Critères d'inclusion : - Woman older than 18 years and younger than 81 year old
- Patients with histologically and/or cytologically documented endometrial carcinoma (type I or type II), recurrent after platinum-based chemotherapy.
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Archival tumor tissue available, or tumor lesion biopsy feasible
- There is no limitation to prior number of therapies
- Patients who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Patients with adequate bone marrow function
-> Absolute granulocyte count ≥ 1.5 x 10 9 /L
-> Platelet count ≥ 100 x 10 9 /L
-> Haemoglobin ≥ 9 g/dL
- Patients with adequate renal function :
* Calculated creatinine clearance, according to the Modification of the Diet in Renal Disease (MDRD) formula >= 60 ml/min
- Patients with adequate hepatic function
*Serum total bilirubin < 1.25 x upper normal limit (UNL) and aspartate aminotransferase (AST)/Alanine Amino transferase (ALT) ≤ 2.5 X UNL (≤ 5 X UNL for patients with liver metastases)
- Patients must have a life expectancy ≥ 16 weeks
- Female patients who are of childbearing potential: evidence of non-childbearing status, practicing a medically acceptable method of birth control during the study and 12 months after the end of treatment
- Patients who gave its written informed consent to participate to the study
- Patients affiliated to a social insurance regime
Critères de non-inclusion : - Illness, incompatible with metformin treatment, in particular those associated with a risk of hypoperfusion or hypoxia (not limited to): acute or chronic renal failure (creatinine clearance < 60 ml/min, according to the MDRD formula); lactic ketoacidosis; septic shock; congestive heart failure; respiratory distress; liver failure; chronic alcoholism; uncontrolled seizures; age > 80 years; allergy/hypersensitivity to metformin.
- Previous treatment with cyclophosphamide; or allergy/hypersensitivity to cyclophosphamide.
- Any previous treatment with a poly-adenosine diphosphate ribose (ADP) ribose polymerase (PARP) inhibitor, including olaparib.
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
- Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment. The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
- Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin boceprevir, telaprevir and nelfinavir and inducers such phenobarbital, phenytoin, carbamazepine, rifampicin.
- Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
- Treatment with other investigational agents.
- Bowel occlusive syndrome or other gastro-intestinal disorder that does not allow oral medication such as malabsorption.
- Female patients who are pregnant or lactating, Active infection to HIV, hepatitis B or C, or have other forms of hepatitis or cirrhosis.
- Symptomatic uncontrolled brain metastases. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
- Major surgery within 14 days of starting study treatment
- Patients must have recovered from any effects of any major surgery.
- Resting ECG with corrected QT interval (QTc) > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- Concomitant treatment with vitamin K antagonists
- Patients under guardianship.