Safety and Efficacy of Metronomic Cyclophosphamide, Metformin and Olaparib in Endometrial Cancer Patients

Inclusion Criteria: * 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 0-1 * 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 neutrophile 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, using the MDRD formula, according to the standardized IDMS method (http://www.sfndt.org/sn/eservice/calcul/eDFG.htm by ticking IDMS standardized measurement).\>= 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 practicing two medically acceptable methods of birth control since consent signature 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 Exclusion Criteria: * 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, using the MDRD formula according to the standardized IDMS method); 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 or one of its excipients or one of its metabolits. * Illness incompatible with cyclophosphamide treatment: pre-existing hemorrhagic cystitis and urinary tract obstruction * 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. A diabetic patient may be included in the study. In that case: \- If the patient is treated with metformin: Keep metformin at the usual dosage. There will be no prescription or dispensation in the study. \- If the patient is being treated with another medicine (ex Stagid): Take the advice of a diabetologist or the referring physician for the patient's diabetes for the continuation of the same treatment and the addition of metformin to 500 mg/day.