The purpose of this study is to determine whether the combination of topotecan, cisplatin and bevacizumab is effective in the treatment of recurrent or persistent cervical cancer

Cervical cancer remains a major cause of morbidity and mortality in women. Chemoradiation has led to improvements in survival, but the prognosis for patients with recurrent, metastatic cervical cancer remains poor. There is the need for more effective treatments for the management of recurrent/persistent cervical cancer. Angiogenesis appears to play an important role in cervical cancer development and progression, therefore VEGF inhibition appears to be a rationale therapeutic strategy for cervical cancer. There is increasing evidence that combining an anti-angiogenic agent with either cytotoxic chemotherapy or radiation enhances anti-tumor activity. This study combines the current most active chemotheraputic regimen for cervical cancer (cisplatin + topotecan) with an anti-angiogenic agent.

Inclusion Criteria:

• Recurrent or persistent squamous, adenosquamous or adenocarcinoma of the uterine cervix not amenable to curative treatment with surgery and/or radiotherapy
• No prior therapy (radiation, chemotherapy, hormonal therapy or immunotherapy) for recurrence or persistence. May have received platinum in combination with radiation as part of up-front treatment or adjuvant treatment
• Must have measurable disease as defined by RECIST criteria
• Must have at least one "target lesion" to assess response
• Performance status of 0 or 1
• Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry
• At least 4 weeks must have elapsed since prior treatment
• Age >= 18 years
• Patients of childbearing potential must have a negative pregnancy test, use effective means of contraception
• Signed informed consent
• Bone marrow function: ANC >= 1500/ul; platelets >= 100,000 /ul
• Renal function: creatinine <= 1,5 X ULN (if > 1.5 creatinine clearance must be > 60 ml/min)
• Hepatic function: bilirubin <= 1.5 X ULN, AST and alkaline phosphatase <= 2.5 X ULN
• Neurologic function: neuropathy < CTC grade 1
• Coagulation: PT INR <= 1.5

Exclusion Criteria:

• Evidence of sepsis or severe infection
• Prior therapy for recurrence
• Patients with serious, non-healing wound, ulcer or bone fracture
• Patients with history or evidence of nervous system disease, including primary brain tumor, brain metastases, seizure not controlled with standard medical therapy, CVA, stroke, TIA or subarachnoid hemorrhage within 6 months of 1st date of treatment on study
• Patients with history of other invasive malignancy (treatment within last 5 years) other than non-melanoma skin cancer
• Patient with clinically significant cardiovascular disease defined as:
• Inadequately controlled hypertension (systolic > 150 and/or diastolic > 100 on antihypertensive medications); prior history of hypertensive crisis or hypertensive encephalopathy
• Unstable angina within 6 months of enrollment
• NYHA Grade II or greater congestive heart failure
• Serious cardiac arrythmia requiring medication
• Grade 2 or greater peripheral vascular disease; claudication within 6 months
• History of myocardial infarction within 6 months
• Previously diagnosed coagulopathy, disseminated intravascular coagulopathy, immune thrombocytopenia purpura, thrombotic thrombocytopenia purpura or tumor involving major vessels
• Significant vascular disease: aortic aneurysm, aortic dissection
• Active thromboembolic disease: pulmonary embolism, deep venous thrombosis
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 of study; anticipation of need for major surgical procedure during course of the study
• Minor surgical procedure other than central venous access placement, within 7 days prior to day 1 of study
• Patients with proteinuria - patients with urine protein of 1+ on dipstick or >=30 mg/dl at baseline should undergo UPCR; patients with UPCR of >=1.0 should be excluded
• Patients who are pregnant or lactating
• No prior investigational agent within 30 days or planned participation in an experimental drug study
• Patients whose circumstances do not permit completion of study or required follow-up
• Prior therapy with bevacizumab or topotecan. Prior platinum therapy allowed as part of initial treatment
• History of abdominal fistula, GI perforation or intra-abdominal abscess within 6 months prior to study enrollment.
• Known hypersensitivity to any component of bevacizumab

From the start of treatment through 30 days following the end of treatment.