Bevacizumab and Paclitaxel for Neuroendocrine Tumors of the Cervix
Condition: Cervical Cancer; Uterine Cancer
MeSH terms: Uterine Cervical Neoplasms; Neuroendocrine Tumors; Uterine Neoplasms
Intervention: Bevacizumab; Paclitaxel
Intervention description: 10 mg/kg IV twice weekly on days 1 and 15.; 60 mg/m^2 IV weekly on days 1, 8, 15, and 22.
Intervention MeSH terms: Paclitaxel; Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Female
Healthy volunteers: No
Keywords: Cervical Cancer; Uterine Cancer; Bevacizumab; Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF; Paclitaxel; Taxol

Summary:

      Objectives:

      Primary:

      To estimate the efficacy of bevacizumab and paclitaxel in patients with recurrent small cell,
      large cell, and neuroendocrine cervical and uterine cancers, as measured by progression-free
      survival.

      Secondary:

        1. To estimate the efficacy of bevacizumab and paclitaxel in patients with recurrent small
           cell, large cell, and neuroendocrine cervical and uterine cancers, as measured by
           overall survival.

        2. To determine the response rates in patients with recurrent small cell, large cell, and
           neuroendocrine cervical and uterine cancers when treated with bevacizumab and
           paclitaxel.

        3. To characterize the quality of life (QoL) in patients with recurrent small cell, large
           cell, and neuroendocrine cervical and uterine cancers when treated with bevacizumab and
           paclitaxel.

        4. To determine the nature and degree of toxicity in patients with advanced or recurrent
           small cell, large cell, or neuroendocrine cervical and uterine cancers when treated with
           bevacizumab and paclitaxel.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologically confirmed, advanced stage (stage IVB), recurrent, or
             persistent small cell, large cell, or neuroendocrine tumor of the uterine corpus and
             cervix

          2. All patients must have measurable disease. Measurable disease is defined as at least
             one lesion that can be accurately measured in at least one dimension (longest
             dimension to be recorded). Each lesion must be > / = 20 mm when measured by
             conventional techniques, including palpation, plain x-ray, CT, and MRI, or > / = 10 mm
             when measured by spiral CT. Biopsy confirmation is required if the lesion measures <
             30 mm or if the treating physician determines it is clinically indicated.

          3. Patients must have at least one "target lesion" to be used to assess response on this
             protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Tumors
             within a previously irradiated field will be designated as "non-target" lesions unless
             progression is documented or a biopsy is obtained to confirm persistence at least 90
             days following completion of radiation therapy.

          4. Patients must have adequate: BONE MARROW FUNCTION: Absolute neutrophil count (ANC)
             greater than or equal to 1,500/mcl and platelets greater than or equal to 100,000/mcl.
             RENAL FUNCTION: Creatinine less than or equal to 1.5 * institutional upper limit
             normal (ULN), and measured or estimated creatinine clearance greater than or equal to
             50 ml/min. For the purpose of estimating the creatinine clearance, the formula of
             Jelliffe should be utilized. HEPATIC FUNCTION: Bilirubin less than or equal to 1.5 *
             ULN. serum glutamate oxaloacetate transaminase (SGOT) and alkaline phosphatase less
             than or equal to 2.5 * ULN

          5. Patients must have adequate: BLOOD COAGULATION PARAMETERS: prothrombin time (PT) such
             that international normalized ratio (INR) is < / = 1.5 (or an in-range INR, usually
             between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a
             partial thromboplastin time (PTT) < 1.2 times the upper limit of normal. NEUROLOGIC
             FUNCTION: Neuropathy (sensory and motor) less than or equal to [1] Common Toxicity
             Criteria for Adverse Effects (CTCAE) grade 1.

          6. Patients must have signed an approved informed consent and authorization permitting
             release of personal health information.

          7. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Grade of 0 or 1

          8. Patients must be free of clinically significant infection.

        Exclusion Criteria:

          1. Patients who have progressed through or recurred within 3 months of treatment with a
             taxane agent administered on a weekly basis.

          2. Patients who have previously been treated with bevacizumab or other anti-angiogenic
             agents

          3. Patients who are less than 4 weeks from prior chemotherapy and/or radiation therapy

          4. Patients with ECOG Performance Grade of 2, 3 or 4

          5. Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
             being present within the last 5 years. Patients are also excluded if their previous
             cancer treatment contraindicates this protocol therapy

          6. Subjects meeting any of the following criteria are ineligible for study entry: (a)
             Inability to comply with study and/or follow-up procedures (b) Current, recent (within
             4 weeks of the first infusion of this study), or planned participation in an
             experimental drug study other than a Genentech-sponsored bevacizumab cancer study

          7. Inadequately controlled hypertension (defined as systolic blood pressure >140 or
             diastolic blood pressure > 90 mmHg on antihypertensive medications)

          8. Any prior history of hypertensive crisis or hypertensive encephalopathy

          9. New York Heart Association (NYHA) Grade II or greater congestive heart failure

         10. History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

         11. History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

         12. Known metastatic cervical cancer to the central nervous system

         13. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

         14. Symptomatic peripheral vascular disease

         15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

         16. Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

         17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

         18. Serious, non-healing wound, ulcer, or bone fracture

         19. Proteinuria at screening as demonstrated by urine dipstick for proteinuria > / = 2+
             (patients discovered to have > / = 2+ proteinuria on dipstick urinalysis at baseline
             should undergo a 24 hour urine collection and must demonstrate < / = 1g of protein in
             24 hours to be eligible)

         20. Known hypersensitivity to any component of bevacizumab

         21. Pregnant (positive pregnancy test) or lactating

         22. Patients receiving black cohosh, dong quai, valerian, St. John's wort, kava kava, gotu
             kola. Patient cannot have received these medications within 14 days of therapy start.

         23. Patients with a known hypersensitivity to taxanes, Cremophor EL (polyoxyethylated
             castor oil), or any component of the formulation.

         24. History of hemoptysis (>/= ½ teaspoon of bright red blood per episode) within 1 month
             prior to Day 1

         25. Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)