- Must be 18 years of age or above. All races and ethnicities are eligible and no upper
limit of age is specified.
- Must have cytologically or histologically-confirmed unresectable melanoma that
harbors a BRAF V600 E or K mutation determined by pyrosequencing assay or equivalent
genotyping assay in a CLIA certified laboratory, meeting one of the following AJCC
staging criteria: 1.) American Joint Committee on Cancer (AJCC) stage IV (Tany, Nany,
M1a, b, or c); 2.) AJCC stage IIIB or IIIC with unresectable nodal/locoregional
- Adequate hepatic, renal, and bone marrow function with parameters obtained within 2
weeks prior to initiation of study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 2.
- Willing to give written informed consent per institutional guidelines and must be
able to adhere to dose and visit schedules.
- Negative serum pregnancy test within 7 days prior to commencement of dosing in
premenopausal women. Women of non-childbearing potential may be included without
serum pregnancy test if they are either surgically sterile or have been
postmenopausal for 1 year.
- 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-nave and previously treated patients will be included; however, patients
may not have received a BRAF, MEK or HSP90 inhibitor in the past.
- 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.
- Women who are pregnant, intend to become pregnant or are nursing.
- Previously treated with BRAF, MEK or HSP90 inhibitor therapy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
- HIV-positive patients on combination antiretroviral therapy.
- Potential participants with untreated or uncontrolled brain metastases or evidence of
leptomeningeal disease. 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.
- History of malabsorption or other condition that would interfere with absorption of
- 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 ophthalmologic examination
that is considered a risk factor for neurosensory retinal detachment, RVO (retinal
vein occlusion), or neovascular macular degeneration.
- Cardiac: History of clinically significant cardiac dysfunction.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both