Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborators: Genentech, Inc.; GlaxoSmithKline
• Treatments: Bevacizumab; Cisplatin; Topotecan

Criteria

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