A Pilot Study of Bevacizumab for Neoplastic Meningitis

Inclusion Criteria:

1. History of breast cancer, lung cancer or melanoma
2. Diagnosis of NM as proven either by: 1. positive CSF cytology, or 2. magnetic resonance neuro-imaging, or 3. both
3. Age \>/=18 years.
4. Routine laboratory studies adequate with bilirubin \</= 1.5 x upper limit of normal (ULN), AST \< 2.5 x ULN, creatinine \<1.0 x ULN, granulocytes \>1500, platelets\> 75,000; Hb \>/= 9.0.
5. Patient able to sign informed consent and willing to participate in study primary objectives
6. At least 1 week from last intrathecal chemotherapy (\>2 weeks if liposomal cytarabine). Patients are allowed to have received prior chemotherapy for their tumor. No limit on prior chemotherapies will be made. Patients who have been treated with tyrosine kinase inhibitors are permitted. Prior anti-VEGF targeted therapy is not permitted, unless patient has been off anti-VEGF therapy for 6 months and did not develop NM while on anti-VEGF therapy
7. Karnofsky performance status (KPS) \>/= 50%
8. Pre-treatment CSF Indium 111 CSF flow study without evidence of obstruction.
9. Patients on full-dose anticoagulants (e.g., warfarin) with PT international normalized ratio (INR) \>1.5 are eligible provided that: 1. Patients are receiving anticoagulation (warfarin or low molecular weight heparins (LMWH)) only if the patients can be off of warfarin for 4-5 days prior to the LP and placed on LMWH in that interim, and if the 'treatment dose' of LMWH can be safely held for 24 hours before and after the LP.
10. ( 9. continued) INR must be \<1.2 prior to LP in this circumstance. If patients are receiving thromboprophylaxis dose of LMWH, the patients can be enrolled, but the thromboprophylaxis LMWH must be able to be safely held for 12 hours prior to the LP. 2. The patient has no active bleeding or pathological condition that carries a high risk of bleeding 3. There is no evidence of serious or non-healing wound, ulcer or bone fracture
11. Ventricular reservoir NOT mandatory

Exclusion Criteria:

1. Evidence of active CNS hemorrhage in the brain or tumor lesions
2. Besides NM, other known CNS disease, except for treated brain metastases(Patients must be at least 1 month out from brain irradiation and have no evidence of progression or hemorrhage at that time, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period). Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery or a combination as deemed appropriate by the treating physician.
3. (2. continued) With respect to irradiation for other purpose (for NM or bone metastases, etc) patients need only 1 week out from the completion of irradiation. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
4. Patients with clinically significant cardiovascular disease are excluded 1) Inadequately controlled HTN (SBP \> 140 mmHg and/or diastolic blood pressure (DBP) \> 90 mmHg despite antihypertensive medication). 2) Prior history of hypertensive crisis or hypertensive encephalopathy. 3) New York Heart Association (NYHA) Grade II or greater congestive heart failure.
5. ( 4. Continued) 4) History of myocardial infarction or unstable angina within 6 months prior to Day 1. 5) History of stroke or transient ischemic attack within 6 months prior to Day 1. 6) Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1. 7) Clinically significant peripheral vascular disease. 8) Serious and inadequately controlled cardiac arrhythmia
6. History of hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
7. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
9. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1. Ventricular reservoir must have been placed more than 28 days prior to Day 1.
10. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
11. Serious, non-healing wound, active ulcer, or untreated bone fracture
12. Proteinuria as demonstrated by UPC ratio \>/=1.0 at screening or by urine dipstick \>/= 2+. (Patients discovered to have \>/= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \</= 1g of protein in 24 hours to be eligible).
13. Known hypersensitivity to any component of bevacizumab
14. Intrathoracic or extrathoracic lung carcinoma of squamous cell histology. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is acceptable.
15. (14. continued) Patients with extrathoracic-only squamous cell NSCLC are eligible. Patients with only peripheral lung lesions (of any non squamous NSCLC histology, except small cell histology) will also be eligible (a peripheral lesion is defined as a lesion in which the epicenter of the tumor is \</= 2 cm from the costal or diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung and is \>/= 2 cm from the trachea, main, and lobar bronchi).
16. Pregnant (positive pregnancy test) or nursing women. Angiogenesis is critical to fetal development and the inhibition of angiogenesis following administration of AVASTIN is likely to result in adverse effects on pregnancy. There are no adequate and well-controlled studies in pregnant women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 2 months after the completion of bevacizumab therapy.
17. General Medical Exclusions 1) Inability to comply with study and/or follow-up procedures 2) Life expectancy of less than 6 weeks 3) Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this Genentech supported study 4) Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within the last 5 years