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

Inclusion Criteria:

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