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

Hoffmann-La Roche498 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

498

Conditions

Melanoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (207)

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

Outcomes

Primary Outcomes

Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)

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.

Time frame: 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)

Secondary Outcomes

Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT

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.

Time frame: 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)

Overall Survival (OS)

OS is defined as the time from randomization until the date of death from any cause.

Time frame: From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years)

Percentage of Participants With Adverse Events

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

Time frame: From randomization up to study completion or discontinuation (up until 13-July-2018, approximately 6 years)

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score

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).

Time frame: 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)

Plasma Concentration of Vemurafenib

Time frame: 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)