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A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients

NCT01638676

Description:

The main purpose of this study is to evaluate the safety of Vemurafenib in combination with Metformin in melanoma patients. The phase II part of the study will also evaluate the clinical activity of the combined regiment. Based on pre-clinical studies and a phase I trial, the investigators hypothesize that the combination of an FDA-approved non-toxic dose of oral Metformin with Vemurafenib 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:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients
  • Official Title: A Phase I/II Trial of Vemurafenib and Metformin to Unresectable Stage IIIC and Stage IV BRAF.V600E+ Melanoma Patients

Clinical Trial IDs

  • ORG STUDY ID: BCC-MEL-11-03
  • NCT ID: NCT01638676

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
VemurafenibVemurafenib branded as ZelborafVemurafenib and Metformin
MetforminMetformin hydrochloride branded as GlucophageVemurafenib and Metformin

Purpose

The main purpose of this study is to evaluate the safety of Vemurafenib in combination with Metformin in melanoma patients. The phase II part of the study will also evaluate the clinical activity of the combined regiment. Based on pre-clinical studies and a phase I trial, the investigators hypothesize that the combination of an FDA-approved non-toxic dose of oral Metformin with Vemurafenib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.

Detailed Description

      This is a Phase I/II study. Phase I will be evaluating the safety of the FDA-approved
      Vemurafenib (960 mg orally, daily) in combination with Metformin (500 mg orally, twice daily
      for 2 weeks, then 850 mg orally,twice daily) in patients with unresectable Stage IIIC and
      Stage IV melanoma. Phase II will evaluate the clinical activity of the combined
      Vemurafenib/Metformin regimen. The safety profile of this combined Vemurafenib/Metformin
      regimen will be monitored during both phases. The treatment period consists of 28-day cycles
      until progression or unacceptable toxicity occurs.
    

Trial Arms

NameTypeDescriptionInterventions
Vemurafenib and MetforminExperimental
  • Vemurafenib
  • Metformin

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients ≥ 18 years of age;

          2. Patients with histological confirmed BRAFV600E melanoma (Stage IIIC or Stage IV,
             American Joint Commission on Cancer);

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 2;

          4. Life expectancy ≥ 3 months;

          5. At least 1 site of radiographically measurable disease by RECIST 1.1

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

               -  Absolute neutrophil count (ANC) ≥ 1.0 x 109/L;

               -  Platelet count ≥ 50 x 109/L;

               -  Hemoglobin ≥ 8 g/dL;

               -  Serum creatinine ≤ 2 x upper limit of normal (ULN)

               -  Total serum bilirubin ≤ 3 x ULN;

               -  Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT)
                  ≤ 3x ULN, and ≤ 4 x ULN if liver metastases are present.

          7. 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;

          8. 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 study drug. Females of non-childbearing potential may
             be included if they are either surgically sterile or have been postmenopausal for ≥ 1
             year;

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

        Exclusion Criteria:

          1. Prior treatment with Vemurafenib;

          2. Known hypersensitivity to Metformin or any of its components;

          3. Previous progression of melanoma while on Metformin;

          4. 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;

          5. Pregnant, breast-feeding, or refusing double barrier contraception, oral
             contraceptives, or avoidance of pregnancy measures;

          6. 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 CTCAE grade 4 or higher adverse events in six patients
Time Frame:Duration of phase I portion, approximately six months
Safety Issue:
Description:In the phase I portion, six patients will be enrolled and observed for CTCAE grade 4 or higher events. If three or more grade 4 or higher adverse events are observed among the six patients, the study will be halted.

Secondary Outcome Measures

Measure:Overall Survival Follow up
Time Frame:Every 12 weeks (+/- 7 days) after last drug dose, for up to 3 full years
Safety Issue:
Description:Patients will be followed for up to three years following the last treatment administration. The Investigator or designees will make every possible attempt at least every 12 weeks (±7 days), for up to three years after the last treatment to contact the patient or family to obtain the survival information of the patient and, if applicable, the start date of additional anticancer treatment.
Measure:Number of adverse events
Time Frame:Duration of study, estimated to be approximately 60 months
Safety Issue:
Description:Descriptive statistics of all AEs observed during the study period.
Measure:type of adverse events
Time Frame:Duration of study, estimated to be approximately 60 months
Safety Issue:
Description:Descriptive statistics of all AEs observed during the study period.
Measure:Objective response rate (ORR)as measure of efficacy
Time Frame:Duration of study (approximately 60 months)
Safety Issue:
Description:Efficacy estimated as the objective response rate (ORR), which is the sum of Partial Responses (PR) and Complete Responses (CR) as determined by RECIST 1.1

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 BRAFV600E+ Melanoma

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