Melanoma (patients with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma or patients with Stage IIIC cutaneous melanoma) MedDRA version: 20.0 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classifi
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female patients age = 18 years •Patients with completely resected, histologically confirmed, Stage IIC or Stage III, cutaneous melanoma where the BRAFV600 mutation status of the current primary tumor or involved lymph node is determined to be positive using the cobas® BRAF V600 Mutation Test. Patients with Stage IIIA disease must have at least one lymph node metastasis measuring > 1 mm in diameter •ECOG performance status of 0 or 1 •Life expectancy of at least 5 years •Adequate hematologic, liver, and renal function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 373 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 102
Exclusion criteria
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 radiotherapy for the treatment of melanoma •Invasive malignancy other than melanoma at the time of enrollment or within 5 years prior to first study drug administration except for adequately treated (with curative intent) basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer. This requires that the patient pathology evaluation of the screening Papanicolaou (Pap) smear, and of any polyps resected at the screening coloscopy, is negative for invasive malignancy. •Known personal history of more than three (>3) adenomatous colorectal polyps or a personal history of adenomatous colorectal polyp(s) > 2 cm in size. This also applies to the screening colonoscopy for select patients. •History of or current clinical, radiographic, or pathologic evidence of in-transit metastases, satellite, or microsatellite lesions or recurrent lymph node involvement after resection of a primary melanoma with lymph node involvement at any time in the past •History or current radiographic or pathologic evidence of distant metastases •History of clinically significant cardiac dysfunction including serious arrhythmias requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months prior to randomization, and history of congenital long QT syndrome or QTc interval > 450 ms at baseline •Current, recent (within 28 days prior to randomization) or planned use of any investigational product outside of this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of vemurafenib adjuvant treatment administered over a 52-week period in patients with completely resected BRAFV600 mutation–positive, cutaneous melanoma, as measured by DFS; Secondary Objective: • To evaluate the efficacy of vemurafenib adjuvant treatment administered over a 52-week period, as measured by OS • To evaluate the efficacy of vemurafenib adjuvant treatment administered over a 52-week period, as measured by DMFS • To evaluate the safety and tolerability of vemurafenib in the adjuvant setting • To assess quality of life as measured by EORTC QLQ-C30 • To describe the pharmacokinetics of vemurafenib in the adjuvant setting, assess between-patient variability of PK parameters, and explore and quantify potential covariates that may contribute to between-patient differences in PK parameters, using a population PK approach ; Primary end point(s): The primary endpoint, DFS is 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. The DFS component of melanoma recurrence will be assessed by the investigator. The DFS component of an occurrence of a new primary melanoma will be based upon the diagnosis made by a Roche-designated central pathology laboratory. For patients without a DFS event, data will be censored at the date of the last disease assessment. Details on censoring in the analysis of this endpoint are described in the Statistical Analysis Plan (SAP). For patients whose recurrence has been proven histologically, the date of melanoma recurrence will be defined as the earliest date of the scan or clinical examination that prompted the biopsy. For patients whose suspicious lesions were deemed not amenable to biopsy or for pat | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: -The OS interim analysis in each cohort will be performed at the time of the final DFS analysis for both cohorts The final OS analysis for Cohorts 1 & 2 will be performed after the occurrence of approximately 107 and 118 deaths,respectively (projected to occur at approximately Month 72 in each cohort) or at Month 72, whichever occurs first. -DMFS will be analyzed at the time of the final DFS analysis in each cohort–viz.,when approximately 190 DFS events have occurred for Cohort 1 and when approximately 146 DFS events have occurred for Cohort 2. ; Secondary end point(s): - Overall Survival: Overall Survival (OS) is defined as the time from randomization until the date of death from any cause. For patients still alive at the time of analysis, the data will be censored at the date the patient was last known to be alive. - DMFS: Distant metastasis-free survival (DMFS) is defined as the time from randomization until the date of diagnosis of distant (i.e., non-locoregional) metastasis or death from any cause. Details on censoring in the analysis of this endpoint are described in the SAP. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Croatia, Czech Republic, Estonia, France, Germany, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Serbia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed