Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer
Condition: Cervical Cancer
MeSH terms: Uterine Cervical Neoplasms
Intervention: Topotecan; Cisplatin; Bevacizumab
Intervention MeSH terms: Bevacizumab; Topotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility 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