None listed
Conditions
Interventions
Trade Name: LYNPARZA
Pharmaceutical Form: Capsule
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: range
C
Sponsors
Hospices Civils de Lyon
Eligibility
Sex/Gender
All
Inclusion criteria
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 = 2 - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
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 80 years; allergy/hypersensitivity to metformin. - Previous treatment with cyclophosphamide; or allergy/hypersensitivity to cyclophosphamide. - Any previous treatment with a 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.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 1/Non progression rate at 10 weeks - 2/Rate of best response (RECIST v.1.1) during the whole treatment period - 3/Safety throughout the study ;Timepoint(s) of evaluation of this end point: - 1/ at 10 weeks - 2/ during the whole treatment period - 3/ throughout the study | — |
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety including nature, number and grade of adverse events according to NCI-CTAE v.4 criteria in order to determine the phase 2 trial recommended dose (RP2D). RP2D is defined as the highest dose level at which less than 20% of patients experienced dose limiting toxicities during the first 6 week treatment. ;Main Objective: To assess the safety and recommended phase 2 trial dose (RP2D) of olaparib combined to metronomic cyclophosphamide and metformin in patients with recurrent advanced/metastatic endometrial carcinomas;Secondary Objective: - To assess the efficacy of olaparib combined to metronomic cyclophosphamide and metformin in patients with advanced/metastatic endometrial carcinomas; - To assess the safety of the combination throughout the study; - To obtain data on the respective pharmacodynamic effects of the 3 drugs on involved signaling pathways (PI3K-AKT-mTor-S6K; PARP1 and IGF1R in PBMCs, tumor samples and in baseline blood samples) along with potential pharmacodynamic interactions; - To obtain data on the kinetics of circulating pharmacodynamic biomarkers, including CA-125, IGF-1, insulin and circulating tumor DNA, to be related with treatments effects; - To obtain data about impact of DNA damage repair system alterations on treatment effects: homologous recombination, Lynch syndrome and other DNA repair genes. ;Timepoint(s) of evaluation of this end point: the first 6 week treatment | — |
Countries
France
Contacts
Public ContactProject manager
Hospices Civils de Lyon
Outcome results
None listed