PTK787/ZK222584 in the Treatment of Metastatic Gastrointestinal Stromal Tumors Resistant to Imatinib

Inclusion Criteria:

* Patients with histologically confirmed GIST
* Imatinib resistance (primary resistance with progression, or progression after initial response). Resistance is defined as objective evidence of progression after at least 4 weeks of treatment with imatinib.
* Imatinib therapy has been interrupted \>7 days before study entry
* Metastatic disease confirmed histologically, cytologically or radiologically
* Presence of measurable tumor lesions as determined by RECIST criteria
* Age 18 years or older
* WHO performance status of 2 or less
* Blood neutrophil count (ANC) 1.5 x 10\^9/L or higher
* Platelet count 100 x 10\^9/L or higher
* Serum bilirubin 1.5 x ULN (upper limit of normal) or less
* Serum creatinine 2.0 x ULN or less
* Written informed consent obtained according to local guidelines

Exclusion Criteria:

* Patients who have received chemotherapy less than 4 weeks prior to entry into this study or who have not recovered from side effects of such therapy
* Patients who have received a cumulative dose of doxorubicin \>450 mg/m2 or epirubicin 800 mg/m2
* Patients who have received immunotherapy within 2 weeks or who have not recovered from side effects of such therapy
* Patients who have received radiotherapy within 2 weeks or who have not recovered from side effects of such therapy
* Major surgery within 2 weeks prior to entry into this study or patients who have not recovered from side effects of such therapy
* Patients who have received investigational drugs within 4 weeks prior to entry into this study or who have not recovered from side effects of such therapy
* Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control
* Concurrent severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months, poorly controlled hypertension, history of labile hypertension, history of poor compliance with antihypertensive regimen, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study
* Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
* Confirmed diagnosis of HIV infection
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK222584 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the capsules/tablets)
* Patients who are taking Coumadin (warfarin sodium); heparin is acceptable.
* Patients unwilling to, or unable to, comply with the protocol