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.

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.

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.

• Overall survival (OS) is defined by the duration (number of days) between the start of treatment (J1) and the date of death from anything.
• Progression-free survival (PFS) is defined by the duration (number of days) between the start of treatment (J1) and the observation of a progression or death. Tumor progression is defined by an increase of at least 20% of the sum of the biggest diameters of each target lesion.
• The duration of the response is determined by the time (in days) between the date (visit) which is recorded a response to the treatment (complete or partial) and the date (visit) which is recorded an increase or the date of death.
• To evaluate the quality of life, a questionnaire EORTC QLQ-C30 version 3 (16), validated in French, will be completed by the patient at visits V1 (J1), V3 (M2), V5 (M4) and V7 (M6) (Annex X).