Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

Inclusion Criteria:

• Primary Surgery and Neoadjuvant Chemotherapy with Interval Cytoreductive SurgeryPatients:

• Patients must have measurable disease; at least one target lesion must have aminimum length of 1 cm in both the long and short axis (determined at the localsite); for primary surgery patients, if no radiographic evidence of measurabledisease is obtained prior to registration this can be based on surgical findings;imaging then would need to be completed in the 14 days between Gynecology OncologyGroup (GOG) registration and chemotherapy initiation

• After GOG registration, the American College of Radiology [ACR] Imaging CoreLaboratory will confirm target lesion as required per protocol; theGOG-eligibility (RECIST) scan and baseline T0 perfusion CT scans will bereviewed prior to the intermediate T1 perfusion CT time point

• Primary Surgery Patients:

• Patients with a histologic diagnosis of epithelial ovarian cancer, peritonealprimary carcinoma or fallopian tube cancer, stage II -IV suboptimally debulked (anyresidual disease > 1 cm); International Federation of Gynecology and Obstetrics (FIGO) stage is assessed following the completion of initial abdominal surgery,appropriate imaging studies and with appropriate tissue available for histologicevaluation; the minimum surgery required is an abdominal surgery providing tissuefor histologic evaluation and establishing and documenting the primary site andstage; if additional surgery was performed, it should have been in accordance withappropriate surgery for ovarian or peritoneal carcinoma described in the GOGSurgical Procedures Manual

• Neoadjuvant Chemotherapy (NAC) with Interval Cytoreductive Surgery (ICS) Patients:

• For patients undergoing NAC-ICS, a core tissue (not fine needle aspiration) biopsyis required; the tissue must be consistent with a Müllerian origin; patients willrequire documentation of at least stage II or extraovarian sites of disease acquiredvia imaging or surgery (without attempt at cytoreduction)

• Patients with the following histologic epithelial cell types are eligible: serous,endometrioid, clear cell, mucinous adenocarcinoma, undifferentiated carcinoma, mixedepithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, oradenocarcinoma not otherwise specified (N.O.S.); however, the histologic features ofthe tumor must be compatible with a primary Müllerian epithelial adenocarcinoma;patients may have co-existing fallopian tube carcinoma in-situ so long as theprimary origin of invasive tumor is ovarian, peritoneal or fallopian tube; of note,patients with clear cell and mucinous tumors will be eligible unless there is ahigher priority protocol

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl; this ANC cannothave been induced or supported by granulocyte colony stimulating factors

• Platelets greater than or equal to 100,000/mcl

• Creatinine =< 1.5 x institutional upper limit normal (ULN)

• Bilirubin less than or equal to 1.5 x ULN

• Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Neuropathy (sensory or motor) less than or equal to Common Terminology Criteria forAdverse Events (CTCAE) grade 1

• Patients must have a GOG performance status of 0, 1, or 2

• Patients must be entered within 12 weeks of diagnostic/staging surgery

• Patients who have met the pre-entry requirements

• An approved informed consent and authorization permitting release of personal healthinformation and must be signed by the patient or guardian

• Only applies for patients who elect to receive bevacizumab:

• Patients in this trial may receive ovarian estrogen +/- progestin replacementtherapy as indicated at the lowest effective dose(s) for control of menopausalsymptoms at any time, but not high-dose progestins for management of anorexiawhile on protocol-directed therapy or prior to disease progression due tothrombophlebitis risk

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable doseof therapeutic warfarin for management of venous thrombosis including pulmonarythromboembolus) and a partial prothrombin time (PTT) < 1.2 times the upperlimit of normal; (heparin, lovenox or alternative anticoagulants areacceptable)

• All patients enrolled into GOG-0262 at sites where ACRIN 6695 is open will beenrolled in the advanced imaging protocol; patients receiving adjuvant orneoadjuvant chemotherapy are eligible for ACRIN 6695; the following sentencedoes not apply to those patients entered after 02/08/2012: if a patientdeclines to participate in the perfusion imaging portion of the protocol, aclinical rationale for declination of imaging form will be completed as part ofthe data submission for ACRIN 6695

• ACRIN 6695 Eligible Patients:

• Confirmation of ACRIN 6695 eligibility after the baseline T0 perfusion computedtomography (CT) will be assessed by the ACR Imaging Core Lab: At least onetarget lesion must have a minimum length of 1 cm in both the long and shortaxis (as determined by the local site), at least half of the target lesion musthave attenuation greater than or equal to 10 Hounsfield Units (HU) on theunenhanced CT, and at least half of the lesion must have maximum enhancementgreater than or equal to 5 HU in the perfusion CT scan (as determined by theACR Imaging Core Lab)

Exclusion Criteria:

• Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian,primary peritoneal or fallopian tube cancer treated with surgery only (such aspatients with stage I-A or I-B low grade epithelial ovarian or fallopian tubecancers) are not eligible; patients with a prior diagnosis of a borderline tumorthat was surgically resected and who subsequently develop an unrelated, new invasiveepithelial ovarian, peritoneal primary or fallopian tube cancer are eligible,provided that they have not received prior chemotherapy for any ovarian tumor

