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

Phase 3

Completed

Conditions: Melanoma

Interventions: Drug: Vemurafenib
Drug: Placebo

Registration Number: NCT01667419

Lead Sponsor: Hoffmann-La Roche

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 498

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 Vemurafenib	Vemurafenib	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 milligrams (mg) twice daily, in 28-day cycles, for up to 52 weeks
Cohort 1 Placebo	Placebo	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Cohort 2 Placebo	Placebo	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Cohort 2 Vemurafenib	Vemurafenib	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks

Primary Outcome Measures

Name	Time	Method
Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)	From randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)	DFS was defined as the time from randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT	From randomization until the date of diagnosis of distant (i.e., non-locoregional) metastases or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)	DMFS was defined as the time from randomization until the date of diagnosis of distant (i.e. non-locoregional) metastases or death from any cause.
Overall Survival (OS)	From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years)	OS is defined as the time from randomization until the date of death from any cause.
Percentage of Participants With Adverse Events	From randomization up to study completion or discontinuation (up until 13-July-2018, approximately 6 years)	An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score	Day 1, Day 8, Day 15, Day 22 of Cycle 1;Day 1, Day 15 of Cycle 2;Day 1 Cycles 3-13;end of treatment(up to 13 months);every 13 weeks thereafter until recurrence or occurrence of a new primary melanoma (up to 17-Apr-17 data cut-off,approximately 4.5 years)	European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire assesses 8 symptoms, function, financial difficulties, and a global health status/health-related quality of life (HRQoL). Most questions use a 4-point scale (1 'Not at all' to 4 'Very much';2 questions use a 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. Higher scores for the function and HRQoL represent higher levels of functioning and HRQoL, higher scores for the symptom represent higher levels of symptoms/problems, higher score for financial difficulty represent higher level of perceived financial burden of treatment. Changes of 5-10 points are considered to represent a minimally important difference to participants. A positive value means an increase, and negative value means a decrease in score at the indicated time-point relative to the score at baseline (Cycle 1 Day 1).
Plasma Concentration of Vemurafenib	Pre-morning dose (0 hour [hr]) and 1 to 4 hrs post-dose on Days 1, 8, 15, and 22 of Cycle 1; pre-morning dose (0 hr) on Days 1 and 15 of Cycle 2; pre-morning dose (0 hr) on Day 1 of Cycles 3-13; at end of treatment (up to 13 months)

Trial Locations

Locations (206): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
UCLA Department of Medicine; Division of Hematology / Oncology
🇺🇸
California City, California, United States
Kaiser Permanente - Hayward
🇺🇸
Hayward, California, United States
UCLA Hematology Oncology - Irvine
🇺🇸
Irvine, California, United States
UCSD Moores Cancer Center
🇺🇸
La Jolla, California, United States
The Angeles Clinic and Research Institute - W LA Office
🇺🇸
Los Angeles, California, United States
Cancer Center Of Santa Barbara; Network Clinical Research Specialist
🇺🇸
Los Angeles, California, United States
TRIO-US Network Administration; Network Clinical Research Specialist
🇺🇸
Los Angeles, California, United States
Kaiser Foundation Hospital - Oakland (W. MacArthur)
🇺🇸
Oakland, California, United States
Kaiser Permanente - Oakland
🇺🇸
Oakland, California, United States
Scroll for more (196 remaining)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States