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

Phase 2

Completed

• Conditions: Recurrent Gastric Cancer; Stage IV Gastric Cancer
• Interventions: Drug: imatinib mesylate; Other: laboratory biomarker analysis

• Registration Number: NCT00068380
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2003-09-10
• Study First Submitted QC: 2003-09-10
• Study First Posted: 2003-09-11
• Study Start: 2004-03
• Primary Completion: 2010-03
• Study Completion: 2010-03
• Results First Submitted: 2014-07-21
• Results First Submitted QC: 2014-07-21
• Results First Posted: 2014-08-12
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-15
• Last Update Posted: 2018-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (imatinib mesylate)	imatinib mesylate	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.
Treatment (imatinib mesylate)	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
Response Rate	Up to 6 years	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
Toxicity Summary	Up to 30 days post treatment	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.
Overall Survival	From first day of treatment to time of death due to any cause, assessed up to 5 years post-treatment	Will be summarized using the Kaplan-Meier product-limit estimators.
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	Baseline	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.
Time to Treatment Failure	From first day of treatment until discontinuation of treatment, assessed up to 30 days post treatment	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
Progression-free Survival	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	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.

Trial Locations

Locations (1)

City of Hope; 🇺🇸 Duarte, California, United States