A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel (or Gemcitabine) Alone or in Combination With Bevacizumab (NSC #704865) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Peritoneal Primary and Fallopian Tube Cancer. NCI-Supplied Agents: Bevacizumab (NSC #704865)

Brief Summary

Detailed Description

PRIMARY OBJECTIVES: I. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases the duration of overall survival in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer. II. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases the duration of overall survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer. SECONDARY OBJECTIVES: I. To determine if the addition of bevacizumab to the second-line and maintenance phase of treatment increases the duration of progression-free survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer. II. To prospectively determine the incidence of carboplatin and paclitaxel hypersensitivity in these patients undergoing retreatment with both agents as first recurrence therapy. III. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases quality of life (QOL) in patients with recurrent platinum-sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer, as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) trial outcome index and Rand Short Form (SF)-36 physical functioning scale. IV. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases QOL relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum-sensitive epithelial ovarian, peritoneal primary or fallopian tube cancer. TRANSLATIONAL RESEARCH OBJECTIVES: I. To define molecular and biochemical profiles associated with the duration of progression-free survival in platinum-sensitive recurrent ovarian, peritoneal primary or fallopian tube carcinoma treated with combination chemotherapy with or without bevacizumab followed with or without maintenance bevacizumab therapy in the presence or absence of secondary surgical cytoreduction. II. To identify molecular determinants that predict sensitivity or resistance to carboplatin and paclitaxel with or without bevacizumab followed with or without maintenance bevacizumab therapy. III. To bank deoxyribonucleic acid (DNA) from whole blood for research and evaluate the association between single nucleotide polymorphisms (SNPs) and measures of clinical outcome including overall survival, progression-free survival and adverse events. OUTLINE: Patients are assigned to 1 of 4 treatment groups. Patients who are not candidates for surgical cytoreduction (i.e., those for whom complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking) are eligible to receive chemotherapy after randomization. Patients who are eligible for surgery undergo abdominal exploration with cytoreduction. Patients are then randomized to 1 of 4 treatment arms. ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours or docetaxel IV over 1 hour and carboplatin IV over 60 minutes on day 1. ARM II: Patients receive chemotherapy as in Arm I and bevacizumab IV over 30-90 minutes on day 1. ARM III: Patients receive gemcitabine hydrochloride IV over 60 minutes on days 1 and 8 and carboplatin as in Arm I. ARM IV: Patients receive gemcitabine hydrochloride IV as in Arm III, bevacizumab IV and carboplatin IV as in Arm II. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with measurable disease achieving a clinical response (CR) receive 6-8 courses of therapy. Patients with stable disease or partial regression receive a maximum of 8 courses. Patients without measurable lesions as determined by a computed tomography (CT) scan prior to initiating study treatment continue therapy for 6 courses or, if cancer antigen (CA)-125 normalizes, for 2 courses beyond CA-125 normalization, whichever is greater. Patients in Arm II then receive a maintenance regimen comprising bevacizumab IV over 30-90 minutes. Treatment with bevacizumab alone repeats every 3 weeks 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 yearly for 5 years.

Primary Outcomes

Secondary Outcomes

• Progression-free Survival (Chemotherapy Analysis)(Radiographic assessment of disease was conducted during chemotherapy and then every 6 months during the maintenance / surveillance phase)
• Summary of Adverse Events (CTCAE Version 4.0)(During treatment period and up to 100 days after stopping the study treatment, a median duration of 82.5 months)
• Patient Reported Quality of Life (Chemotherapy Analysis)(1. Prior to cycle 1 (baseline), 2. Prior to cycle 3 (6 weeks post cycle 1), 3. Prior to cycle 6 (15 weeks post cycle 1), 4. 6 months post cycle 1, 5. 12 months post cycle 1.)
• Progression Free Survival (Surgery Analysis)(Radiographic assessment of disease (in patients with measurable and non-measurable disease) was conducted Every three months for two years and then every 6 months after completion of chemotherapy during the maintenance/surveillance phase.)
• Patient Reported Physical Function (Chemotherapy Analysis)(1. Prior to cycle 1 (baseline), 2. Prior to cycle 3 (6 weeks post cycle 1), 3. Prior to cycle 6 (15 weeks post cycle 1), 4. 6 months post cycle 1, 5. 12 months post cycle 1.)
• Patient Reported Quality of Life (Surgery Analysis)(1. Prior to surgery, 2. 6 weeks post-surgery, 3. 15 weeks post-surgery, 4. 6 months post-surgery, 5. 12 months post-surgery.)
• Patient Reported Physical Functioning (Surgery Analysis)(1. Prior to surgery (baseline), 2. 6 weeks post-surgery, 3. 15 weeks post-surgery 4. 6 months post-surgery, 5. 12 months post-surgery)