Bevacizumab and Paclitaxel for Neuroendocrine Tumors of the Cervix

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)