Carboplatin, Paclitaxel and Gemcitabine With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer

Inclusion Criteria:

• Patients must have histologic diagnosis of ovarian epithelial carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent

• The following histologic epithelial cell types are eligible:

  • Serous adenocarcinoma
  • Endometrioid adenocarcinoma
  • Mucinous adenocarcinoma
  • Undifferentiated carcinoma
  • Clear cell adenocarcinoma
  • Mixed epithelial carcinoma
  • Transitional cell carcinoma
  • Malignant Brenner Tumor
  • Adenocarcinoma not otherwise specified

• Patients must have had a complete response to front-line platinum-taxane therapy (at least 3 cycles) and a treatment-free interval without clinical evidence of progressive disease lasting at least 6 months

  • A complete response to front-line chemotherapy must include the following:

    • Negative physical exam
    • Negative pelvic exam
    • Normalization of CA125, if elevated at baseline
    • Negative radiographic assessment of disease
  • All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent
  • Front-line treatment may include maintenance therapy following complete clinical or pathological response; however, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease; patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE provided their recurrence is documented more than 6 months from primary cytotoxic chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has elapsed since their last infusion of biological therapy

• Patients must have clinically evident recurrent disease for the purpose of this study,

  • Measurable disease (RECIST) is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be more than or equal to 20 mm when measured by conventional techniques, MRI or CT, or more than or equal to 10 mm when measured by spiral CT
• Absolute neutrophil count (ANC) >= 1,500/mm^3 equivalent to Common Toxicity Criteria for Adverse Events v3.0 (CTCAE) Grade1
• Platelet count >= 100,000/mm^3 (CTCAE Grade 0-1)
• Creatinine (non-isotope dilution mass spectrometry [IDMS]) =< 1.5 times upper limit of normal (ULN)
• Total bilirubin =< 1.5 times ULN
• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) =< 2.5 times ULN (< 5.0 times ULN in the presence of liver metastasis)
• Alkaline phosphatase =< 2.5 times ULN (< 5.0 times ULN in the presence of liver metastasis)
• Patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL
• Patients who are not candidates for surgical cytoreduction are eligible for the chemotherapy randomization; patients are not considered candidates for surgical cytoreduction if complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking
• Patients must have signed an approved informed consent and authorization permitting release of personal health information
• Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

Exclusion Criteria:

• Patients who have more than one previous regimen of chemotherapy (maintenance therapy is not considered a second regimen)
• Patients receiving concurrent immunotherapy, or radiotherapy
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded
• Patients whom have already undergone secondary cytoreduction for recurrent disease are excluded
• Patients with a prior histologic diagnosis of borderline, low malignant potential (grade 0) epithelial carcinoma that was surgically resected and who subsequently developed an unrelated, new invasive epithelial ovarian or peritoneal primary cancer are eligible provided they meet the inclusion criteria above
• Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation

• Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer are excluded, unless all of the following conditions are met:

  • Stage not greater than I-B;
  • No more than superficial myometrial invasion, without vascular or lymphatic invasion;
  • No poorly differentiated subtypes, including papillary serous, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) Grade 3 lesions
• Patients with uncontrolled infection
• Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
• Patients with peripheral neuropathy >= grade 2
• Patients with a history of allergic reactions to carboplatin and/or paclitaxel or chemically similar compounds; patients with allergic (hypersensitivity) reactions to these chemotherapeutic agents are NOT excluded IF they were successfully retreated following a desensitization program or protocol
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are nursing are not eligible for this trial; to date, no fetal studies in animal or humans have been performed; the possibility of harm to a fetus is likely; bevacizumab specifically inhibits VEGF, which is responsible for the formation of new blood vessels during development, and antibodies can cross the placenta; therefore, bevacizumab should not be administered to pregnant women; in addition, there are unknown immediate and long-term consequences of chemotherapy administration to these women; in addition, surgical exploration as mandated by randomization during pregnancy may cause imminent mortal consequences; further, it is not known whether bevacizumab is excreted in human milk; because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women; subjects will be apprised of the large potential risk to a developing fetus
• Patients with other invasive malignancies, with the exception of nonmelanoma skin cancer, or patients who had (or have) any evidence of the other cancer present within the past 5 years or whose previous cancer treatment contraindicates this protocol therapy
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding such as a known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients with a history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or a history of stroke within the past 5 years of the first date of treatment on this study

• Patients with clinically significant cardiovascular disease including any of the following:

  • Significant cardiac conduction abnormalities (e.g., PR interval > 0.24 sec or 2nd or 3rd degree atrioventricular [AV] block )
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg
  • Myocardial infarction, cardiac arrhythmia, or unstable angina within the past 6 months
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Grade II or greater peripheral vascular disease except episodes of ischemia < 24 hrs in duration that are managed non-surgically and without permanent deficit
  • History of cerebrovascular accident (CVA) within the past 6 months

• Patients who have had a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment on this study:

  • Patients undergoing pre-treatment secondary cytoreduction will undergo therapy with bevacizumab on cycle 2
  • Patients undergoing pre-treatment surgery for purposes other than cytoreduction may also participate provided they meet eligibility; patients randomized to arms containing bevacizumab must wait a minimum of 28 days since that procedure to begin protocol treatment; patients who undergo an uncomplicated port placement must wait a minimum of 7 days to begin protocol treatment