Pilot Study Evaluating the Efficacy and Safety of Metformin in Melanoma

NCT01840007 | Completed Phase 2

• 2 other identifiers: 10-PP-172010-024322-38
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Response rate

  The primary evaluation criteria is the response rate (response rate, RR) defined by the ratio between the total number of patients with a complete response (complete response, CR) or partial (partial response, PR) and the total number of patients in the study. Partial or complete responses will be defined by RECIST 1.1 (15) criteria : * Complete response: disappearance of all targets lesions * Partial response: decrease of at least 30% of the sum of the biggest diameters of each target lesion All others patients, including those for who the response couldn't be measured, will be considered non-responders.

  Once time after 6 months of treatment by metformine

Secondary Outcomes (1)

• the overall survival, the survival without progress (PFS), the tolerance, and the quality of life.

  6 times

Study Arms (1)

Metformin

EXPERIMENTAL

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.

Drug: Metformin Group

Interventions

Metformin Group DRUG

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.

Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (2)

Bahadoran

Nice, Alpes-Maritimes, 06200, France

Location

MORTIER Laurent

Lille, Nord, 59000, France

Location

Related Publications (1)

• Montaudie H, Cerezo M, Bahadoran P, Roger C, Passeron T, Machet L, Arnault JP, Verneuil L, Maubec E, Aubin F, Granel F, Giacchero D, Hofman V, Lacour JP, Maryline A, Ballotti R, Rocchi S. Metformin monotherapy in melanoma: a pilot, open-label, prospective, and multicentric study indicates no benefit. Pigment Cell Melanoma Res. 2017 May;30(3):378-380. doi: 10.1111/pcmr.12576. Epub 2017 Apr 22. No abstract available.

  PMID: 28122176 RESULT

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• BAHADORAN Philippe, PHD

  Service de Dermatologie - Hôpital de l'Archet - CHU de Nice

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: August 30, 2011
• Primary Completion: May 28, 2015
• Study Completion: November 18, 2015
• Last Updated: March 31, 2026

Record last verified: 2013-02

Locations

FR (2)