Working… Menu

Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03543969
Recruitment Status : Recruiting
First Posted : June 1, 2018
Last Update Posted : September 14, 2021
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Skin Cancer Skin Melanoma Skin Carcinoma Drug: Vemurafenib Drug: Cobimetinib Early Phase 1

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma
Actual Study Start Date : June 14, 2018
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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).
Other Names:
  • Zelboraf®
  • BRAF/MEK-inhibitor

Drug: Cobimetinib
Cobimetinib will be dosed at 60 mg daily.
Other Names:
  • BRAF/MEK-inhibitor

Primary Outcome Measures :
  1. 8 Week Completion Rate [ Time Frame: At the end of the first 8 week treatment period ]
    Number of participants who reach 8 weeks with the prescribed on/off schedule without progression of disease. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures :
  1. Time to Treatment Failure [ Time Frame: Up to 5 years ]
    Time to treatment failure, defined as the time from the day of first dose of study drugs to the first day of treatment with another regimen or with the same regimen in a non-adaptive fashion.

  2. Objective Tumor Response Rate [ Time Frame: Up to 5 years ]
    Number of participants with tumor response. Response according to RECIST 1.1.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03543969

Layout table for location information
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Leticia Tetteh    813-745-4617   
Principal Investigator: Zeynep Eroglu, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Layout table for investigator information
Principal Investigator: Zeynep Eroglu, M.D. H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT03543969    
Other Study ID Numbers: MCC-19441
First Posted: June 1, 2018    Key Record Dates
Last Update Posted: September 14, 2021
Last Verified: September 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action