Safety and Efficacy of Metronomic Cyclophosphamide, Metformin and Olaparib in Endometrial Cancer … (NCT02755844) | Clinical Trial Compass
CompletedPhase 1/2
Safety and Efficacy of Metronomic Cyclophosphamide, Metformin and Olaparib in Endometrial Cancer Patients
France35 participantsStarted 2016-09-23
Plain-language summary
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.
Who can participate
Age range
18 Years – 81 Years
Sex
FEMALE
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
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 w…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Recommended phase 2 trial (RP2D) dose of olaparib combined to metronomic cyclophosphamide and metformin
Timeframe: through the 6th week of treatment (cycle 1)