Clinical trial · Interventional
Carboplatin-Paclitaxel-Bevacizumab vs Carbo-Pacli-Beva-Rucaparib vs Carbo-Pacli-Ruca, Selected According to HRD Status, in Patients With Advanced Ovarian, Primary Peritoneal and Fallopian Tube Cancer, Preceded by a Phase I Dose Escalation Study on Ruca-Beva Combination
A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, 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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This trial is a randomized, open-label Phase I-2 multi-center study designed to evaluate the effect of Carboplatin-Paclitaxel-Bevacizumab (in combination and maintenance) vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib (Rucaparib only in maintenance) vs Carboplatin-Paclitaxel-Rucaparib (Rucaparib only in maintenance) on progression-free survival in patients with advanced high grade ovarian cancer treated according to HRD status . The trial will test the hypothesis that Carboplatin-Paclitaxel-Bevacizumab-Rucaparib and the Carboplatin-Paclitaxel-Rucaparib arms will improve the progression-free survival in comparison to standard Carboplatin-Paclitaxel-Bevacizumab in HRD negative (HR proficient) patients and that Carboplatin-Paclitaxel-Bevacizumab-Rucaparib will improve PFS with respect to Carboplatin-Paclitaxel-Rucaparib in HRD positive patients. The randomized phase of the study will be preceded by a single arm Phase I study which will be conducted only in the National Cancer Institute of Milan, aiming at evaluating the MTD of the combination Rucaparib-Bevacizumab. Once the MTD has been reached, the randomized study will start.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced (Stage IIIB-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer | Fallopian Tube Neoplasm | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| Carboplatin | Drug | Carboplatin | ALIAS |
| Paclitaxel | Drug | Paclitaxel | ALIAS |
| Rucaparib | Drug | Rucaparib | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- OTHER
- label
- Standard treatment
- description
- Carboplatin AUC 5 + Paclitaxel 175 mg/mq d 1 q 21 for 6 cycles + Bevacizumab 15 mg/kg d 1 q 21 days for 22 cycles (in combination and maintenance)
- interventionNames
- Drug: Carboplatin
- Drug: Paclitaxel
- Drug: Bevacizumab
- type
- EXPERIMENTAL
- label
- Carboplatin + Paclitaxel + Bevacizumab + Rucaparib
- description
- Carboplatin AUC 5 + Paclitaxel 175 mg/mq d1 q 21 days for 6 cycles + Bevacizumab 15 mg/kg d1 q 21 for 22 cycles (in combination and maintenance) + Rucaparib at the dose defined by the Phase I study continuously for 2 years (Rucaparib only in maintenance)
- interventionNames
- Drug: Carboplatin
- Drug: Paclitaxel
- Drug: Bevacizumab
- Drug: Rucaparib
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
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, 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. 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; 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. 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: 1. Curatively treated non-melanoma skin cancer; 2. Breast cancer treated curatively ≥5 years ago, or other solid tumor treated curatively ≥5 years ago, without evidence of recurrence; 3. 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.
References
Publications (64)
- BACKGROUNDDe Bono JS, Mina LA, Gonzalez M, Curtin NJ, Wang E, Henshaw JW, et al. First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors. J Clin Oncol. 2013;31(suppl):2580.
- BACKGROUNDIain A. McNeish, Amit M. Oza, Robert L. Coleman, et al. Results of ARIEL2: A Phase II trial to prospectively identify ovarian cancer patients likely to respond to rucaparib using tumor genetic analysis. J Clin Oncol 33, 2015 (suppl; abstr 5508)
- BACKGROUNDGourley, C. McCavigan, A Perren, T et al Molecular subgroup of high-grade serous ovarian cancer (HGSOC) as a predictor of outcome following bevacizumab. Abstract 5502 ASC0 2014
- RESULTSiegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29. doi: 10.3322/caac.20138. Epub 2012 Jan 4. PMID 22237781
- RESULTChan JK, Cheung MK, Husain A, Teng NN, West D, Whittemore AS, Berek JS, Osann K. Patterns and progress in ovarian cancer over 14 years. Obstet Gynecol. 2006 Sep;108(3 Pt 1):521-8. doi: 10.1097/01.AOG.0000231680.58221.a7. PMID 16946210
- RESULTEngel J, Eckel R, Schubert-Fritschle G, Kerr J, Kuhn W, Diebold J, Kimmig R, Rehbock J, Holzel D. Moderate progress for ovarian cancer in the last 20 years: prolongation of survival, but no improvement in the cure rate. Eur J Cancer. 2002 Dec;38(18):2435-45. doi: 10.1016/s0959-8049(02)00495-1. PMID 12460789
- RESULTHarries M, Gore M. Part I: chemotherapy for epithelial ovarian cancer-treatment at first diagnosis. Lancet Oncol. 2002 Sep;3(9):529-36. doi: 10.1016/s1470-2045(02)00846-x. PMID 12217790
- RESULTInternational Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. doi: 10.1016/S0140-6736(02)09738-6.