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.

Condition	Treatment or Intervention	Phase
gastrointestinal stromal tumor	Drug: imatinib mesylate  Drug: oblimersen  Procedure: antisense therapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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
• No symptomatic brain metastases

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 known hypersensitivity to phosphorothioate oligonucleotides
• No other concurrent significant medical disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

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

Surgery

• No prior organ allografts

Other

• Recovered from all prior therapy
• 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

Study chairs or principal investigators

Jonathan C. Trent, MD, PhD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000383199; MDA-2003-0761; NCI-6122; NCT00091078
Record last reviewed:  August 2004
Last Updated:  February 24, 2005
Record first received:  September 7, 2004
ClinicalTrials.gov Identifier:  NCT00091078
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08