Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer

This is an interventional treatment trial for Cervical Cancer Read More

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