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Phase 3 N=498 Randomized Double-blind Treatment

A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma

Melanoma

Enrolled (actual)
498
Serious AEs
13.2%
Results posted
Oct 2018
Primary outcome: 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 months — p=0.0010

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Vemurafenib (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Jun 2017

Outcome Measures

OutcomeResultp-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

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.

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01667419). 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.

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