- - Must have cytologically or histologically-confirmed unresectable melanoma that harbors
a BRAF V600 mutation determined by pyrosequencing assay or equivalent genotyping assay
in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, meeting
one of the following American Joint Committee on Cancer (AJCC) 8th edition staging
) AJCC stage IV (Tany, Nany, M1a(1), M1b(1), M1c(1) or M1d(1)); b.) AJCC
stage IIIC (at least N2b) or IIID with unresectable nodal/locoregional involvement.
- - Must have serum LDH > institutional upper limit of normal (ULN) at time of study
- - Must have adequate hepatic, renal, and bone marrow function.
There are no specific
minimum criteria for enrollment; this will at the discretion of the treating
physician, as any patient who would be considered for standard of care treatment with
these drugs may be considered for this trial.
- - Must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- - Willing to give written informed consent per institutional guidelines and must be able
and willing to adhere to dose and visit schedules.
- - Negative serum pregnancy test within 7 days prior to commencement of dosing in
- - Fertile men and women must use an effective method of contraception during treatment
and for at least 6 months after completion of treatment as directed by their
- - Treatment-naïve and previously treated patients will be included; however, patients
may not have received a BRAF or MEK inhibitor in the past 24 weeks.
- - May have received prior systemic and/or radiation therapy.
All adverse events
associated with prior systemic therapy or radiation therapy must have resolved to ≤
Grade 1 prior to start of study.
- - Must have measurable disease as defined by Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1.
- - Females who are pregnant, intend to become pregnant or are nursing.
- - Have been previously treated with BRAF/MEK inhibitor therapy in the past 24 weeks.
- - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
Patients with a baseline left ventricular ejection fraction of
less than 40% will be ineligible.
- - HIV-positive patients on combination antiretroviral therapy.
- - Untreated or uncontrolled brain metastases.
Patients with asymptomatic brain
metastases or previously treated brain metastases that are stable (i.e., not requiring
corticosteroids) at the time of study start will be eligible.
- - Previous malignancy is not an exclusion provided that the other malignancy is
considered under control, patient is not on concomitant anti-cancer drug therapy, and
target lesions from melanoma are clearly defined for response assessment.
- - Unwillingness or inability to comply with study and follow-up procedures.
- - The following foods/supplements are prohibited at least 7 days prior to initiation of
and during study treatment:St. John's wort or hyperforin (potent cytochrome P450
CYP3A4 enzyme inducer); Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme
- - Ocular:History of or evidence of retinal pathology on baseline ophthalmologic
examination that is considered a risk factor for neurosensory retinal detachment, RVO,
or neovascular macular degeneration.