Patients with advanced FIGO stage IIIB – IV high grade epithelial ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment MedDRA version: 20.1 Level: PT Classification code 10070908 Term: Ovarian cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: PT
Conditions
Interventions
Product Name: olaparib
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
ARCAGY Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I-1. Female Patients must be =18 years of age. I-2. Signed informed consent and ability to comply with treatment and follow-up. I-3. Patient with newly diagnosed I-3-1 Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer, I-3-2 Histologically confirmed (based on local histopathological findings): • high grade serous (see appendix 2) or • high grade endometrioid (see appendix 2) or • other epithelial non mucinous ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation I-3-3 at an advanced stage: FIGO stage IIIB, IIIC, or IV of the 1988 FIGO classification (see appendix 1). I-4. Patients who have completed prior to randomization first line platinum-taxane chemotherapy: a. Platinum-taxane based regimen must have consisted of a minimum of 6 treatment cycles and a maximum of 9. However if platinum based therapy must be discontinued early as a result of non hematological toxicity specifically related to the platinum regimen (i.e. neurotoxicity, hypersensitivity etc.), patients must have received a minimum of 4 cycles of the platinum regimen. b. Intravenous, intraperitoneal, or neoadjuvant platinum based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle. Interval debulking is allowed. I-5. Patients must have received prior to randomization a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to realize only 2 cycles of bevacizumab in combination with the last 3 cycles of platinium-based chemotherapy. Bevacizumab treatment should be planned for maintenance phase. I-6. Patients must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) from their first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout their first line treatment and prior to study randomization. I-7. Patients must be randomized at least 3 weeks and no more than 9 weeks after their last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from the previous chemotherapy must have resolved to CTC AE grade 1 or better (except alopecia and peripherical neuropathy). I-8. Patients must have normal organ and bone marrow function: a. Haemoglobin = 10.0 g/dL, with no red blood cells transfusion in the past 28 days b. Absolute neutrophil count (ANC) = 1.5 x 109/L. c. Platelet count = 100 x 109/L. d. Total bilirubin = 1.5 x institutional upper limit of normal (ULN). e. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x ULN, unless liver metastases are present in which case they must be = 5 x ULN. f. Serum creatinine = 1.25 x institutional ULN, g. Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) =1.5 and an Activated ProThrombin Time (aPTT) =1.5 x ULN. The use of full-dose oral or par
Exclusion criteria
Exclusion criteria: -Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors). -Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma. -Patients with synchronous primary endometrial cancer unless both of the following criteria are met: -stage 2 weeks in the chemotherapy course administration due to prolonged hematological recovery. -Patients receiving radiotherapy within 6 weeks prior to study treatment. -Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. -Previous allogenic bone marrow transplant. -Any previous treatment with PARP inhibitor, including olaparib. -Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period -Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day. -Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. -Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy. -Clinically significant cardiovascular disease, including: -Myocardial infarction or unstable angina within = 6 months of randomization, -NYH = grade 2 congestive heart failure (CHF), -Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG, -Peripheral vascular disease grade = 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision). -Previous Cerebro-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization. -History or evidence of hemorrhagic disorders within 6 months prior to randomization. -Evidence of bleeding diathesis or significant coagulopathy -History or clinical suspicion of brain metastases or spinal cord compression.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy by progression free survival (PFS1) investigator based according to modified Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) of olaparib maintenance compared to placebo in high grade epithelial ovarian, fallopian tube, or peritoneal cancer that are in clinical complete response or partial response following first line platinum-taxane based chemotherapy plus bevacizumab, and planned to receive bevacizumab in the maintenance phase.; Secondary Objective: 1. To determine : • time to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death • time from randomization to first subsequent therapy or death (TFST) • time from randomization to second progression (PFS2) • time from randomization to second subsequent therapy or death (TSST) • overall survival (OS) 2. To assess the safety and tolerability of olaparib maintenance compared to placebo. 3. To compare the effects of olaparib maintenance compared to placebo on Health-related Quality of Life (HRQoL) and patient reported outcomes (PROs), with consideration of patient preference. 4. To evaluate the impact of treatment and disease on resource use. ; Primary end point(s): PFS1 is defined as the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST version 1.1 or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized study treatment or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. However, if the patient progresses or dies after two or more missed visits, the p | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS) Overall survival is defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. Time to earliest progression by RECIST or CA-125 Time to earliest progression by RECIST v. 1.1 or CA-125 or death is defined as the time from randomization to the earliest date of RECIST or CA-125 progression or death by any cause. Progression according to CA-125 will be assessed according to GCIG (see appendix 8). Patients without a CA-125 progression or a RECIST progression who are still alive at the time of analysis will be censored at their last evaluable RECIST assessment or their last available CA-125 measurement, whichever is the most recent at the time of the analysis. If a patient progresses or dies after two or more missed RECIST and CA-125 assessments, then the patient will be censored at the time of their last evaluable assessment. If only one assessment is missing during this period, no censoring is required. Second Progression Free Survival (PFS2) Time from randomization to second progression is defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the primary variable PFS, or date of death. The date of second progression will be recorded by the investigator and defined according to local standard clinical practice and may involve any of; objective radiological, CA-125 or symptomatic progression or death. Second progression status will be reviewed regularly following the progression event used for the primary variable PFS (PFS1) and recorded. Patients alive and for whom a second disease progression has not been observed should be censored at the last time known to be alive | — |
Countries
Austria, Belgium, Denmark, Finland, France, Germany, Italy, Japan, Monaco, Spain, Sweden
Contacts
Public ContactProject Manager, Sylvie MIJONNET
ARCAGY-RESEARCH
Outcome results
None listed