This randomized phase III trial studies carboplatin, paclitaxel, and bevacizumab to see how well they work compared to carboplatin, paclitaxel, and placebo in treating patients with stage III or stage IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether carboplatin, paclitaxel, and bevacizumab are more effective than carboplatin, paclitaxel, and placebo in treating ovarian epithelial, primary peritoneal, or fallopian tube cancer.
PRIMARY OBJECTIVE: I. To determine if the addition of 5 concurrent cycles of bevacizumab to 6 cycles of standard therapy (carboplatin and paclitaxel) (Arm II) increases the duration of progression-free survival (PFS) when compared to 6 cycles of standard therapy alone (Arm I) in women with newly diagnosed stage III (with any gross residual disease) and stage IV, epithelial ovarian, peritoneal primary or fallopian tube cancer. II. To determine if the addition of 5 concurrent cycles of bevacizumab plus extended bevacizumab for 16 cycles beyond the 6 cycles of standard therapy (carboplatin and paclitaxel) (Arm III) increases progression-free survival when compared to 6 cycles of standard therapy (Arm I) in women with newly diagnosed stage III (with any gross residual disease) and stage IV, epithelial ovarian, peritoneal primary or fallopian tube cancer. SECONDARY OBJECTIVES: I. In the event that both Arm II and Arm III regimens are superior to the Arm I regimen with respect to progression-free survival, to determine whether the Arm III regimen prolongs progression-free survival when compared to the Arm II regimen. II. To determine whether the Arm II or Arm III regimen increases the duration of overall survival when compared with the Arm I regimen. III. To compare each of the experimental regimens to the Arm I regimen with respect to the incidence of severe toxicities or serious adverse events. IV. To determine the impact on Quality of Life (QOL, as measured by the Functional Assessment of Cancer Therapy-Ovarian \[FACT-O\] trial outcome index \[TOI\]) following treatment with the above regimens. TERTIARY OBJECTIVES: I. To assess the relationship between angiogenic markers and clinical outcome including tumor response, progression-free survival and overall survival in patients randomized to standard cytotoxic chemotherapy (paclitaxel and carboplatin) without bevacizumab, with concurrent bevacizumab or with extended bevacizumab. II. To assess the predictive value of a set of genes whose expression correlates with survival of patients with stage III (with any gross residual disease) and stage IV, epithelial ovarian, peritoneal primary or fallopian tube cancer. III. To bank whole blood for research. IV. To determine if genetic variations in genes associated with essential hypertension including WNK lysine deficient protein kinase 1 (WNK1), G protein-coupled receptor kinase 4 (GRK4) and kallikrein B (KLKB1) predict which patients are likely to develop bevacizumab-induced hypertension. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Beginning in course 2, patients also receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses. Beginning in course 7, patients receive placebo alone IV over 30-90 minutes on day 1. Treatment with placebo repeats every 21 days for up to 22 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive paclitaxel and carboplatin as in arm I. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses. Beginning in course 7, patients receive placebo alone IV over 30-90 minutes on day 1. Treatment with placebo repeats every 21 days for up to 22 courses in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive paclitaxel and carboplatin as in arm I. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses. Beginning in course 7, patients receive bevacizumab alone IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 22 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
1,873
Given IV
Given IV
Correlative studies
Given IV
Given IV
Ancillary studies
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Clearview Cancer Institute
Huntsville, Alabama, United States
Mobile Infirmary Medical Center
Mobile, Alabama, United States
Banner Thunderbird Medical Center
Glendale, Arizona, United States
Progression-free Survival
Median progression-free survival (PFS). Onset of progression could be based on radiographic (RECIST) criteria or rising CA-125 (GCIG criteria).
Time frame: From study entry until first disease progression, death or date of last contact, up to 6 years
Overall Survival
Median overall survival (OS)
Time frame: From study entry to death or last contact, up to 6 years
Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Eligible and Evaluable patients
Time frame: Up to 5 years
Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI)
Estimated least squares means from a mixed module of Quality of Life (QOL) scores at each assessment point, adjusted for baseline score and patient's age. Note: The range of possible scores of the FACT-O TOI is 0 - 104 for all treatment groups and at all visits. A higher score indicates better QOL. Baseline mean scores are raw means.
Time frame: At baseline, 9, 18, 36, 60, and 84 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Banner Desert Medical Center
Mesa, Arizona, United States
Banner Baywood Medical Center
Mesa, Arizona, United States
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States
Western Regional CCOP
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
...and 622 more locations