Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer

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)