A Randomized, Open-Label, Phase II Study Assessing the Efficacy and the Safety of Bevacizumab in Neoadjuvant Therapy in Patients With FIGO Stage IIIC/IV Ovarian, Tubal or Peritoneal Adenocarcinoma, Initially Unresectable
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 99
- Locations
- 15
- Primary Endpoint
- Percentage of Participants with Different CC Scores After IDS
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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).
Intervention: Carboplatin (Drug)
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).
Intervention: Paclitaxel (Drug)
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).
Intervention: Bevacizumab (Drug)
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.
Intervention: Carboplatin (Drug)
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.
Intervention: Paclitaxel (Drug)
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.
Intervention: Bevacizumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants with Different CC Scores After IDS
Time Frame: After IDS (approximately 4 months from randomization)
Percentage of Participants with Complete Resection After IDS
Time Frame: After IDS (approximately 4 months from randomization)
Secondary Outcomes
- Percentage of Participants with Response According to Cancer Antigen (CA)-125 Levels(At IDS (approximately 3 months); at Cycle 26 (approximately 22 months); and at last CA-125 assessment (up to approximately 38 months))
- Percentage of Participants with RECIST v1.1 Objective Response and CA-125 Response(At Cycle 26 (approximately 22 months) and at last response assessment (up to approximately 38 months))
- Number of Participants with Disease Progression or Death From any Cause(From Baseline to disease progression or death due to any cause (up to approximately 38 months))
- Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(At IDS (approximately 3 months); at Cycle 26 (approximately 22 months); and at last tumor assessment (up to approximately 38 months))
- Percentage of Participants with RECIST v1.1 Objective Response Without CA-125 Response(At Cycle 26 (approximately 22 months) and at last response assessment (up to approximately 38 months))
- Percentage of Participants with CA-125 Response Without RECIST v1.1 Objective Response(At Cycle 26 (approximately 22 months) and at last response assessment (up to approximately 38 months))
- Progression-Free Survival (PFS) According to RECIST v1.1(From Baseline to disease progression or death due to any cause (up to approximately 38 months))
- Percentage of Participants with Serious Adverse Events (SAEs) and Non-SAEs(SAEs: from randomization up to last assessment (up to approximately 38 months); non-SAEs: from Day 1 up to 28 days after last dose (up to approximately 23 months))