A Randomized Phase III Trial of Cisplatin Plus Paclitaxel With and Without NCI-Supplied Bevacizumab (NSC #704865, IND #113912) Versus the Non-Platinum Doublet, Topotecan Plus Paclitaxel, With and Without NCI-Supplied Bevacizumab, In Stage IVB, Recurrent or Persistent Carcinoma of the Cervix

Inclusion Criteria:

- Histologically confirmed carcinoma of the cervix, including any of the following
subtypes:

- Squamous cell carcinoma

- Adenosquamous cell carcinoma

- Adenocarcinoma

- Primary stage IVB, recurrent, or persistent disease not amenable to curative
treatment with surgery and/or radiotherapy

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques or ≥ 10 mm by spiral CT scan

- Biopsy confirmation required if target lesion(s) measures < 30 mm or if the
treating physician determines it is clinically indicated

- Has ≥ 1 "target lesion" that can be used to assess response

- Tumors within a previously irradiated field are designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence ≥ 90 days following completion of radiotherapy

- No history or evidence of CNS disease, including primary brain tumor, brain
metastases, or craniospinal metastases

- GOG performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times normal

- SGOT ≤ 2.5 times normal

- Alkaline phosphatase ≤ 2.5 times normal

- PT/INR ≤ 1.5 (or in-range INR, if patient is on a stable dose of therapeutic warfarin
for management of venous thrombosis, including pulmonary thromboembolus)

- PTT < 1.2 times upper limit of normal

- Serum creatinine normal OR creatinine clearance ≥ 60 mL/min

- Urine protein:creatinine ratio 1.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

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

- No active infection requiring antibiotics

- No significant traumatic injury within the past 28 days

- No serious non-healing wound, ulcer, or bone fracture

- Patients with granulating incisions healing by secondary intention are eligible
provided there is no evidence of fascial dehiscence or infection AND the wound
is examined weekly

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 3-6 months

- Patients must have undergone correction (or spontaneous healing) of the
perforation/fistula and/or the underlying process causing the
fistula/perforation

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

- No active bleeding or pathologic condition that carries a high risk of bleeding
(e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)

- No seizures not controlled with standard medical therapy

- No cerebrovascular accident (i.e., stroke), transient ischemic attack, or
subarachnoid hemorrhage within the past 6 months

- No clinically significant cardiovascular disease, including any of the following:

- Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP >
90 mm Hg

- Myocardial infarction or unstable angina within the past 6 months

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Atrial fibrillation allowed provided it is asymptomatic and ventricular
rate is controlled

- Significant peripheral vascular disease (i.e., ≥ grade 2 peripheral vascular
disease, as defined by NCI CTCAE v3.0 criteria)

- No bilateral hydronephrosis that cannot be alleviated by ureteral stents or
percutaneous drainage

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

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

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

- No peripheral neuropathy ≥ grade 2

- Recovered from all prior therapy

- No prior anti-cancer therapy that would preclude study therapy

- No prior anti-VEGF drugs, including bevacizumab

- No prior chemotherapy unless given concurrently with radiotherapy

- Prior paclitaxel and/or topotecan with radiotherapy not allowed

- At least 6 weeks since prior chemoradiotherapy

- At least 3 weeks since prior radiotherapy alone

- More than 28 days since prior major surgery or open biopsy

- More than 7 days since prior core biopsy

- No concurrent major surgery including, but not limited to, abdominal surgery prior to
disease progression (e.g., colostomy or enterostomy reversal, interval or secondary
cytoreductive surgery, or second-look surgery via laparotomy or laparoscopy)