A randomized phase II trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib in patients with advanced (stage III B-C-IV) ovarian, primary peritoneal and Fallopian tube cancer preceded by a phase I dose escalation study on Rucaparib-Bevacizumab combination .

Phase 1

• Conditions: Advanced (stage III B-C-IV) ovarian, primary peritoneal and Fallopian tube cancer.; MedDRA version: 20.0Level: LLTClassification code 10006888Term: Ca ovarySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10061269Term: Malignant peritoneal neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002860-42-IT
• Lead Sponsor: FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-04
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 234

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 <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);
• Alkaline phosphatase < 1.5 x ULN for the institution (if > 1.5 x ULN, then alkaline phosphatase liver fraction must be < 1.5 ULN);
• Serum creatinine = 1.5 x ULN for the institution (or calculated creatinine clearance = 45 mL/min/1.73 m2);
7. 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;
8. Able to understand and give written informed consent;
9. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment;

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 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified