SU011248 in Treating Patients With Malignant Gastrointestinal Stromal Tumor

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant gastrointestinal stromal tumor
• Not amenable to surgery, radiotherapy, or combined modality therapy with curative intent

• Imatinib mesylate-resistant or -intolerant disease (last dose administered ≥ 2 weeks ago)

  • Failed prior imatinib mesylate therapy, defined by disease progression during treatment OR significant toxicity during treatment that precludes further treatment

    • Must have radiological confirmation of disease progression

  • Intolerance to prior imatinib mesylate, defined by 1 of the following:

    • Life-threatening adverse events at any dose (attempt to dose reduce or rechallenge not required)
    • Unacceptable toxicity induced by a moderate dose (e.g., 400 mg/day), specifically grade 3 toxicity OR grade 2 toxicity that is unacceptable to the patient (e.g., nausea) that persists despite standard countermeasures

• Unidimensionally measurable disease

  • At least 1 tumor mass ≥ 20 mm by conventional radiographic techniques or MRI OR ≥ 10-16 mm by spiral CT scan

    • Tumor evaluation by positron-emission tomography scan or ultrasound may not substitute for MRI or CT scan

  • The following are considered non-measurable disease:

    • Bone lesions
    • Ascites
    • Peritoneal carcinomatosis or miliary lesions
    • Pleural or pericardial effusions
    • Lymphangitis of the skin or lung
    • Cystic lesions
    • Irradiated lesions
    • Disease documented by indirect evidence only (e.g., laboratory tests, such as alkaline phosphatase)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm ^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• PT and PTT ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (5 times ULN for abnormalities due to underlying malignancy)
• Bilirubin ≤ 1.5 times ULN
• Albumin ≥ 3.0 g/dL

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• LVEF > lower limit of normal by MUGA scan
• Cardiac troponin T AND/OR cardiac troponin I ≤ ULN
• No ongoing cardiac dysrhythmias ≥ grade 2
• No atrial fibrillation of any grade
• No prolongation of the QTc interval to > 450 msec for males or > 470 msec for females

• None of the following conditions within the past 12 months:

  • Myocardial infarction
  • Severe or unstable angina
  • Symptomatic congestive heart failure
  • Cerebrovascular accident
  • Transient ischemic attack
  • Deep vein thrombosis
  • Other thromboembolic event

Pulmonary

• No pulmonary embolism within the past 12 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after study participation
• Amylase and lipase ≤ 1.0 times ULN
• Adrenocorticotrophic hormone (ACTH) stimulation test normal
• HIV negative
• No AIDS-related illness
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No immunotherapy since last dose of imatinib mesylate
• No concurrent biological response modifiers
• No concurrent immunotherapy

Chemotherapy

• No chemotherapy or chemoembolization therapy since last dose of imatinib mesylate
• No concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy to areas of measurable disease where progression has occurred in patients with imatinib mesylate-resistant disease

• No concurrent radiotherapy to the sole site of measurable disease

  • Concurrent palliative radiotherapy allowed provided no measurable lesions (target lesions) are included in the irradiated field

Surgery

• More than 12 months since prior coronary/peripheral artery bypass graft
• No prior surgery or cryotherapy on areas of measurable disease where progression has occurred in patients with imatinib mesylate-resistant disease
• No concurrent surgery to the sole site of measurable disease

Other

• Recovered from all prior therapy
• No investigational anticancer agent since last dose of imatinib mesylate
• No concurrent participation in another clinical trial
• No other concurrent anticancer therapy
• No other concurrent investigational drugs