Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Zeynep Eroglu, M.D.
Principal Investigator Affiliation H. Lee Moffitt Cancer Center and Research Institute
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma (Skin), Skin Cancer, Skin Melanoma, Skin Carcinoma
Study Website: View Trial Website
Additional Details

Vemurafenib and cobimetinib are already U.S. Food and Drug Administration (FDA)-approved for the treatment of BRAF-mutant metastatic melanoma; however, melanoma often develops resistance to these drugs over time, and the tumors start to re-grow. Investigators will use the participant's LDH (lactate dehydrogenase) levels obtained from routine blood work, along with CT scans to decide when to hold or resume their study treatment. Investigators hypothesize that this type of dosing schedule with vemurafenib and cobimetinib may potentially delay the time to progression and re-growth of their melanoma.

Arms & Interventions


Experimental: BRAF-MEK Inhibitor Therapy

Vemurafenib twice a day and cobimetinib daily, 3 weeks on / 2 weeks off / 3 weeks on, for an 8-week cycle. After 8 week cycle, response to these study drugs will be analyzed based on several parameters to determine if participants will proceed in the study. Participants will be invited for post-treatment follow-up visits for up to 5 years.


Drug: - Vemurafenib

Vemurafenib will be dosed at 960 mg by mouth (PO) twice a day (BID).

Drug: - Cobimetinib

Cobimetinib will be dosed at 60 mg daily.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Tampa, Florida




H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612

Site Contact

Leticia Tetteh


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