Advanced (stage III B-C-IV) ovarian, primary peritoneal and Fallopian tube cancer. MedDRA version: 20.0 Level: LLT Classification code 10006888 Term: Ca ovary System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10016180 Term: Fallopian tube cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 1
Conditions
Interventions
Trade Name: Rubraca
Product Name: Rucaparib
Product Code: [CO-338]
Pharmaceutical Form: Tablet
INN or Proposed INN: Rucaparib Camsylate
CAS Number: 283173-50-2
Current Sponsor code: CO-338
Concentrati
Sponsors
FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Women aged = 18 years at the time of study inclusion; 2. Patients with newly diagnosed, histologically confirmed, high grade serous, high grade endometrioid, clear cell FIGO stage IIIB-C-IV epithelial ovarian cancer, primary peritoneal cancer and / or Fallopian-tube cancer. Patients with mixed histology (carcinosarcoma) are eligible providing that high grade tumor represent more than 50% of the total histology; other histotypes may be enrolled providing BRCA mutation is present. Stage III patients should have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery; 3. Archival tumor tissue available. At progression fresh biopsy is optional for patients willing to submit ; 4. ECOG Performance Status of 0–1; Protocol Version 1.0_18.07.2017 50 5. Measurable and not measurable disease; 6. Adequate renal and hepatic function, defined as: • Total serum bilirubin = 1.5 institutional ULN unless patient has Gilbert’s syndrome in which case total serum bilirubin must be 1.5 x ULN, then alkaline phosphatase liver fraction must be =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Women who are pregnant or lactating; 2.Presence of brain or other central nervous system metastases, not adequately controlled by treatment; 3. Prior Anticancer treatment; 4. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 3 weeks prior to randomization; 5. Another primary malignancy except for: a) Curatively treated non-melanoma skin cancer; b) Breast cancer treated curatively =5 years ago, or other solid tumor treated curatively =5 years ago, without evidence of recurrence; c) Synchronous endometrioid endometrial cancer (except for Stage 1A G1/G2); 6. Known active HIV, hepatitis B or C infection; 7. Concurrent treatment with immunosuppressive or investigational agents; 8. History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or subarachnoid haemorrhage within _6 months prior to the first study treatment); 9. Clinically significant (i.e. active) cardiovascular disease, including: - Myocardial infarction or unstable angina within _6 months prior to the first study treatment; - New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF); - Serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia); - Peripheral vascular disease > grade 3 (i.e.symptomatic and interfering with activities of daily living requiring repair or revision); 10. Serious active infection requiring i.v. antibiotics at enrolment; 11. Known hypersensitivity to any of the study drugs or excipients (including cremophor and hamster Ovary cell products); 12. Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer, etc.), physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications; 13. Prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with absorption of study drug; 14. Received administration of strong CYP1A2 or CYP3A4 inhibitors = 7 days prior to first dose of Rucaparib or have on going requirements for these medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I Primary Objective: -To identify the Maximum Tolerated Dose (MTD) of the combination Rucaparib-Bevacizumab in stage IIIB-C-IV ovarian cancer patients. Phase II Primary Objective: -To compare progression-free survival (PFS) of patients with advanced ovarian, primary peritoneal and Fallopian tube cancer when treated with Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs carboplatin-Paclitaxel-Rucaparib. ;Secondary Objective: Phase I Secondary Objectives: -To describe the toxicity of the Ruca-Beva combination in terms of haematologic and non haematologic events -To evaluate pharmacokinetic parameter in patients receiving the combination of Ruca and Beva. Phase II Secondary Objectives: -To compare the OS of patients receiving one of the three treatments; -To compare the PFS2 of patients receiving one of the three treatments; -To compare the time from randomisation to first subsequent therapy or death (TFST) of patients receiving one of the three treatments; -To compare the time to second subsequent therapy (TSST) of patients relatively to the three treatment arms; -To compare the ORR, according to RECIST 1.1 and/or GCIG criteria, of patients receiving one of the three treatments; -To assess the safety and tolerability of the drugs in this population; To evaluate homologous recombination deficiency (HRD) signature and its correlation with efficacy end-points; -Quality of Life ;Primary end point(s): Phase I Primary End-Point: Maximum Tolerated Dose (MTD) of the combination Rucaparib-Bevacizumab Phase II Primary Endpoint: Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Timepoint of evaluation of the Phase I Primary endpoint: Time to MTD identification Timepoint of evaluation of the Phase II Primary endpoint: The PFS defined as the time from the date of randomization to the date of documented progressive disease, recurrence or death (whichever occurs first) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoint Phase I: Toxicity of the Rucaparib-Bevacizumab combination in terms of haematologic and non haematologic events.; Secondary Endpoint Phase I: Pharmacokinetic parameter in patient receiving the combination of Rucaparib and Bevacizumab; Secondary Endpoint Phase II: Overall survival (OS); Secondary Endpoint Phase II: Progression-free survival 2 (PFS2); Secondary Endpoint Phase II: Time to first subsequent therapy (TFST); Secondary Endpoint Phase II: Time to second subsequent therapy (TSST); Secondary Endpoint Phase II: Overall response rate (ORR): CR + PR; Secondary Endpoint Phase II: Safety and tolerability; Secondary Endpoint Phase II: Patient-reported outcome (PRO) of disease-related symptoms;Timepoint(s) of evaluation of this end point: Toxicity will be observed during the first two maintenance cycles with Rucaparib; The PK will be evaluated during cycle 1 on days -7, 1 and 21; The OS will be measured from the date of randomization to the date of death; The PFS2 will be measured from randomisation to second objective disease progression or death; The TFST will be measured from randomisation to the initiation of first subsequent therapy or death.; The TSST will be measured from randomisation to the initiation of second subsequent therapy or death.; The ORR will be measured for the duration of the study; Duration of the study; Duration of the study | — |
Countries
Italy
Contacts
Public ContactDirezione Scientifica IRCCS Policli
Direzione Scientifica IRCCS Policlinico A. Gemelli
Outcome results
None listed