Patients with high grade serous or high grade endometrioid or other high grade epithelial non mucinous ovarian tumor, with at least one previous line of platinum-taxane chemotherapy, and present with platinum resistant disease (PRR) or platinum-sensitive relapse (PSR), whatever the line of chemotherapy given at relapse. MedDRA version: 20.0 Level: LLT Classification code 10033130 Term: Ovarian cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Olaparib
Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Tablet
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusio
Sponsors
ARCAGY-GINCO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with platinum resistant relapse I-1 Female Patient must be =18 years of age. I-2 Signed informed consent and ability to comply with treatment and follow-up. I-3 Patient with : Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer, histologically confirmed (based on local histopathological findings): high grade serous or high grade endometrioid or other high grade epithelial non mucinous ovarian tumor. I-4 Patient who has completed at least one line of platinum-taxane chemotherapy, and presents with platinum resistant relapse (resistant disease defined by a tumor progression less than six months after the last dose of platinum) [Note: the patient may have received one or even more line of platinum based chemotherapy]. I-5 Patient who didn’t receive any of the tested drugs, or previously received either bevacizumab or olaparib BUT NOT the combination of both drugs. I-6 At least one measurable or evaluable lesion that can be accurately assessed at baseline by computed tomography (CT) (or magnetic resonance imaging [MRI] where CT is contraindicated) and is suitable for repeated assessment as per irRC. The baseline scan must be obtained within 28 days of first dose. I-7 Availability of a pre-treatment tumor sample (archival FFPE block or fresh biopsy if feasible) lasting of less than 3 month before inclusion into the study and performed AFTER the last chemotherapy administration. I-8 Patient not amenable to cytoreductive surgery at the time of relapse (surgery is not allowed during the protocole treatment). I-9 Patient must have normal organ and bone marrow function I-10 Expectancy of at least 12 weeks I-11 Eastern Cooperative Oncology Group (ECOG) performance status 0-1. I-12 Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment (see protocol appendix 1). I-13 As this study will include patients in France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social category. Patients with platinum sensitive relapse I-1 Female Patient must be =18 years of age. I-2 Signed informed consent and ability to comply with treatment and follow-up. I-3 Patient with : Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer, histologically confirmed (based on local histopathological findings): high grade serous or high grade endometrioid or other high grade epithelial non mucinous ovarian tumor. I-4 Patient who is in platinum-sensitive relapse, whatever the line of chemotherapy given at relapse [Note: any chemotherapy previously administered must have contained a platinum compound]. The platinum sensitive relapse is defined by a tumor progression occurring more than six months after the last dose of platinum chemotherapy. I-5 Patient who didn’t receive any of the tested drugs, or previously received either bevacizumab or olaparib BUT NOT the combination of both drugs. I-6 At least one measurable or evaluable lesion that can be accurately assessed at baseline by computed tomography (CT) (or magnetic resonance imaging [MRI] where CT is contraindicated) and is suitable for repeated assessment as per irRC. The baseline scan must be obtained within 28 days of first dose. I-7 Availability of a pre-treatment tumor sample (archival FFPE block or fresh biopsy if feasible) lasting of less than 3 month before inclusion into the study and performed AFTER the last chemotherapy administ
Exclusion criteria
Exclusion criteria: E-1 Non-epithelial origin of the tumor (i.e. germ cell tumor). E-2 Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma. E-3 Carcinosarcoma (Mixed Mullerian Tumor) E-4 Patient with synchronous primary endometrial cancer unless both of the following criteria are met: • Stage 325 mg/day. E-18 Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. The required washout period prior to starting study treatment is 2 weeks. E-19 Concomitant use of known strong E-20 Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy. E-21 Clinically significant (e.g. active) cardiovascular disease, Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to inclusion. E-22 History Clinically significant (e.g. active) cardiovascular disease, E-23 Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation). E-24 History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to inclusion) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to incl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is the rate of clinical and radiological non-progressive disease, as assessed by immune-related response criteria (irRC) (Wolchok et al. 2009) : •At 3 months in the PRR cohort •At 6 months in the PSR cohort ;Secondary Objective: •CA 125 decline as expressed by the KELIM parameter •Progression free survival (PFS) •Overall survival (OS) •Tumor response •Toxicity as assessed by CTCAE V.5.0 scale ;Primary end point(s): The primary endpoint will be progression free survival based on investigators’ review of objective radiological findings as per the immune-related response criteria.;Timepoint(s) of evaluation of this end point: The rate of non-progressive disease (at 3 months in the PRR cohort and at 6 months in the PSR cohort) will be estimated using the Kaplan-Meier method. Confidence intervals will be provided at the 90% 2-sided confidence level. The lower limit of the 90% bilateral confidence interval being equivalent to the lower limit of the 95% unilateral confidence interval. The study conducted in the PRR cohort will be declared positive for the primary endpoint if the lower boundary of the 90% 2-sided confidence interval is higher than 50%. The study conducted in the PSR cohort will be declared positive for the primary endpoint if the lower boundary of the 90% 2-sided confidence interval is higher than 65%. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CA 125 decline Progression free survival Overall survival Tumor response Toxicity ;Timepoint(s) of evaluation of this end point: The CA 125 decline wil be calculated between inclusion and end of follow-up (at 3 months in the PRR cohort, at 6 months in the PSR cohort). Summarize by mean (SD) or median (25 and 75 percentils) depending if the data distribution is normal or not. The PFS wil be calculated between the date of inclusion and the date of progression or death. The time to death wil be calculated between the date of inclusion and the date of death. The tumour response will be described using the overall response categories, i.e., CR, PR, SD, NE, PD, NED. The toxicity will be described by the frequency and percentages of patients who had at least one AE | — |
Countries
France
Contacts
Public ContactMichèle TORRES-MACQUE
ARCAGY-GINECO
Outcome results
None listed