A Study of Bevacizumab (Avastin) in Neoadjuvant Therapy in Participants With International Federation of Gynecology and Obstetrics (FIGO) Stage IIIC/IV Ovarian, Tubal, or Peritoneal Cancer, Initially Unresectable

NCT ID: NCT01739218

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-01
• Study Completion Date: 2016-08-17

Brief Summary

This randomized, open-label study will evaluate the efficacy and safety of neoadjuvant bevacizumab in participants with initially unresectable, FIGO stage IIIC/IV ovarian, tubal, or peritoneal cancer. Participants will be randomized to receive 8 cycles of carboplatin plus paclitaxel with or without bevacizumab before surgery (interval debulking surgery [IDS]). Surgery will be scheduled 28 days after the last course of neoadjuvant treatment in participants with resectable cancer. Participants with unresectable cancer will go through the follow-up period. All participants will receive bevacizumab for Cycles 6 to 26.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin + Paclitaxel + Bevacizumab

Participants will receive 4 cycles of neoadjuvant therapy prior to IDS and 22 cycles of adjuvant therapy before entering long-term follow-up. Each cycle will be 3 weeks in length. Carboplatin and paclitaxel will be administered during Cycles 1 to 8. Bevacizumab will be administered during both the neoadjuvant and the adjuvant treatment periods in Cycles 1 to 26 (no treatment in Cycles 4 and 5).

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin will be administered at a dose calculated according to the Calvert formula (\[participant's glomerular filtration rate + 25\] multiplied by the target area under the concentration-time curve \[AUC\] of 5 milligrams per milliliter per minute \[mg/mL/min\]), as intravenous \[IV\] infusion over 30-60 minutes \[min\] every 3 weeks).

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered at a dose of 175 milligrams per meter-squared \[mg/m\^2\] as IV infusion over 3 hours using a rate controlling device every 3 weeks, or at a dose of 80 mg/m\^2 as IV infusion over 1 hour using a rate controlling device every week (only during Cycles 5 to 8).

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered at a dose of 15 milligrams per kilogram \[mg/kg\] as IV infusion over 30-90 min every 3 weeks.

Carboplatin + Paclitaxel

Participants will receive 4 cycles of neoadjuvant therapy prior to IDS and 22 cycles of adjuvant therapy before entering long-term follow-up. Each cycle will be 3 weeks in length. Carboplatin and paclitaxel will be administered during Cycles 1 to 8. Bevacizumab will be administered only during the adjuvant treatment period in Cycles 6 to 26.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin will be administered at a dose calculated according to the Calvert formula (\[participant's glomerular filtration rate + 25\] multiplied by the target area under the concentration-time curve \[AUC\] of 5 milligrams per milliliter per minute \[mg/mL/min\]), as intravenous \[IV\] infusion over 30-60 minutes \[min\] every 3 weeks).

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered at a dose of 175 milligrams per meter-squared \[mg/m\^2\] as IV infusion over 3 hours using a rate controlling device every 3 weeks, or at a dose of 80 mg/m\^2 as IV infusion over 1 hour using a rate controlling device every week (only during Cycles 5 to 8).

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered at a dose of 15 milligrams per kilogram \[mg/kg\] as IV infusion over 30-90 min every 3 weeks.

Interventions

Carboplatin

Carboplatin will be administered at a dose calculated according to the Calvert formula (\[participant's glomerular filtration rate + 25\] multiplied by the target area under the concentration-time curve \[AUC\] of 5 milligrams per milliliter per minute \[mg/mL/min\]), as intravenous \[IV\] infusion over 30-60 minutes \[min\] every 3 weeks).

Intervention Type: DRUG

Paclitaxel

Paclitaxel will be administered at a dose of 175 milligrams per meter-squared \[mg/m\^2\] as IV infusion over 3 hours using a rate controlling device every 3 weeks, or at a dose of 80 mg/m\^2 as IV infusion over 1 hour using a rate controlling device every week (only during Cycles 5 to 8).

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be administered at a dose of 15 milligrams per kilogram \[mg/kg\] as IV infusion over 30-90 min every 3 weeks.

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed and documented high-risk FIGO stage IIIC/IV epithelial ovarian carcinoma, fallopian tube carcinoma, or primary peritoneal carcinoma
• Not eligible for primary complete debulking surgery during a laparoscopic procedure as judged by a surgeon experienced in management of ovarian cancer
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Life expectancy greater than or equal to (>/=) 3 months
• Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards
• Beneficiaries of healthcare coverage under the social security system

Exclusion Criteria

• Non-epithelial ovarian cancer, ovarian tumor with low malignant potential, mucinous and clear cell ovarian cancer, or carcinosarcoma
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
• Previous systemic therapy for ovarian cancer
• Previous exposure to mouse CA-125 antibody
• Current or recent (within 28 days prior to Day 1 of Cycle 1) treatment with another investigational drug or previous participation in this study
• Current or recent (within 10 days prior to first study drug dose) chronic daily treatment with aspirin greater than (>) 325 milligrams (mg) per day
• Planned intraperitoneal cytotoxic chemotherapy
• Inadequate bone marrow, liver, or renal function
• History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to Day 1 of Cycle 1
• Uncontrolled hypertension
• Clinically significant (active) cardiovascular disease such as New York Heart Association (NYHA) Class II or greater congestive heart failure, or aortic aneurism
• Pre-existing peripheral neuropathy that is Common Toxicity Criteria (CTC) Grade >/=2
• Known hypersensitivity to bevacizumab or its excipients, Chinese hamster ovary cell products or other recombinant humanized antibodies, or to any planned chemotherapy
• Pregnant or lactating females
• History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Chu D'Amiens

Amiens, , France

HOPITAL JEAN MINJOZ; Oncologie

Besançon, , France

Institut Bergonie; Oncologie

Bordeaux, , France

Centre Francois Baclesse; Chir Gynecologique

Caen, , France

Centre Jean Perrin; Chir Generale Oncologie

Clermont-Ferrand, , France

Centre Oscar Lambret; Cancerologie Gynecologique

Lille, , France

Institut J Paoli I Calmettes; Chir II

Marseille, , France

Centre Val Aurelle Paul Lamarque; Chir A1

Montpellier, , France

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, , France

Institut Curie; Chir Generale Gyneco Oncologique

Paris, , France

Hop Europeen Georges Pompidou; Gynecologie

Paris, , France

HOPITAL TENON; Cancerologie Medicale

Paris, , France

Centre Rene Huguenin; Chir Generale Oncologique

Saint-Cloud, , France

Hopital Rangueil; CHIR Generale Et Gynecologique

Toulouse, , France

Institut Gustave Roussy; Departement Chirurgie Generale /Unite Tarn

Villejuif, , France

Countries

France

References

Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type: DERIVED

PMID: 37185961 (View on PubMed)

Other Identifiers

2012-001144-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML28337

Identifier Type: -

Identifier Source: org_study_id