A Phase III Randomized Study of Imatinib, With or Without Bevacizumab (NSC-704865), in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors

Inclusion Criteria

Criteria:

- Histologically confirmed gastrointestinal stromal tumor (GIST)

- Metastatic or unresectable disease

- Determined to be unresectable for cure

- Measurable and/or nonmeasurable disease by MRI or CT scan

- No known brain metastasis

- Zubrod performance status 0-3

- Platelet count >= 100,000/mm^3

- Absolute neutrophil count >=1,000/mm^3

- Hemoglobin >= 9 g/dL (transfusion allowed)

- Bilirubin =< 2.0 times upper limit of normal (ULN)

- SGOT/SGPT =< 2.5 times ULN (5 times ULN with liver involvement)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for up to 6
months after completion of study treatment

- No cerebrovascular accident, transient ischemic attack, myocardial infarction, or
unstable angina within the past 6 months

- No serious cardiac arrhythmia requiring medication

- No New York Heart Association class II-IV congestive heart failure

- No clinically significant peripheral vascular disease

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No contraindication to oral medications (e.g., severe dysphagia)

- G- or J-tubes allowed

- No history of hypertension unless well controlled (i.e., blood pressure < 160/90 mm
Hg) and on a stable regimen of antihypertensive therapy

- No serious nonhealing wound, ulcer, or bone fracture

- No other prior malignancy except for any of the following: adequately treated basal
cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage
I or II cancer that is currently in complete remission; any other cancer for which
the patient has been disease free for >= 5 years

- No significant traumatic injury in the past 28 days

- Recovered from prior therapy

- At least 28 days since prior chemotherapy

- At least 28 days since prior radiotherapy

- Evidence of progressive disease within the radiation field or disease outside the
radiation field

- No prior bevacizumab or other agents targeting vascular endothelial growth factor
(VEGF), VEGF receptor, or platelet-derived growth factor receptor (PDGFR) for
advanced disease

- These agents may have been used in the adjuvant setting provided no recurrence for >=
12 months after completion of therapy

- More than 28 days since prior major surgery or open biopsy

- No anticipated need for major surgery

- More than 7 days since prior fine-needle aspiration or core biopsies

- More than 7 days since prior procedure to place a portacath

- No other concurrent anticancer biologic agents, chemotherapy, radiotherapy, or any
other anticancer agents

- No concurrent therapeutic warfarin for anticoagulation

- Concurrent low-molecular weight heparin or other agents for therapeutic
anticoagulation or mini-dose warfarin for prophylaxis allowed

- No other concurrent investigational agents

- Creatinine =< 1.5 times ULN

- Urine protein:creatinine ratio < 1

- INR =< 1.5

- PTT normal