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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01739218
First received: November 28, 2012
Last updated: August 1, 2016
Last verified: August 2016
  Purpose
This randomized, open-label study will evaluate the efficacy and safety of neoadjuvant Avastin (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 Avastin 15 milligrams per kilogram (mg/kg) intravenously every 3 weeks in Cycles 1 to 3 before surgery. All participants will receive Avastin 15 mg/kg intravenously every 3 weeks for Cycles 6 to 26. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs, for up to a maximum of 26 cycles.

Condition Intervention Phase
Ovarian Cancer
Drug: Bevacizumab
Drug: Carboplatin
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants with Complete Resection After Interval Debulking Surgery (IDS), Defined as Complete Removal of All Macroscopic Residual Tumor at IDS Defined as Completeness of Cytoreduction (CC) Score Equal to (=) 0 [ Time Frame: After IDS (approximately 3 months from randomization) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with Objective Response Before IDS (Neoadjuvant Phase) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and/or Cancer Antigen (CA)-125 Levels [ Time Frame: From Baseline to IDS (approximately 3 months) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Objective Response After All Courses of Treatment According to RECIST Version 1.1 and/or CA-125 Levels [ Time Frame: From IDS (approximately 3 months after randomization) to end of treatment (approximately 16 months overall) ] [ Designated as safety issue: No ]
  • Progression-Free Survival According to RECIST Version 1.1 [ Time Frame: From Baseline to disease progression or death (up to approximately 4 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events [ Time Frame: From Baseline to 28 days after last dose (up to approximately 2 years) ] [ Designated as safety issue: No ]

Enrollment: 99
Study Start Date: February 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neoadjuvant Carboplatin/Paclitaxel Plus 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 adjuvant treatment periods in Cycles 1 to 26 (no treatment in Cycles 4 and 5).
Drug: Bevacizumab
Participants will receive bevacizumab as 15 mg/kg IV every 3 weeks on Day 1 of Cycles 1 to 3 and Cycles 6 to 26. The investigational arm will receive bevacizumab during both treatment periods; however, no bevacizumab will be administered to the control arm during Cycles 1 to 3.
Other Name: Avastin
Drug: Carboplatin
Carboplatin will be dosed according to the Calvert formula using the participant's glomerular filtration rate multiplied by the target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min), and given IV every 3 weeks on Day 1 of Cycles 1 to 8.
Drug: Paclitaxel
Paclitaxel will be given as 175 milligrams per meter-squared (mg/m^2) IV every 3 weeks on Day 1 of Cycles 1 to 8. Alternatively, the regimen may be adjusted to 80 mg/m^2 weekly during Cycles 5 to 8.
Active Comparator: Neoadjuvant Carboplatin/Paclitaxel Without 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 only be administered during the adjuvant treatment period in Cycles 6 to 26.
Drug: Bevacizumab
Participants will receive bevacizumab as 15 mg/kg IV every 3 weeks on Day 1 of Cycles 1 to 3 and Cycles 6 to 26. The investigational arm will receive bevacizumab during both treatment periods; however, no bevacizumab will be administered to the control arm during Cycles 1 to 3.
Other Name: Avastin
Drug: Carboplatin
Carboplatin will be dosed according to the Calvert formula using the participant's glomerular filtration rate multiplied by the target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min), and given IV every 3 weeks on Day 1 of Cycles 1 to 8.
Drug: Paclitaxel
Paclitaxel will be given as 175 milligrams per meter-squared (mg/m^2) IV every 3 weeks on Day 1 of Cycles 1 to 8. Alternatively, the regimen may be adjusted to 80 mg/m^2 weekly during Cycles 5 to 8.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult females greater than or equal to (>/=) 18 years of age
  • 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 >/=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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739218

Locations
France
Amiens, France, 80054
Besancon, France, 25030
Bordeaux, France, 33076
Caen, France, 14076
Clermont Ferrand, France, 63011
Lille, France, 59020
Marseille, France, 13273
Montpellier, France, 34298
Nice, France, 06189
Paris, France, 75231
Paris, France, 75908
Paris, France, 75970
St Cloud, France, 92210
Toulouse, France, 31059
Villejuif, France, 94805
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01739218     History of Changes
Other Study ID Numbers: ML28337  2012-001144-22 
Study First Received: November 28, 2012
Last Updated: August 1, 2016
Health Authority: France: Agence Nationale de Securite du Medicament (ANSM)

Additional relevant MeSH terms:
Bevacizumab
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2016