An Open Label Phase II Study Evaluating the Safety and Efficacy of CPTK787/ZK222584 in Patients With Metastatic Neuroendocrine Tumors That Have Evidence of Progressive Disease or an Increase in Disease Related Syndrome Symptoms

Inclusion Criteria

Inclusion:

- Biopsy-proven metastatic neuroendocrine tumors and biochemical evidence of disease

- Evidence of progressive disease with measurable lesion(s) or inadequate controlled
disease syndrome.

- Receiving Sandostatin LAR 30 mg q 4 weeks

- Age equal to or greater than 18 years

- Karnofsky Performance Status equal to or greater than 60

- Lab values within 2 weeks prior to randomization:

- Absolute Neutrophil Count equal to or greater than 1.5 x 109/L

- Platelets equal to or greater than 100 x 109/L

- Hemoglobin equal to or greater than 9 g/dL

- Serum creatinine & bilirubin equal to or less than 1.5 ULN

- AST & ALT equal to or less than 3.0 x ULN equal to or less than 5 x ULN if liver
metastases present

- Negative for proteinuria based on dip stick reading OR, if documentation of +1
result for protein on dip stick reading, then total urinary protein equal to or
less than 500 mg and measured creatinine clearance equal to or greater than 50
mL/min from a 24-hour urine collection

- Life expectancy 12 weeks or more

- Written informed consent obtained according to local guidelines

Exclusion:

- Previous radiolabeled somatostatin analog therapy within 6 months

- Hepatic artery embolization within 6 months (1 month if there are other sites of
measurable disease)

- Cryoablation of hepatic metastasis within 2 months

- History or presence of CNS disease

- History of another primary malignancy equal to or less than 5 years, with the
exception of inactive basal or squamous cell carcinoma of the skin

- Prior chemotherapy within 3 weeks prior to randomization.

- Prior biologic or immunotherapy within 2 weeks prior to randomization.

- Prior full field radiotherapy or major surgery within 4 weeks or limited field
radiotherapy within 2 weeks prior to randomization.

- Must have recovered from all therapy-related toxicities.

- Minor surgery within 2 weeks prior to randomization.

- Any investigational drugs within 4 weeks prior to randomization

- Prior therapy with anti-VEGF agents

- Pleural effusion or ascites that causes respiratory compromise equal to or greater
than CTC grade 2 dyspnea

- Female patients who are pregnant or breast feeding or adults of reproductive
potential not employing an effective method of birth control. Women of childbearing
potential must have a negative serum pregnancy test 48 hours prior to study
treatment.

- Any of the following concurrent severe and/or uncontrolled medical conditions which
could compromise participation in the study:

- Uncontrolled high blood pressure, history of labile hypertension, or history of
poor compliance with an antihypertensive regimen

- Unstable angina pectoris

- Symptomatic congestive heart failure

- Myocardial infarction within 6 months prior to randomization

- Active or uncontrolled infection

- Interstitial pneumonia or extensive & symptomatic interstitial fibrosis of the
lung

- Chronic renal disease

- Subjects at risk of significant cardiac arrhythmias

- Uncontrolled diabetes

- Acute or chronic liver disease

- Impairment of gastrointestinal function or GI disease that may significantly
alter the absorption of PTK787/ZK 222584

- A confirmed diagnosis of human immunodeficiency virus infection are excluded at the
investigator's discretion

- If you are taking therapeutic warfarin sodium or similar oral anticoagulants. Heparin
is allowed.

- If you are unwilling to or unable to comply with the protocol

- If you have symptomatic gallstones

- If you have received glucocorticoid therapy within 6 months, or who are currently
receiving any chemotherapeutic agents, insulin sensitizers, or exogenous growth
hormones

- If you have unacceptable concomitant diagnoses, or who have received medication
and/or therapies that would place the patient at increase risk, or would in the
opinion of the investigator, interfere with the evaluation of efficacy and safety

- If you exhibit symptoms indicative of intolerance of Sandostatin LAR