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

Study Overview
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Brief Summary
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Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. This phase II trial is studying how well imatinib mesylate works in treating patients with refractory metastatic and/or unresectable stomach or gastroesophageal junction cancer.

Detailed Description
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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.

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

Conditions
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Recurrent Gastric Cancer, Stage IV Gastric Cancer

Intervention / Treatment
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* Drug: imatinib mesylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (imatinib mesylate)<br>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. | Drug: imatinib mesylate<br>* Given orally<br>* Other names: Glivec;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by X-Ray, MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Up to 6 years | 
| Toxicity Summary | Toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. Grade 3 and above adverse events possibly, probably or definitely related to treatment. | Up to 30 days post treatment | 
| Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 30 days post treatment | 
| Overall Survival | Will be summarized using the Kaplan-Meier product-limit estimators. | From first day of treatment to time of death due to any cause, assessed up to 5 years post-treatment | 
| Time to Treatment Failure | Defined as the time from start of treatment to the discontinuation of treatment for any reason, including disease progression, treatment toxicity, patient preference, or death Will be summarized using the Kaplan-Meier product-limit estimators. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | From first day of treatment until discontinuation of treatment, assessed up to 30 days post treatment | 
| Baseline Gene Expression Levels of the Target Genes (PDGF-R and PDGF), Genes Associated With Induction of Apoptosis (Bcl-2, Bax), and Cell Cycle Regulatory Genes (p53, p21, p27 | Will summarized overall and according to response and toxicity (if numbers permit), using medians, quartiles and ranges - or if a transformation is found to render the data compatible with the normal assumptions, with means, standard deviations, and confidence intervals. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously established cut-points) and constructing Kaplan-Meier plots. | Baseline |