The primary purpose of this study is to determine the maximum tolerated dose (MTD) and preliminary safety of hydroxychloroquine (HCQ) when administered in conjunction with oral dabrafenib and trametinib (D+T) in patients with advanced BRAF mutant melanoma.
Name: Trametinib 2 mg daily
Type: DrugPhase 1/2
Name: hydroxychloroquine (HCQ)
Description: hydroxychloroquine (HCQ) is 600 mg orally every 12 hoursType: DrugPhase 1/2
Name: dabrafenib 150 mg orally twice a day
Type: DrugPhase 1/2
Description: Phase 1: Maximum tolerated dose (MTD) = a) the dose producing Dose Limiting Toxicity (DLT) in 2/6 patients, or b) the dose level below the dose which produced DLT in ≥ 2/3 patients, or in ≥ 3/6 patients
Measure: Phase 1: To determine the maximum tolerated dose Time: 5 weeksDescription: Phase 2: Progression free survival (PFS) is defined as the duration of time from start of treatment to time of first progression, death due to any cause or last patient contact alive and progression-free
Measure: Phase 2: To assess the clinical efficacy of HCQ+D+T by 1 year PFS rate. Time: 1 yearSingle Group Assignment
There are 2 SNPs
- Patients must have histologically confirmed diagnosis of Stage IV metastatic melanoma positive for BRAF V600E or V600K by a CLIA approved assay. --- V600E ---
- Patients must have histologically confirmed diagnosis of Stage IV metastatic melanoma positive for BRAF V600E or V600K by a CLIA approved assay. --- V600E --- --- V600K ---