Phenformin + BRAF/MEK Inhibitors for Melanoma

Recruiting at 2 trial locations

Overseen By Michael A. Postow

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Hypoglycemics, Vemurafenib, Encorafenib, Dabrafenib

Disqualifiers: Diabetes, Renal failure, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test whether it is safe to give phenformin with the standard drug combination of one of 3 FDA-approved combinations of BRAF inhibitor + MEK inhibitor which are standard treatments for patients with metastatic melanoma whose melanoma has a mutation in a gene called BRAF.

Research Team

Michael Postow, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Inclusion Criteria

My melanoma is at an advanced stage and cannot be removed by surgery.

I can swallow pills and follow treatment instructions.

My melanoma diagnosis has been confirmed by my treatment center.

Exclusion Criteria

I have liver or kidney disease.

I have a known G6PD deficiency.

Your heart's electrical activity (QTc interval) is longer than 500 milliseconds, unless you have a specific heart condition called bundle branch block.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Cohorts of patients are treated with standard dose Dabrafenib plus Trametinib and increasing doses of Phenformin to determine the maximally tolerated dose.

8-12 weeks

Dose Expansion

Up to 10 treatment-naïve patients are treated with the maximally tolerated dose of Phenformin in combination with any of the 3 FDA-approved BRAFi/MEKi combinations.

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment using RECIST v1.1 criteria.

2 years

Treatment Details

Interventions

• Dabrafenib
• Phenformin
• Trametinib

Trial Overview 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.

Participant Groups

Group I: Dabrafenib, Trametinib & Phenformin Experimental Treatment 3 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.

Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation
• Adjuvant treatment of melanoma with a BRAF V600 mutation

Approved in United States as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600E mutation
• Adjuvant treatment of melanoma with a BRAF V600E or V600K mutation
• Metastatic non-small cell lung cancer with a BRAF V600E mutation

Approved in Canada as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation
• Adjuvant treatment of melanoma with a BRAF V600 mutation

Approved in Japan as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+