• Patients who have received prior radiotherapy to any portion of the abdominal cavityor pelvis; prior radiation for localized cancer of the breast, head and neck, orskin is permitted, provided that it was completed more than three years prior toregistration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumorincluding neo-adjuvant chemotherapy for their ovarian, primary peritoneal orfallopian tube cancer; patients may have received prior adjuvant chemotherapy forlocalized breast cancer, provided that it was completed more than three years priorto registration, and that the patient remains free of recurrent or metastaticdisease

• Patients who have received any targeted therapy (including but not limited tovaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for managementof their epithelial ovarian, fallopian tube or peritoneal primary cancer

• Patients with synchronous primary endometrial cancer, or a past history of primaryendometrial cancer, unless all of the following conditions are met: stage notgreater than I-A, grade 1 or 2, no more than superficial myometrial invasion,without vascular or lymphatic invasion; no poorly differentiated subtypes, includingpapillary serous, clear cell or other FIGO grade 3 lesions

• With the exception of non-melanoma skin cancer, patients with other invasivemalignancies who had (or have) any evidence of the other cancer present within thelast five years or whose previous cancer treatment contraindicates this protocoltherapy

• Patients with acute hepatitis or active infection that requires parenteralantibiotics

• Patients with clinically significant cardiovascular disease; this includes:

• Myocardial infarction or unstable angina < 6 months prior to registration

• New York Heart Association (NYHA) grade II or greater congestive heart failure

• Serious cardiac arrhythmia requiring medication; this does not includeasymptomatic, atrial fibrillation with controlled ventricular rate

• Patients who are pregnant or nursing; patients of childbearing potential must agreeto use contraceptive measures during study therapy and for at least six months aftercompletion of bevacizumab therapy

• Patients who have received prior therapy with any anti-vascular endothelial growthfactor (VEGF) drug, including bevacizumab

• Patients with medical history or conditions not otherwise previously specified whichin the opinion of the investigator should exclude participation in this study; theinvestigator should feel free to consult the Statistical and Data Center (SDC)randomization desk for uncertainty in this regard

• Patients with known allergy to cremophor or polysorbate 80

• Only applies to patients who elect to receive bevacizumab:

• Patients with serious non-healing wound, ulcer, or bone fracture; this includeshistory of abdominal fistula, gastrointestinal perforation or intra-abdominalabscess within 28 days; patients with granulating incisions healing by secondaryintention with no evidence of fascial dehiscence or infection are eligible butrequire weekly wound examinations

• Patients with active bleeding or pathologic conditions that carry high risk ofbleeding, such as known bleeding disorder, coagulopathy, or tumor involving majorvessels

• Patients with history or evidence upon physical examination of central nervoussystem (CNS) disease, including primary brain tumor, seizures not controlled withstandard medical therapy, any brain metastases, or history of cerebrovascularaccident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhagewithin six months of the first date of treatment on this study

• Patients with CTCAE grade 2 or greater peripheral vascular disease (at leastbrief [< 24 hours] episodes of ischemia managed non-surgically and withoutpermanent deficit)

• Patients with a history of CVA within six months

• Patients with known hypersensitivity to Chinese hamster ovary cell products or otherrecombinant human or humanized antibodies

• Patients with clinically significant proteinuria; urine protein should be screenedby urine protein-creatinine ratio (UPCR); the UPCR has been found to correlatedirectly with the amount of protein excreted in a 24 hour urine collection;specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24-hour urinecollection; obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24-hour urine); send sample to lab with request for urineprotein and creatinine levels (separate requests); the lab will measure proteinconcentration (mg/dL) and creatinine concentration (mg/dL); the UPCR is derived asfollows: protein concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR < 1.0 to allow participation in the study

• Patients with or with anticipation of invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28days prior to the first date of bevacizumab therapy (cycle 2)

• Major surgical procedure anticipated during the course of the study; thisincludes, but is not limited to abdominal surgery (laparotomy or laparoscopy)prior to disease progression such as colostomy or enterostomy reversal,secondary cytoreductive surgery, or second look surgery; please consult withthe SDC Randomization Desk prior to patient entry for any questions related tothe classification of surgical procedures

• Any tissue biopsy, such as a core biopsy, within 7 days prior to the first dateof bevacizumab therapy (cycle 2)

• Patients with clinical symptoms or signs of gastrointestinal obstruction and whorequire parenteral hydration and/or nutrition

• Patients with metastasis tumor in the parenchyma of the liver or lungs withproximity to large vessels which could make the patients at high risk of lethalhemorrhage during treatment with bevacizumab (ie. hemoptysis, liver rupture)

• ACRIN 6695 Ineligible Patients:

• Patients with contraindication to iodinated contrast for perfusion CT imaging

• Patients who receive Metformin within 48 hours before perfusion CT imaging