DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing) A Phase III Trial
This randomized phase III trial studies how well initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib works and compares it to initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab in treating patients with stage III-IV melanoma that contains a mutation known as BRAFV600 and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Dabrafenib and trametinib may block tumor growth by targeting the BRAFV600 gene. It is not yet known whether treating patients with ipilimumab and nivolumab followed by dabrafenib and trametinib is more effective than treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.
•Patients must have unresectable stage III or stage IV disease. Patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive
•Patients must have measurable disease; all sites of disease must be evaluated within 4 weeks prior to randomization
•Patients with uveal melanoma are not eligible for this trial
•Patients must have BRAF V600 mutation, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Act (CLIA)-certified lab; if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test, Foundation Medicine)
•Patients may have had prior systemic therapy in the adjuvant setting; however this adjuvant treatment must not have included a CTLA4 or PD1 pathway blocking antibody or a BRAF/MEK inhibitor; also, patients may not have had any prior systemic treatment for advanced (measurable metastatic) disease. The following are prohibited while on treatment in this study: Other anti-cancer therapies, Other investigational drugs, Patients taking any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible
•Patients must have discontinued chemotherapy, immunotherapy or other investigational agents used in the adjuvant setting >= 4 weeks prior to entering the study and recovered from adverse events due to those agents; mitomycin and nitrosoureas must have been discontinued at least 6 weeks prior to entering the study; patients must have discontinued radiation therapy >= 1 weeks prior to entering the study and recovered from any adverse events associated with treatment; prior surgery must be >= 2 weeks from registration and patients must be fully recovered from post-surgical complications
•Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients must not have taken any steroids =< 10 days prior to randomization for the purpose of managing their brain metastases; Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast
•Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. Patients must not have a history of or evidence of cardiovascular risks. Patients must not have conditions that would interfere with the ingestion or absorption of dabrafenib or trametinib
Alison Conlin, M.D.
The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.