This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Hydroxychloroquine may cause cell death in tumor cells that rely on a process called "autophagy" for survival. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with dabrafenib and trametinib may work better than dabrafenib and trametinib alone to shrink and stabilize the cancer.
Name: Dabrafenib Mesylate
Name: Hydroxychloroquine Sulfate
Name: Placebo Administration
Name: Trametinib Dimethyl Sulfoxide
Description: Estimated from the Kaplan-Meier curves and compared by treatment arm. A test statistic of the difference in one-year PFS rates divided by the square root or the sum of the variances will be used with a normal approximation. Progression will be evaluated based on international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
Measure: Progression-free survival (PFS) rate Time: From randomization to progression or death (whichever occurs first), assessed at 1 year after completion of treatmentDescription: Will be estimated using the method of Kaplan-Meier by treatment arm and compared using the log-rank test. In this analysis, all cases with PFS assessed (including cases with censored < one-year) will be included. Progression will be evaluated based on international criteria proposed by the revised RECIST guideline (version 1.1).
Measure: PFS distribution Time: From randomization to progression or death (whichever occurs first), assessed at 1 year after completion of treatmentDescription: Will be estimated by treatment arm and 95% confidence intervals (CIs) will be provided. Response will be defined by the RECIST guidelines (version 1.1).
Measure: Overall response rate Time: Up to 1 year after completion of treatmentDescription: Will be estimated by treatment arm and 95% CIs will be provided. Response will be defined by the RECIST guidelines (version 1.1).
Measure: Complete response rate Time: Up to 1 year after completion of treatmentDescription: Overall survival will be described using the method of Kaplan-Meier by treatment arm.
Measure: Overall survival Time: From randomization to death from any cause, assessed up to 1 year after completion of treatmentDescription: Will be monitored carefully throughout the study and will be summarized by treatment arm. Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Measure: Incidence of adverse events Time: Up to 1 year after completion of treatmentDescription: Will be estimated by treatment arm.
Measure: Treatment duration Time: Up to 1 year after completion of treatmentAllocation: Randomized
Parallel Assignment
There are 2 SNPs
The BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Study: A Randomized Double Blind Phase II Study of Dabrafenib and Trametinib With or Without Hydroxychloroquine in Advanced BRAF V600E/K Melanoma. --- V600E ---
Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. --- V600E ---
Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. --- V600E --- --- V600E ---
Will be estimated by treatment arm.. Inclusion Criteria: - Patient must have locally advanced unresectable stage IIIC or stage IV melanoma - Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay - Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. --- V600E ---
phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) within 4 weeks prior to randomization - Patient must not have a current use of a prohibited medication Inclusion Criteria: - Patient must have locally advanced unresectable stage IIIC or stage IV melanoma - Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay - Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. --- V600E ---
Will be estimated by treatment arm.. Inclusion Criteria: - Patient must have locally advanced unresectable stage IIIC or stage IV melanoma - Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay - Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. --- V600E --- --- V600K ---
phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) within 4 weeks prior to randomization - Patient must not have a current use of a prohibited medication Inclusion Criteria: - Patient must have locally advanced unresectable stage IIIC or stage IV melanoma - Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay - Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. --- V600E --- --- V600K ---