Pilot Study Evaluating the Efficacy and Safety of Metformin in Melanoma

Centre Hospitalier Universitaire de Nice

Status and phase: Completed; Phase 2

Conditions: Metastatic Melanoma (Stage IIIC Non-résécable or no Surgically Curable or Stage IV With Classification AJCC)

Treatments: Drug: Metformin Group

Study type: Interventional

Funder types: Other

Identifiers

NCT01840007

10-PP-17

2010-024322-38 (EudraCT Number)

Details and patient eligibility

About

In western countries, melanoma represents a major mistake of public health by its frequency, lethality and the increasing of incidence. Surgery can cure melanoma diagnosed very early. In other cases, it exists a risk of recurrence of lymph node and visceral. At the stage of visceral metastases, the prognosis of melanoma is catastrophic, with a median survival of 6 months. Indeed, the reference chemotherapy by dacarbazine induces a very limited response rate of 10-20%, the ipilimumab which has been authorized in the second intention, has a response rate of 10%, and other available treatments don't have a superior efficiency. Metformin is an oral antidiabetic of biguanides family which acts by inducing the activation of AMPK, a molecule which is inactivated in many cancers including the melanoma. In agreement with these data, several preclinical studies suggested that metformin has antineoplastic activity. In the case of melanoma, a study published recently has showed that metformin inhibits proliferation of melanoma cells in vitro and we confirmed for our part these results in our laboratory (INSERM U895).

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Major patients with metastatic melanoma (stage IIIC non-résécable or no surgically curable or stage IV with classification AJCC) in progression after a first-line of treatment by vemurafenib or chemotherapy, and non-eligible or non-responders to ipilimumab.

Metastases measurable by RECIST criteria. Hematologic, renal and hepatic appropriate functions. Negative pregnancy test.

Exclusion criteria

• Patients with symptomatic brain metastases and Performans Status (PS)>2. Patients with carcinomatous meningitis. Pregnant or breathfeeding women. Patients with a contraindication to the metformine. HIV infection, active infection with HBV or HCV. Patients already treated with metformin in the context of diabetes.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Metformin

Experimental group

Description:

The chosen posology is 2540 mg/day of metformin-base so 3 tablets/day of Glucophage ® 1000. Patients should take 3 tablets/day at the rate of 1tablet in morning, noon and evening to favor the absorbtion and reduce the risk of gastrointestinal intolerance. In case of missed dose, patients will be allowed to take 2 tablets on the next grip. The drug will be presented in its officinale form of Glucophage ® 1000 with specifications indicated in the Vidal dictionary. It will be provided each month, to patient, 3 boxes of 30 tablets of Glucophage ® 1000. The patient will be asked to rate each day, on a calendar, the number of tablets of Glucophage ® 1000 effectively taken. It will also ask to the patient to bring back used boxes of Glucophage ® 1000 to count any tablets not taken.

Treatment:

Drug: Metformin Group