A Phase II Trial of STI571 in the Treatment of Metastatic Gastric Cancer

PRIMARY OBJECTIVES:

I. To determine the response rate, time to tumor progression, and overall survival in
patients with metastatic gastric cancer treated with STI571 who have failed one chemotherapy
regimen for metastatic disease.

II. To assess the toxicities of STI571 in these patients. III. To obtain preliminary data on
molecular correlates to determine clinical efficacy and toxicity.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk
[chemonaïve] vs poor risk [1 prior chemotherapy regimen]).

Patients receive oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4
weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 1-1.5
years.

Inclusion Criteria:

- Patients with metastatic and/or unresectable carcinoma of the stomach, who have
measurable disease

- Life expectancy > 3 months

- Karnofsky Performance Status > 60%

- Absence of an active infection

- Granulocyte count of > 1,500/mm^3

- Hemoglobin (Hgb) >= 9 mg/dl

- Serum bilirubin =< 1.5 mg/dl, regardless of liver involvement secondary to tumor

- Platelets > 100,000/mm^3

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
transaminase (SGPT) < 2.5 x the institutional upper limit of normal

- Calculated creatinine clearance of > 60 ml/min

- Patients must have signed written informed consent

- Female patients of child-bearing potential must have a negative blood or urine
pregnancy test within two weeks prior to initial study treatment

- Patients who have had prior chemotherapy or radiation therapy must have recovered from
any toxicities prior to study entry

- Patients must have radiographic imaging to document measurable disease within 28 days
prior to initial study therapy

Exclusion Criteria:

- Diagnosis of resectable carcinoma of the stomach

- Major surgery within four weeks of study entry

- Brain metastasis or known seizure disorder

- Fertile men and women not using an acceptable method of contraception

- Pregnant or lactating patients are excluded since STI571 may be harmful to the
developing fetus and child

- Patients known to be HIV positive and receiving HAART are excluded because of possibly
pharmacological interactions

- Active peptic ulceration or active gastrointestinal bleeding or any active bleeding
disorders

- Use of therapeutic doses of coumadin (warfarin) as anticoagulation

- Medical, social, or psychological factors which would prevent the patient from
completing the treatment protocol

- Patients with serious intercurrent illness which would preclude tolerance and
completion of the protocol treatment