• Survival as measured by computed tomography every 2 months [ Designated as safety issue: No ]
• Progression-free survival as measured by follow up physical exam [ Designated as safety issue: No ]

• Survival as measured by computed tomography every 2 months
• Progression-free survival as measured by follow up physical exam

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Oblimersen may help imatinib mesylate kill more tumor cells by making tumor cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with oblimersen works in treating patients with advanced gastrointestinal stromal tumor that cannot be removed by surgery.

OBJECTIVES:

• Determine the efficacy of oblimersen and imatinib mesylate in patients with advanced unresectable gastrointestinal stromal tumors that progressed after prior imatinib mesylate.
• Determine the safety of this regimen in these patients.
• Correlate expression of bcl-2 with survival, time to progression, and response rate in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to extent of disease progression (limited vs generalized).

Patients receive oblimersen IV continuously on days 1-14. Patients also receive oral imatinib mesylate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 96 patients (48 per stratum) will be accrued for this study.

• Biological: oblimersen sodium
• Drug: imatinib mesylate

DISEASE CHARACTERISTICS:

• Histologically confirmed gastrointestinal stromal tumor

  • Advanced disease, defined as unresectable mestastatic or primary disease
• Kit-expressing tumor

• Limited* or generalized** disease progression after adequate therapy with imatinib mesylate (≥ 400 mg/day for at least 6 weeks), as defined by both of the following:

  • Increase in unidimensional tumor size of ≥ 10% AND did not meet criteria for partial response by CT scan density
  • Any new lesions, including new tumor nodules in a previous cystic tumor NOTE: *Some, but not all, tumor foci progressing AND not amenable to local therapy

NOTE: **Widespread progression of all tumor foci

• Measurable disease by CT scan

  • If a targeted lesion has been previously embolized or irradiated, there must be objective evidence of disease progression

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• PT and PTT ≤ 1.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• No uncontrolled chronic liver disease

Renal

• Creatinine ≤ 1.5 times ULN
• No uncontrolled chronic renal disease

Cardiovascular

• No New York Heart Association class III or IV cardiac disease
• No congestive heart failure
• No acute myocardial infarction within the past 2 months

Other

• Intellectually, emotionally, and physically able to maintain an ambulatory infusion pump
• No uncontrolled diabetes
• No uncontrolled seizure disorder
• No active uncontrolled infection
• HIV negative
• 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 concurrent significant medical disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior biologic therapy

Chemotherapy

• At least 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• No prior organ allografts

Other

• Recovered from all prior therapy such that severity is ≤ grade 1 for nonhematological toxicities except nausea and vomiting controlled with standard anti-emetic regimens, alopecia, fatigue, and peripheral edema
• At least 4 weeks since prior embolization
• At least 4 weeks since prior imatinib mesylate
• At least 4 weeks since other prior therapy

• No concurrent warfarin

  • Low-dose warfarin or low molecular weight heparin allowed for prophylaxis