This randomized phase II trial studies how well bevacizumab with or without everolimus works in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and everolimus may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without everolimus in treating ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
PRIMARY OBJECTIVES: I. To estimate the progression-free survival hazard ratio of the combination of oral everolimus (RAD001) and bevacizumab compared to oral placebo and bevacizumab in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer. SECONDARY OBJECTIVES: I. To determine the nature and degree of toxicity of oral everolimus (or placebo) plus bevacizumab. II. To characterize and compare progression-free survival and overall survival in patients with measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) and patients with detectable (non-measurable) disease. III. To estimate the proportion of patients with measurable disease who have objective tumor responses by treatment. IV. To provide descriptive information about cancer antigen (CA)-125 responses by regimen and where possible by objective tumor responses. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and everolimus orally (PO) once daily (QD) on days 1-28. ARM II: Patients receive bevacizumab as in Arm I and placebo PO QD on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
150
Gynecologic Oncology Group of Arizona
Phoenix, Arizona, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
University of Colorado Hospital
Aurora, Colorado, United States
Progression-free Survival
The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as an 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Duration of time from start of treatment to time of progression, approximately 4 years and 6 months.
Incidence of Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0)
Number of participants with a grade of 3 or higher during the treatment period.
Time frame: All Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during treatment and up to 30 days after stopping the study treatment, approximately 4 years and 6 months.
Characterize and Compare Progression-free Survival and Overall Survival in Patients With Measurable Disease (RECIST Criteria) and Patients With Detectable (Non-measurable) Disease
Progression-free survival and overall survival broken down by measurable disease status
Time frame: Continued until disease progression, assessed up to approximately 4 years and 6 months
The Proportion of Patients With Measurable Disease Who Have Objective Tumor Responses by Treatment.
Complete and Partial Tumor Response by RECIST 1.0
Time frame: Up to approximately 4 years and 6 months
Percentage of Participants With at Least One Cancer Antigen 125 (CA-125) Response
Response as evaluated by CA-125 levels.A CA 125 test measures the amount of the protein CA 125 (cancer antigen 125) in blood.CA 125 is a tumor marker recommended for clinical use in the diagnosis and management of ovarian cancer. CA-125 responses were assessed with Rustin criteria. Initial values had to be 2x ULN (upper limit of normal) within 2 weeks of starting therapy to be considered evaluable.Patient were evaluated by using best overall response while receiving study therapy.
Time frame: Prior to each cycle of treatment. Then follow-up every three months for 2 years , then every 6 months for 3 years. Duration was approximately 4 years and 6 months.
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The Hospital of Central Connecticut
New Britain, Connecticut, United States
Rush University Medical Center
Chicago, Illinois, United States
Sudarshan K Sharma MD Limited-Gynecologic Oncology
Hinsdale, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
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