A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin and Paclitaxel Plus Concurrent Bevacizumab (NSC # 704865, IND #7921) Followed By Placebo, Versus Carboplatin and Paclitaxel Plus Concurrent and Extended Bevacizumab, in Women With Newly Diagnosed, Previously Untreated, Suboptimal Advanced Stage Epithelial Ovarian, Primary Peritoneal Cancer, or Fallopian Tube Cancer

Inclusion Criteria:

- Histologically confirmed ovarian epithelial, primary peritoneal*, or fallopian tube
cancer

- Stage III with any gross (macroscopic or palpable) residual disease OR stage IV
disease

- The following histologic epithelial cell types are allowed provided the histologic
features of the tumor are compatible with a primary müllerian epithelial
adenocarcinoma:

- Serous adenocarcinoma

- Endometrioid adenocarcinoma

- Mucinous adenocarcinoma

- Undifferentiated carcinoma

- Clear cell adenocarcinoma

- Mixed epithelial carcinoma

- Transitional cell carcinoma

- Malignant Brenner tumor

- Adenocarcinoma not otherwise specified

- No borderline ovarian epithelial tumor (formerly "tumors of low malignant potential")

- Prior diagnosis of a borderline tumor that was surgically resected and an
unrelated, new, invasive ovarian epithelial or primary peritoneal cancer that
subsequently develops is allowed provided there was no prior chemotherapy for
any ovarian tumor

- No recurrent invasive ovarian epithelial cancer treated with surgery only (e.g.,
stage IA or IB low-grade epithelial ovarian or fallopian tube cancer)

- No synchronous primary endometrial cancer or prior primary endometrial cancer unless
all of the following criteria are met:

- Stage ≤ IB

- Superficial myometrial invasion without vascular or lymphatic invasion

- No poorly differentiated subtypes (i.e., papillary serous, clear cell, or other
FIGO grade 3 lesions)

- Must have undergone surgery for ovarian epithelial, primary peritoneal, or fallopian
tube cancer in the past 1-12 weeks AND have tissue available for histologic
evaluation

- Patients with stage III disease in which the largest maximal diameter of any
residual tumor implant a the completion of initial surgery is ≤ 1 cm will be
defined as "optimal" (all others will be defined as "suboptimal")

- Measurable or nonmeasurable disease

- No tumor involving active major vessels

- No prior or concurrent CNS disease, including primary brain tumor or brain metastases

- Performance status - GOG 0-2

- Absolute neutrophil count ≥ 1,500/mm^3 without induction or support by granulocyte
colony stimulating factors

- Platelet count ≥ 100,000/mm^3

- No active bleeding

- No known bleeding disorder or coagulopathy

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- SGOT ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- INR ≤ 1.5 (2-3 with stable-dose therapeutic warfarin for management of venous
thrombosis including pulmonary thromboembolus)

- PTT < 1.2 times ULN

- No acute hepatitis

- Creatinine ≤ 1.5 times ULN

- Urine protein:creatinine ratio < 1.0

- Urine protein < 1 g/24-hr urine collection

- No New York Heart Association class II-IV congestive heart failure

- No myocardial infarction or unstable angina within the past 6 months

- No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg)

- No serious cardiac arrhythmia requiring medication except for patients with
asymptomatic atrial fibrillation with a controlled ventricular rate

- No other clinically significant cardiovascular disease

- No clinically significant peripheral vascular disease ≥ grade 2

- No history of cerebral vascular accident, transient ischemic attack, or subarachnoid
hemorrhage within the past 6 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment

- No neuropathy (sensory and motor) > grade 1

- No known hypersensitivity to Chinese hamster ovary cell products or recombinant human
or humanized antibodies

- No other malignancy within the past 5 years except nonmelanoma skin cancer

- No active infection that requires parenteral antibiotics

- No serious nonhealing wound, ulcer, or bone fracture

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 28 days

- Granulating incisions healing by secondary intention with no evidence of fascial
dehiscence or infection are allowed

- No other pathological condition that would confer a high risk of bleeding

- No uncontrolled seizures

- No significant traumatic injury within the past 4 weeks

- No clinical symptoms or signs of gastrointestinal obstruction that require parenteral
hydration and/or nutrition

- No other medical history or condition that, in the opinion of the investigator, would
preclude study participation

- No prior targeted therapy for ovarian epithelial or peritoneal primary cancer,
including, but not limited to, any of the following:

- Vaccines

- Antibodies

- Tyrosine kinase inhibitors

- No prior bevacizumab

- No other prior antivascular endothelial growth factors (VEGF)

- No other concurrent biologic therapy

- No other concurrent cytotoxic or anticancer therapy

- No prior chemotherapy for abdominal or pelvic tumor including neoadjuvant
chemotherapy for their ovarian or primary peritoneal cancer

- More than 3 years since prior adjuvant chemotherapy for localized breast cancer AND
patient remains free of recurrent or metastatic disease

- No other concurrent chemotherapy

- Ovarian estrogen with or without progestin replacement therapy as indicated at the
lowest effective dose(s) for control of menopausal symptoms at any time allowed

- No progestins for management of anorexia while on study-directed therapy or
prior to disease progression

- No prior hormonal therapy for ovarian, peritoneal primary, or fallopian tube cancer

- No concurrent hormonal therapy

- More than 3 years since prior radiotherapy for localized cancer of the breast, head
and neck, or skin AND patient remains free of recurrent or metastatic disease

- No prior radiotherapy to the abdominal cavity or pelvis

- No concurrent radiotherapy

- No concurrent amifostine or other protective reagents

- At least 4 weeks since prior major surgical procedure or open biopsy

- At least 1 week since prior core biopsy

- No concurrent major surgery including abdominal surgery (laparotomy or laparoscopy)
prior to disease progression (e.g., colostomy or enterostomy reversal, interval or
secondary cytoreductive surgery, or second look surgery

- No prior cancer therapy that would preclude study treatment

- No concurrent consolidation or maintenance therapy