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COMPLETED
NCT02755844
PHASE1/PHASE2

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

Sponsor: Hospices Civils de Lyon

View on ClinicalTrials.gov

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.

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

Key Details

Gender

FEMALE

Age Range

18 Years - 81 Years

Study Type

INTERVENTIONAL

Enrollment

35

Start Date

2016-09-23

Completion Date

2020-06

Last Updated

2026-05-27

Healthy Volunteers

No

Interventions

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

Locations (6)

Service d'Oncologie Médicale, Centre François Baclesse

Caen, France

Département de Cancérologie Cervico-Faciale et Thoracique, Centre Oscar Lambret

Lille, France

Département d'Oncologie Médicale, Centre Antoine Lacassagne

Nice, France

Service d'Oncologie Médicale, Institut Curie

Paris, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Comité Gynécologique, Institut Gustave Roussy

Villejuif, France