Study of AMG 706 in Subjects With Advanced Gastrointestinal Stromal Tumors (GISTs)

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.