Phenformin + BRAF/MEK Inhibitors for Melanoma

Phase 1

Waitlist Available

Led By Paul Chapman, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial will test whether giving phenformin with a standard drug combination for treating melanoma is safe.

Who is the study for?

This trial is for adults with advanced melanoma that has a specific BRAF V600 mutation. Participants must be in good physical condition, have measurable cancer growth, and their major organs need to function well. They can't join if they're pregnant, on certain medications like other BRAF inhibitors or steroids beyond replacement doses, have diabetes or severe lung disease, or any other serious health issues.

What is being tested?

The study tests the safety of combining Phenformin with standard FDA-approved treatments (Trametinib and Dabrafenib) for metastatic melanoma with a BRAF mutation. It aims to see how well patients tolerate this combination and what effects it has on their cancer.

What are the potential side effects?

Potential side effects may include digestive problems, blood sugar changes due to Phenformin; skin rash, fever from Dabrafenib; and vision changes or heart issues from Trametinib. Each drug also carries its own risk profile which will be monitored throughout the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Disease-free survival

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dabrafenib, Trametinib & PhenforminExperimental Treatment3 Interventions

This is a multi-institution single-arm phase I trial with an expansion cohort at the MTD of Phenformin, in patients with metastatic BRAFV600E/K mutated melanoma. In the dose escalation phase, cohorts of patients will be treated with standard dose Dabrafenib (150 mg PO BID) plus Trametinib (2 mg PO QD) and increasing doses of Phenformin. In the dose-escalation phase of the trial, both patients who have already been treated with a BRAF and/or MEK inhibitor, and treatment-naïve patients will be eligible. The maximally tolerated Phenformin dose was determined to be 100 mg BID. The dose-expansion cohort will enroll up to 10 patients who are treatment- naïve for BRAF inhibitor. In this cohort, patients may be treated with any of the 3 FDA-approved BRAFi/MEKi combinations: dabrafenib/trametinib, vemurafenib/cobimetinib, or encorafenib/binimetinib.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trametinib

2014

Completed Phase 2

~1630

Dabrafenib

2011

Completed Phase 3

~4120