Combining Vemurafenib and Metformin for Melanoma Treatment

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

This study is testing if combining the cancer drug Vemurafenib with Metformin can help people with advanced melanoma feel better and live longer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Louisville (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Louisville, Kentucky)
• Trial ID: NCT01638676 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of Vemurafenib, an FDA-approved medication, in combination with Metformin for patients with unresectable Stage IIIC and Stage IV BRAFV600E+ melanoma. The study consists of two phases: Phase I focuses on assessing the safety of the drug combination, while Phase II examines its clinical activity in improving patient outcomes. Participants will receive the treatment in 28-day cycles until disease progression or unacceptable toxicity occurs. The study aims to determine if this combination can enhance response rates and survival in metastatic melanoma patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed BRAFV600E melanoma at Stage IIIC or IV.

Not a fit: Patients with melanoma that is resectable or those without the BRAFV600E mutation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and response to therapy in patients with advanced melanoma.

How similar studies have performed: Previous studies have shown promising results with similar drug combinations in melanoma treatment, suggesting potential for success.

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

Where this trial is running

Louisville, Kentucky

• James Graham Brown Cancer Center-University of Louisville — Louisville, Kentucky, United States (Recruiting)

Study contacts

• Principal investigator: Jason A Chesney, MD PhD — James Graham Brown Cancer Center-U of Louisville

Conditions Melanoma; Unresectable melanoma; Stage IIIC and Stage IV BRAFV600E+ Melanoma