RUCAPARIB for Ovarian cancer | Primary peritoneal cancer | Fallopian tube cancer

Inclusion criteria

• {"criterion_text":"- Women aged >/= 18 years at the time of study inclusion\n- Patients with newly diagnosed, histologically confirmed, high grade serous, high grade endometrioidFIGO 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; 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;\n- Archival tumor tissue available. At progression fresh biopsy is optional for patients willing to submit\n- ECOG Performance Status of 0–1\n- 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 <2 ULN for the institution AST and/or ALT ≤ 2.5 x ULN for the institution. (or ≤ 5 x ULN if liver metastases are present); - Serum creatinine ≤ 1.5 x ULN for the institution (or calculated creatinine clearance ≥ 45 mL/min/1.73 m2);\n- Adequate bone marrow function, defined as: - Total leukocytes >/= 2.5 x 109/L; - ANC >/= 1.5 x 109/L; - Platelet count >/= 100 x 109/L;\n- Able to understand and give written informed consent\n- Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment;"}

Exclusion criteria

• {"criterion_text":"- Women who are pregnant or lactating\n- Serious active infection requiring i.v. antibiotics at enrolment;\n- Known hypersensitivity to any of the study drugs or excipients (including cremophor and hamster Ovary cell products);\n- 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;\n- Prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with absorption of study drug;\n- Received administration of strong CYP1A2 or CYP3A4 inhibitors ≤7 days prior to first dose of Rucaparib or have on-going requirements for these medications.\n- Presence of brain or other central nervous system metastases, not adequately controlled by treatment\n- Prior Anticancer treatment for ovarian cancer\n- Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 3 weeks prior to randomization\n- Another primary malignancy except for: - Curatively treated non-melanoma skin cancer; - Breast cancer treated curatively ≥5 years ago, or other solid tumor treated curatively ≥5 years ago, without evidence of recurrence; - Synchronous endometrioid endometrial cancer (except for Stage 1A G1/G2);\n- Known active HIV, hepatitis B or C infection;\n- Concurrent treatment with immunosuppressive or investigational agents\n- 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);\n- 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);"}

Primary endpoints

• {"endpoint_text":"- Phase I: Maximum Tolerated Dose (MTD): defined as the maximum dose at which no limiting toxicities occurr (see belove the definition of limiting toxicities) to recommend for the Phase II randomized design of the trial","definition_or_measurement_approach":"MTD defined as the maximum dose at which no limiting toxicities occur; used to recommend dose for Phase II randomized design (Phase I primary objective: To identify the MTD of the combination Rucaparib-Bevacizumab)."}
• {"endpoint_text":"- Phase II: Progression-free survival, defined as the time from the date of randomization to the date of documented progressive disease, recurrence or death (whichever occurs first) in patients treated according to HRD status.","definition_or_measurement_approach":"PFS measured as time from randomization to documented progressive disease, recurrence, or death (whichever occurs first) in patients treated according to HRD status."}

Secondary endpoints

• {"endpoint_text":"- Phase I: Toxicity of the Rucaparib-Bevacizumab combination in terms of haematologic and non haematologic events. Toxicity will be evaluated according to U.S. NCI Common Toxicity Criteria version 5.0","definition_or_measurement_approach":"Toxicity evaluated according to U.S. NCI CTCAE v5.0; describes haematologic and non-haematologic events."}
• {"endpoint_text":"- Phase I: Pharmacokinetic parameter in patient receiving the combination of Rucaparib and Bevacizumab","definition_or_measurement_approach":"Pharmacokinetic parameters measured in patients receiving the combination (specific PK measures not listed)."}
• {"endpoint_text":"- Phase II: Overall survival defined as the time from the date of randomization to the date of death in patients treated accordinf to HRD status","definition_or_measurement_approach":"Overall survival measured as time from randomization to death in patients treated according to HRD status."}
• {"endpoint_text":"- Phase II: Progression-free survival 2 (PFS2) defined as time from randomisation to second objective disease progression or death in patients treated accordinf to HRD status","definition_or_measurement_approach":"PFS2 measured as time from randomization to second objective disease progression or death in patients treated according to HRD status."}
• {"endpoint_text":"- Phase II: To compare the time from randomization to first subsequent therapy or death (TFST) in patients treated according to HRD status","definition_or_measurement_approach":"TFST measured as time from randomization to first subsequent therapy or death."}
• {"endpoint_text":"- Phase II: Time to second subsequent therapy (TSST) defined as time from randomisation to the initiation of second subsequent therapy or death in patients treated according to HRD status","definition_or_measurement_approach":"TSST measured as time from randomization to initiation of second subsequent therapy or death."}
• {"endpoint_text":"- Phase II: Best target lesion response, defined as best change in sum of the target lesions from baseline to disease progression or by the modifications of CA 125 according to GCIG criteria","definition_or_measurement_approach":"Best target lesion response defined as best change in sum of target lesions from baseline to progression or by CA125 modifications per GCIG criteria."}
• {"endpoint_text":"- Phase II: Adverse Events and laboratory abnormalities evaluated according to CTCAE version 5.0","definition_or_measurement_approach":"Adverse events and lab abnormalities evaluated per CTCAE v5.0."}
• {"endpoint_text":"- Phase II: Patient-reported outcome (PRO) of disease-related symptoms utilizing Functional Assessment of Cancer Therapy-Ovarian (FACT-O) and Euro-Quality of Life 5D (EQ-5D) tool","definition_or_measurement_approach":"PRO measured using FACT-O and EQ-5D instruments."}

Italy

Earliest CTIS Part Ii Submission Date

23-09-2024

Latest Decision Or Authorization Date

10-06-2025

Processing Time Days

260

Number Of Sites

19

Number Of Participants

300

Primary sponsor

Full Name

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Euromed Pharma Services S.r.l.","duties_or_roles":"Rucaparib IMP labeling procedures","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Fullcro S.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}