Molecularly Targeted Therapy in Treating Patients With BRAF Wild-type Melanoma That is Metastatic

Inclusion Criteria

• Patient with metastatic or locally advanced and unresectable BRAF wild-type melanoma who have either progressed following previous treatment of immunotherapy, or are not eligible for immunotherapy; pts. are defined as "BRAF wild-type" if they test negative for V600 mutations based on a Clinical Laboratory Improvement Amendments (CLIA) certified assay
• Patients must have tumor accessible by interventional radiology or surgical intervention and suitable for biopsy (BX) with 5-6 passes of a 16 or 18 gauge needle for core BX (defined as at least 1 cm^3 tumor/50 mg accessible for BX), and must agree to undergo up to two surgical resections/biopsies to collect tumor for research purposes; the first of these biopsies will occur at the beginning of the study, prior to genetic analysis and Rx; the second BX will be performed at the time of DZ progression/end of study should funding be available
• Patients must have measurable DZ (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 [v1.1] criteria), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam; for lymph nodes, the short axis must be >= 15 mm
• Previous therapies: prior radiation therapies, immunotherapies, and investigational therapies are allowed as follows.
• Radiation: prior radiation therapy (RT) is allowed with the following conditions:
• Patients who have received minimal RT (= = 2 weeks prior to the initiation of study Rx
• Patients who have received RT that constituted > 5% but = 4 weeks prior to the initiation of study treatment
• Patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
• Patients may be biopsied while undergoing RT as long as BX site is not in the radiation portal; however, they still have to wait the required amount of time from radiation to treatment even though the tumor board may have already occurred and a treatment plan assigned
• Other therapies: prior investigational or targeted therapies and immunotherapies may be allowed following discussion with the PI (PI); if the PI deems the prior treatment acceptable, patients must not have received these therapies for 28 days or five half-lives of the drug (whichever is lesser) prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies; prior therapy with mitogen-activated protein kinase (MEK) inhibitors will not be allowed
• Patients with chronic grade 2 toxicity may be eligible at the discretion of the PI if the condition has been stable, and not worsening, for at least 30 days; pts. with ongoing alopecia of any grade will be eligible
• Patient must have a life expectancy of >= 3 months, as estimated by the treating oncologist
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status = = 9 g/dL
• Leukocytes >= 3,000/microliter (mcL)
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets (PLT) >= 100,000/mcL
• Aspartate aminotransferase (AST) = = 50 mL/min/1.73 m^2 for pts. with creatinine above institutional normal
• If available, pt. must agree to provide archival tissue for research purposes (either archival paraffin tissue block or 10 unstained slides of a primary or metastatic melanoma lesion) prior to enrollment; samples should be shipped within 1 month after enrollment
• Patient agrees to having a blood sample (a minimum of 10 mL, with 20 mL preferred) drawn and analyzed to compare their normal genetic profile to that of their tumor sample
• Patient must be able to tolerate oral medication
• Women of child-bearing potential and men must agree to use 2 forms of adequate contracept