E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma

• Age >= 18 years
• Histologically or cytologically confirmed stage IV metastatic BRAF V600-mutated melanoma
• Documented metastasis of the primary tumor to the CNS
• BRAF-mutation melanoma tumor status will be established prior to entry based on previous BRAF-gene analysis reports from a Clinical Laboratory Improvement Act (CLIA) qualified laboratory. If a report is not available, the mutation analysis will be performed at screening on archival tissue
• At least one brain metastasis, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast =\< 3 weeks prior to registration and does not require immediate local intervention (surgery or radiosurgery)
• Asymptomatic or symptomatic CNS metastasis
• Systemic, measurable metastatic melanoma disease is allowed; leptomeningeal disease is allowed.
• Prior stereotactic radiosurgery and/or excision of brain metastases is allowed > 3 weeks before initiation of study treatment
• Prior immunotherapy for adjuvant or metastatic disease is allowed provided there is documented progression of disease following treatment
• Prior melanoma adjuvant BRAF/MEK inhibitor treatment is allowed if >= 12 months has elapsed between the end of therapy and initiation of study treatment
• Able to swallow and retain oral medication with no clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels
• Stable dose of corticosteroids for CNS metastasis is allowed if >= 7 days
• Seizures due to CNS metastases must be controlled with stable anti-epileptic treatment for >= 14 days
• Bisphosphonates and/or denosumab are allowed
• Life expectancy >= 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin (Hb) >= 9 g/dL without ongoing transfusional support (obtained =\< 15 days prior to registration)
• Absolute neutrophil count (ANC) >= 1.0 x 10\^9 cells/L without ongoing transfusional support (obtained =\< 15 days prior to registration)
• Platelets >= 75 x 10\^9 cells/L without ongoing transfusional support (obtained =\< 15 days prior to registration)
• Creatinine =\< 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance >= 50 mL/minute per the Cockcroft-Gault formula (obtained =\< 15 days prior to registration)
• Total bilirubin =\< 2 times the upper limit of normal (ULN) unless due to Gilbert's disease (obtained =\< 15 days prior to registration)
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 times ULN, or \< 5 times ULN for subjects with liver metastases (obtained =\< 15 days prior to registration)
• Negative serum pregnancy test done =\< 14 days prior to registration, for persons of childbearing potential only, defined as a female who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months)
• Willing to use contraception
• Sexually active persons of childbearing potential (PCBP) and persons able to father a child must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after the completion of study treatment
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• Ability to complete Patient Medication Diaries by themselves or with assistance
• Willingness to have institution procure previous BRAF-gene analysis report(s) from a CLIA qualified laboratory, or if a report is not available, willingness to have institution procure archived tumor sample to establish BRAF-mutational melanoma tumor status prior to study
• Ability to swallow

Exclusion Criteria:

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Urgent need of treatment to prevent acute neurologic deterioration, including urgent neurosurgery or radiotherapy
• Symptoms of uncontrolled intracranial pressure
• Symptomatic or untreated spinal cord compression
• Serious cardiac condition =\< 6 months prior to registration, such as uncontrolled arrhythmia, myocardial infarction, unstable angina, or heart disease defined by the New York Heart Association (NYHA) class III or class IV
• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment

• Uncontrolled intercurrent non-cardiac illness including, but not limited to:

  • Ongoing or active infection requiring IV antibiotic usage within the last week prior to study treatment
  • Any other conditions that would limit compliance with study requirements or confound the interpretation of study results

• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy

  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

• Any of the following, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception