2 will include participants with Stage IIIC cutaneous melanoma, as defined by this classification scheme. Within each cohort, participants will be randomized (1:1 ratio) to receive vemurafenib or matching placebo over a 52-week period.
Linked Publications (2)
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Adjuvant vemurafenib in resected, BRAF<sup>V600</sup> mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.
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Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAF<sup>v600</sup> mutation-positive melanoma receiving adjuvant vemurafenib.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT) |
NA; 36.9; 23.1; 15.4 | 0.0010 sig |
| SECONDARY Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT |
NA; NA; 37.2; 30.7 | 0.0133 sig |
| SECONDARY Overall Survival (OS) |
NA; NA; 59.9; NA | 0.0274 sig |
| SECONDARY Percentage of Participants With Adverse Events |
99.4; 88.5; 100.0; 89.0 | — |
| SECONDARY Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score |
3.6; 3.9; 3.5; 3.4; 2.8; 1.5 | — |
| SECONDARY Plasma Concentration of Vemurafenib |
2880; 3050; 49900; 43400; 45300; 50200 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed melanoma of cutaneous origin
- Participants with BRAFV600 mutation-positive, cutaneous melanoma (either pathologic Stage IIC or Stage III according to AJCC Staging Criteria version 7 that has been completely resected
- BRAF V600 mutation status of the current primary tumor or involved lymph node determined to be positive using the cobas BRAF V600 mutation test
- Surgically rendered free of disease within 90 days of randomization
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of at least 5 years
- Fully recovered from the effects of any major surgery or significant traumatic injury prior to the first dose of study treatment
- Adequate hematologic, hepatic, and renal function
Exclusion Criteria
- History of any systemic or local therapy (e.g., chemotherapy, biologic or targeted therapy, hormonal therapy, or photodynamic therapy) for the treatment or prevention of melanoma, including interferon alpha-2b and pegylated interferon alpha-2b
- History of limb perfusion therapy
- History of radiotherapy for the treatment of melanoma
- Invasive malignancy other than melanoma at the time of enrollment or within 5 years prior to first dose of study treatment
- Family history of inherited colon cancer syndromes
- Known personal history of >3 adenomatous colorectal polyps or a personal history of adenomatous colorectal polyp(s) >2 centimeters (cm) in size
- History of or current clinical, radiographic, or pathologic evidence of in-transit metastases, satellite, or microsatellite lesions
- History of or current clinical, radiographic, or pathologic evidence of recurrent lymph node involvement after resection of a primary melanoma with lymph node involvement at any time in the past
- History of local and/or regional and/or distant melanoma recurrence
- History or current radiographic or pathologic evidence of distant metastases
- History of clinically significant cardiac or pulmonary dysfunction
- Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study treatment
- Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus
Data sourced from ClinicalTrials.gov (NCT01667419) and the linked publication. 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. Informational only — not medical advice.