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

Phase 1/Phase 2
18 Years
Open (Enrolling)

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Trial Information

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

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.

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Observation of CTCAE grade 4 or higher adverse events in six patients

Outcome 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.

Outcome Time Frame:

Duration of phase I portion, approximately six months

Safety Issue:


Principal Investigator

Jason A Chesney, MD PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

James Graham Brown Cancer Center-U of Louisville


United States: Institutional Review Board

Study ID:




Start Date:

July 2012

Completion Date:

June 2019

Related Keywords:

  • Melanoma
  • Unresectable melanoma
  • Stage IIIC and Stage IV BRAFV600E+ Melanoma
  • Melanoma



James Graham Brown Cancer Center-University of Louisville Louisville, Kentucky  40202