An Open Label Study of AMG 706 in Subjects With Advanced Gastrointestinal Stromal Tumors (GISTs) Who Developed Progressive Disease or Relapsed While on Imatinib Mesylate

Study start date: October 1, 2004

Inclusion Criteria * Age ≥ 18 years; * Disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) during previous treatment with imatinib mesylate at least 600 mg daily for at least 8 weeks, as per two independently assessed prestudy computerized tomography (CT) scans; * Presence of at least one measurable (per RECIST) * Progressing tumor lesion not previously treated with radiotherapy or embolization and evaluable by CT scan or magnetic resonance imaging (MRI); * Karnofsky performance status ≥ 60; * imatinib treatment terminated at least 7 days before study day 1; * Adequate hepatic, renal, and cardiac function. Exclusion criteria: * Prior malignancy (other than GIST, in situ cervical cancer, or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years; cardiac disease including myocardial infarction, unstable angina, and congestive heart failure (New York Heart Association class \> II), * uncontrolled hypertension (systolic \> 145 mmHg or diastolic \> 85 mmHg), * History of arterial thrombosis or deep vein thrombosis (including pulmonary embolus) within 1 year of study day 1; * Absolute neutrophil count \< 1.5x109/L, platelet count \< 100x109/L, hemoglobin \< 9.0 g/dL; * Prior treatment with motesanib diphosphate or other KIT (except imatinib) or VEGF inhibitors. * The study was approved by the institutional review board of each participating institution, and all patients provided written informed consent before any study-related procedures were performed.