This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes. Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm. This study consists of two Periods for Enrolled subjects: - Treatment Period - subjects will receive up to 12 months of treatment. - Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.
Name: Dabrafenib
Name: Trametinib
Description: The composite rate of grade 3/4 pyrexia, ospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia by 12 months in overall treated subjects
Measure: Change from baseline in composite rate of pyrexia related events Time: Baseline up to 12 monthsDescription: RFS is defined as the time from the date of first dose of the study medication to the date of disease recurrence or death due to any cause.
Measure: Relapse free survival (RFS) from the first dose to disease recurrence or death from any cause Time: Baseline up to approximately 24 monthsDescription: OS is defined as the time from date of the first dose of study medication to date of death due to any cause.
Measure: Overall Survival (OS) from the first dose to date of death due to any cause Time: Baseline up to approximately 24 monthsDescription: Percentage of patients who experienced pyrexia and required intervention
Measure: Percentage of patients who require management of pyrexia Time: Baseline up to 12 monthsDescription: Participants who permanently discontinued treatment due to any Adverse event during treatment
Measure: The percentage of participants who permanently discontinued treatment due to any Adverse event Time: Baseline up to 12 monthsDescription: QoL assessed using Function Assessment Cancer Therapy-melanoma (FACT-M) assessment tool. This includes the FACT-Melanoma subscale (FACT-M MS) questionnaire -specific subscale consists of 16 questions for Melanoma Subscale (MS) and 8 questions for Melanoma Surgery Scale (MSS).Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Total Score (FACT-M TS) ranges from 0 to 172 and is derived as follows: FACT-M TS= PWB Score + SWB Score + EWB Score + FWB Score + MS Score. Higher scores represent a better quality of life.
Measure: Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M MS) Time: Baseline up to 24 monthsAllocation: N/A
Single Group Assignment
There is one SNP
Higher scores represent a better quality of life.. Inclusion Criteria: - Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] - V600E/K mutation positive using a validated local test - Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. --- V600E ---
Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ - History or current evidence of cardiovascular risk - A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy Inclusion Criteria: - Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] - V600E/K mutation positive using a validated local test - Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. --- V600E ---