Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

Sponsor
H. Lee Moffitt Cancer Center and Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT03543969
Collaborator
(none)
20
1
1
53.6
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Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Jun 14, 2018
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

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:
  • COTELLIC®
  • BRAF/MEK-inhibitor
  • Outcome Measures

    Primary Outcome Measures

    1. 8 Week Completion Rate [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 [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 [Up to 5 years]

      Number of participants with tumor response. Response according to RECIST 1.1.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612

    Sponsors and Collaborators

    • H. Lee Moffitt Cancer Center and Research Institute

    Investigators

    • Principal Investigator: Zeynep Eroglu, M.D., H. Lee Moffitt Cancer Center and Research Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT03543969
    Other Study ID Numbers:
    • MCC-19441
    First Posted:
    Jun 1, 2018
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 2022
    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:

    Study Results

    No Results Posted as of Jul 28, 2022