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About
Endometrial cancer ranks 11th in terms of incidence (7275 / year) and mortality (2025 deaths/ year). The 5-year overall survivals of patients at diagnosis with locally advanced and metastatic carcinomas are about 50% and 15% respectively. Beyond first line treatment with platinum-based chemotherapy, there is lack of effective drug in this disease, which explains the poor prognosis of patients.
The prognosis of metastatic endometrial cancer patients is poor, and few drugs have been shown to be effective beyond first chemotherapy line.
Endometrial carcinomas are characterized by frequent alterations of PI3K-AKT-mTor; IGF1R and of DNA repair pathways. Phosphatase and tensin homologue (PTEN)-phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTor) and DNA repair pathways interact, and inhibition of PI3K-AKT-mTor signaling pathway may alter DNA damage repair.
Metronomic cyclophosphamide regimen may increase the anti-proliferative effects of olaparib because it is an alkylating agent, and it exerts anti-angiogenic effects, with a favorable toxicity profile.
Metformin may increase the anti-proliferative effects of olaparib because it downregulates IGF1R and PI3K-AKT-mTor pathways, with no additive toxicity.
Enrollment
Sex
Ages
Volunteers
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
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
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.
Primary purpose
Allocation
Interventional model
Masking
35 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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