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

NCT03462212 | Unknown Phase 1

• 1 other identifier: 3329
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 7

Brief Summary

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

Advanced (Stage IIIB-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I Primary Objective: MTD

  To identify the Maximum Tolerated Dose (MTD) of the combination Rucaparib-Bevacizumab in stage IIIB-C-IV ovarian cancer patients

  4 months

• Phase II Primary Objective: PFS

  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 according to Homologous Recombination Deficient (HRD) status.

  from the date of randomization to the date of documented progression disease, recurrence or death (whichever occurs first), assessed up to 64 months

Secondary Outcomes (17)

• Phase I Secondary Objectives: toxicity of the Rucaparib-Bevacizumab combination in terms of haematologic and non haematologic events

  4 months

• Phase I Secondary Objectives: maximum plasma concentration (Cmax at Steady State) of Rucaparib

  will be evaluated during cycle 1, on days -7,1,21

• Phase I Secondary Objectives: minimal plasma concentration (Cmin at Steady State) of Rucaparib

  will be evaluated during cycle 1, on days -7,1,21

• Phase I Secondary Objectives: Area Under Curve (AUC)

  will be evaluated during cycle 1, on days -7,1,21

• Phase I Secondary Objectives: Cmax

  will be evaluated during cycle 1, on day1

Study Arms (3)

Standard treatment

OTHER

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)

Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab

Carboplatin + Paclitaxel + Bevacizumab + Rucaparib

EXPERIMENTAL

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)

Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab; Drug: Rucaparib

Carboplatin + Paclitaxel + Rucaparib

EXPERIMENTAL

Carboplatin AUC 5 + Paclitaxel 175 mg/mq d1 q 21 days for 6 cycles + Rucaparib 600 mg BID continuously for 2 years (Rucaparib only as maintenance).

Drug: Carboplatin; Drug: Paclitaxel; Drug: Rucaparib

Interventions

Carboplatin DRUG

chemotherapy medication

Carboplatin + Paclitaxel + Bevacizumab + Rucaparib; Carboplatin + Paclitaxel + Rucaparib; Standard treatment

Paclitaxel DRUG

chemotherapy medication

Carboplatin + Paclitaxel + Bevacizumab + Rucaparib; Carboplatin + Paclitaxel + Rucaparib; Standard treatment

Bevacizumab DRUG

Angiogenesis inhibitor

Carboplatin + Paclitaxel + Bevacizumab + Rucaparib; Standard treatment

Rucaparib DRUG

PARP inhibitor

Carboplatin + Paclitaxel + Bevacizumab + Rucaparib; Carboplatin + Paclitaxel + Rucaparib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Archival tumor tissue available. At progression fresh biopsy is optional for patients willing to submit ;
• ECOG Performance Status of 0-1;
• Measurable and not measurable disease;
• 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);
• 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;
• Able to understand and give written informed consent;
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

You may not qualify if:

• Women who are pregnant or lactating;
• Presence of brain or other central nervous system metastases, not adequately controlled by treatment;
• Prior Anticancer treatment;
• Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 3 weeks prior to randomization;
• 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);
• Known active HIV, hepatitis B or C infection;
• Concurrent treatment with immunosuppressive or investigational agents;
• 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);
• 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);

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator
• Foundation Medicine: collaborator

Study Sites (7)

Ospedale Mater Salutis

Legnago, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, Italy

RECRUITING

Azienda Ospedaliera di Perugia

Perugia, Italy

RECRUITING

Nuovo Ospedale degli Infermi

Ponderano, Italy

RECRUITING

Fondazione Policlinico Universitario A.Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS

Turin, Italy

RECRUITING

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• Lorusso D, Maltese G, Sabatucci I, Cresta S, Matteo C, Ceruti T, D'Incalci M, Zucchetti M, Raspagliesi F, Sonetto C, Sinno V, Ronzulli D, Giolitto S, de Braud F. Phase I Study of Rucaparib in Combination with Bevacizumab in Ovarian Cancer Patients: Maximum Tolerated Dose and Pharmacokinetic Profile. Target Oncol. 2021 Jan;16(1):59-68. doi: 10.1007/s11523-020-00780-4. Epub 2020 Dec 28.

  PMID: 33369704 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms

Interventions

Carboplatin; Paclitaxel; Bevacizumab; rucaparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Domenica Lorusso, Prof.

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Domenica Lorusso, Prof.

CONTACT

0630158545; domenica.lorusso@policlinicogemelli.it

Serena Giolitto, MSc

CONTACT

0630158545; serena.giolitto@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 12, 2018
• Study Start: March 17, 2021
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: August 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)