The purpose of this study is to examine if PTK787/ZK222584 (vatalanib) will stabilize or decrease rising biochemical markers along with progressive disease or syndrome symptoms in patients with metastatic neuroendocrine tumors.

This is an open-label, phase II study evaluating the safety and efficacy of PTK787/ZK222584 administered daily in subjects with neuroendocrine tumors that are experiencing progressive disease and/or whose tumor-related syndrome symptoms (flushing and diarrhea) are considered inadequately controlled despite optimal doses of octreotide therapy. Inadequate control is defined as a minimum of 2 flushing episodes or 6 bowel movements per day for 7 consecutive days. Subjects who meet all inclusion and exclusion criteria and have completed all baseline and screening testing will receive an initial dose of PTK787/ZK222584 1,250 mg once daily and subjects will also remain on the scheduled doses of Sandostatin LAR 30 mg every 4 weeks. Both drugs will be dosed on a flat schedule of mg, not by weight or body surface area. The PTK787/ZK222584 medication will be taken orally with daily dosing. Each tablet of PTK787/ZK 222584 is 250 mg. The subject will take five tablets of study medication per day 2 tabs am and 3 tabs pm. Subjects may continue to receive therapy as long as they do not experience unacceptable toxicities or evidence of disease progression as defined by RECIST criteria. Subjects will be evaluated with a daily log to assess the degree of symptom control (flushing and diarrhea) and subjects will be monitored every 2 weeks for 3 months then monthly for biochemical control and every three months for tumor response. Subjects will be monitored by the Investigator every two weeks for 3 months then monthly for safety and efficacy.

Inclusion Criteria:

• Biopsy-proven metastatic neuroendocrine tumors (which extent is disease is determined by CT scan or MRI) and biochemical evidence of disease.
• Evidence of progressive disease or inadequate controlled disease related syndrome symptoms.
• Must be receiving Sandostatin LAR 30mg every 4 weeks
• Age >or= to 18 years old
• Karnofsky Performance Status > or = 60
• Measurable lesion(s) as per the modified RECIST criteria
• Laboratory values <or= 2 weeks prior to randomization: ANC >or= 1.5 x 10(9)/L, Platelets >or= 100 x 10 (9), Hemoglobin >or= 9g/dL, Serum creatinine <or= 1.5 ULN, Serum bilirubin <or= 1.5 ULN, Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <or= 3.0 x ULN (<or= 5 x ULN if liver metastases present), Negative for proteinuria based on dip stick reading OR documentation of 1+ result for protein on dip stick reading, then total urinary protein <or= 500mg and measured creatinine clearance >or= 50ml/min from a 24 hour urine collection.
• Life expectancy >or= 12 weeks.
• Written informed consent obtained according to local guidelines.

Exclusion Criteria:

• Had previous radiolabeled somatostatin analog therapy within the last 6 months.
• Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease)
• Undergone cryoablation of hepatic metastasis within the last 2 months.
• History or presence of central nervous system (CNS) disease (ie:primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
• History of another primary malignancy <or= 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin.
• Prior chemotherapy <or= 3 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities.
• Prior biologic or immunotherapy <or= 2 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities.
• Prior full field radiotherapy <or= 4 weeks or limited field radiotherapy <or= 2 weeks prior to randomization. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
• Major surgery (ie:laparotomy) <or= 4 weeks prior to randomization. Minor surgery <or= 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities.
• Patients who have received investigational drugs <or= 4 weeks prior to registration.
• Prior therapy with anti-VEGF agents
• Pleural effusion or ascites that causes respiratory compromise (>or= 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. Barrier contraceptives must be used throughout the trial in both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, therefore not considered effective for this study. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of study treatment.
• 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 \