Clinical trial NCT00262847
Conditions: Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Malignant Ovarian Mixed Epithelial Tumor Ovarian Brenner Tumor Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Adenocarcinoma Ovarian Serous Adenocarcinoma Ovarian Transitional Cell Carcinoma Primary Peritoneal Serous Adenocarcinoma Stage IIIA Fallopian Tube Cancer Stage IIIA Ovarian Cancer Stage IIIA Primary Peritoneal Cancer Stage IIIB Fallopian Tube Cancer Stage IIIB Ovarian Cancer Stage IIIB Primary Peritoneal Cancer Stage IIIC Fallopian Tube Cancer Stage IIIC Ovarian Cancer Stage IIIC Primary Peritoneal Cancer Stage IV Fallopian Tube Cancer Stage IV Ovarian Cancer Stage IV Primary Peritoneal Cancer Undifferentiated Fallopian Tube Carcinoma Undifferentiated Ovarian Carcinoma
Sponsor: National Cancer Institute (NCI)
Start date: 2005-09-01; Completion date: 2015-04-01
Enrollment: 1873 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Patients receive paclitaxel 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 2: 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 3: 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.
Interventions: intervention 1: Bevacizumab intervention 2: Carboplatin intervention 3: Laboratory Biomarker Analysis intervention 4: Paclitaxel intervention 5: Placebo intervention 6: Quality-of-Life Assessment
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Correlative studies intervention 4: Given IV intervention 5: Given IV intervention 6: Ancillary studies

Protocol documents: