The Safety and Efficacy of CPTK787/ZK222584 in Patients With Metastatic Neuroendocrine Tumors (CPTK787)

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