Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

Sponsor
University of Louisville (Other)
Overall Status
Recruiting
CT.gov ID
NCT02143050
Collaborator
James Graham Brown Cancer Center (Other)
53
2
1
141
26.5
0.2

Study Details

Study Description

Brief Summary

The main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor, Trametinib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

The study will be a single-arm, single center, uncontrolled phase I/II trial to estimate the safety of the combined treatments and then estimate the efficacy in terms of objective response rate in patients with stage IIIC and Stage IV melanoma treated with dabrafenib/trametinib and metformin.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
53 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Trial of Dabrafenib, Trametinib and Metformin Administered to Unresectable Stage IIIC and Stage IV BRAF V600E + Melanoma Patients
Study Start Date :
Sep 1, 2014
Anticipated Primary Completion Date :
Jun 1, 2024
Anticipated Study Completion Date :
Jun 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dabrafenib, Trametinib and Metformin

Dabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity.

Drug: Dabrafenib
Other Names:
  • Tafinlar
  • Drug: Trametinib
    Other Names:
  • Mekinist
  • Drug: Metformin
    Other Names:
  • Glucophage
  • Outcome Measures

    Primary Outcome Measures

    1. Observation of two CTCAE drug related grade 4 toxicities in six patients. [Duration of phase I portion, approxiately 6 months]

      During phase I, six patients will be enrolled and monitored for toxicities. If drug related deaths occur or more than two drug related CTCAE grade 4 toxicities occur the trial will be suspended. Phase II will estimate the efficacy of the drugs, enrolling 20 patients during stage 1 with an upper limit of 39 for the 2nd stage.

    2. Clinical Response Rate [6 years]

      Phase II will study the efficacy of the drugs enrolling 20 patients during stage I with an upper limit of 39 for the 2nd stage.

    Secondary Outcome Measures

    1. To estimate the overall survival rates. [Approximately 3 years]

      Patients will be contacted every 3 months following treatment administration for up to three years to obtain survival data.

    2. To explore the effect of other covariates on overall survival [3 years]

      To identify demographic, disease and treatment related effects on overall survival.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female patients > 18 years of age

    • Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or

    • Stage IV, American Joint Commission on Cancer)

    • Eastern Cooperative Oncology Group Performance Status of 0 to 2

    • Life expectancy > 3 months

    • At least 1 site of radiographically measurable disease by RECIST 1.1

    • Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:

    • Absolute neutrophil count > 1.0 x 10⁹/L

    • Platelet count > 50 x 10⁹/L

    • Hemoglobin > 8 g/dL

    • Serum creatinine < 2 x upper limit of normal

    • Total serum bilirubin < 3 x ULN

    • Serum aspartate transaminase or serum alanine transaminase < 3 x ULN, and < 4 x ULN if liver metastases are present

    • Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician

    • Pre-menopausal females and females < 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of the study drug

    • Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year

    • Before study entry, written informed consent must be obtained from the patient prior to performing any study related procedures

    Exclusion Criteria:
    • Prior treatment with Vemurafenib or Dabrafenib

    • Known hypersensitivity to Metformin or any of its components

    • Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia

    • Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures

    • Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 James Graham Brown Cancer Center-Universityof Louisville Louisville Kentucky United States 40202
    2 James Graham Brown Cancer Center Louisville Kentucky United States 40202

    Sponsors and Collaborators

    • University of Louisville
    • James Graham Brown Cancer Center

    Investigators

    • Principal Investigator: Jason A Chesney, MD, PhD, James Graham Brown Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jason Chesney, Director, James Graham Brown Cancer Center, University of Louisville
    ClinicalTrials.gov Identifier:
    NCT02143050
    Other Study ID Numbers:
    • BCC-MEL-14-01
    First Posted:
    May 20, 2014
    Last Update Posted:
    Oct 29, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Jason Chesney, Director, James Graham Brown Cancer Center, University of Louisville
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 29, 2021