Clinical Trials /

Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

NCT02143050

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients
  • Official Title: A Phase I/II Trial of Dabrafenib, Trametinib and Metformin Administered to Unresectable Stage IIIC and Stage IV BRAF V600E + Melanoma Patients

Clinical Trial IDs

  • ORG STUDY ID: BCC-MEL-14-01
  • NCT ID: NCT02143050

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
DabrafenibTafinlarDabrafenib, Trametinib and Metformin
TrametinibMekinistDabrafenib, Trametinib and Metformin
MetforminGlucophageDabrafenib, Trametinib and Metformin

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dabrafenib, Trametinib and MetforminExperimentalDabrafenib 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.
  • Dabrafenib
  • Trametinib
  • Metformin

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Observation of two CTCAE drug related grade 4 toxicities in six patients.
Time Frame:Duration of phase I portion, approxiately 6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:To estimate the overall survival rates.
Time Frame:Approximately 3 years
Safety Issue:
Description:Patients will be contacted every 3 months following treatment administration for up to three years to obtain survival data.
Measure:To explore the effect of other covariates on overall survival
Time Frame:3 years
Safety Issue:
Description:To identify demographic, disease and treatment related effects on overall survival.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:James Graham Brown Cancer Center

Trial Keywords

  • Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+

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