Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

• Status: Recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a pilot study evaluating the feasibility of using adaptive intermittent dosing of vemurafenib and cobimetinib in BRAF mutant patients with elevated baseline lactate dehydrogenase (LDH).

The purpose of this study is to determine whether an intermittent adaptive dosing of vemurafenib and cobimetinib may be superior to standard, continuous dosing with these study drugs.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Treatments: Vemurafenib

Criteria

Inclusion Criteria:

• 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 criteria: a.) 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 enrollment.

• 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 premenopausal women.

• 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 physician.

• 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.

Exclusion Criteria:

• 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 study requirements. 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 inhibitor).

• 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.