A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Vemurafenib (RO5185426) Adjuvant Therapy in Patients With Surgically Resected, Cutaneous BRAF-Mutant Melanoma at High Risk for Recurrence
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Melanoma
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 498
- Locations
- 206
- Primary Endpoint
- Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
Arms & Interventions
Cohort 1 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
Intervention: Placebo
Cohort 1 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
Intervention: Vemurafenib
Cohort 2 Vemurafenib
Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks
Intervention: Vemurafenib
Cohort 2 Placebo
Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Intervention: Placebo
Outcomes
Primary Outcomes
Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)
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)
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 Outcomes
- 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))
- Overall Survival (OS)(From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years))
- Percentage of Participants With Adverse Events(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(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(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))