NCT02755844

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

A Phase I/II Trial to Assess the Safety and Efficacy of Metronomic Cyclophosphamide, Metformin and Olaparib in Recurrent Advanced/Metastatic Endometrial Cancer Patients

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 35 (actual)
• Sponsor: Hospices Civils de Lyon · Academic / Other
• Sex: Female
• Age: 18 Years – 81 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Recurrent Endometrial Cancer

Interventions

Type	Name	Description
DRUG	Olaparib	Olaparib tablet dose will be dose-escalated on 4 dose levels , guided by a continual reassessment method (CRM). One cycle will be 28 days (4 weeks) in duration, except for cycle 1 which will be 6 weeks.
DRUG	metformin	From week 3 metformin will be gradually escalated from 500 mg/day to 1500 mg/day with weekly 500 mg dose escalation levels
DRUG	metronomic cyclophosphamide	from week 2 Metronomic cyclophosphamide will be given continuously on an oral daily basis at 50 mg qd

Timeline

• Start date: 2016-09-23
• Primary completion: 2018-11-01
• Completion: 2020-06-01
• First posted: 2016-04-29
• Last updated: 2025-10-02

Locations

6 sites across 1 country: France