Imatinib, Capecitabine, and Cisplatin in Treating Patients With Unresectable or Metastatic Stomach Cancer

Study Overview
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Brief Summary
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RATIONALE: Imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of imatinib when given together with capecitabine and cisplatin in treating patients with unresectable or metastatic stomach cancer.

Detailed Description
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OBJECTIVES: Primary To determine the maximum tolerable dose and assess the safety and tolerability of imatinib mesylate in combination with capecitabine and cisplatin in patients with unresectable or metastatic gastric cancer. Secondary To assess the preliminary antitumor activity of this regimen in these patients. To assess the response with regard to the expression and/or mutation of the tyrosine kinase receptors PDGF-R and c-kit in gastric cancer. OUTLINE: This is a dose-escalation study of imatinib mesylate. Patients receive oral imatinib mesylate once daily on days -4 to 21 in course 1 and on days 1-21 in all subsequent courses, oral capecitabine twice daily on days 1-14, and cisplatin IV on day 1. Courses repeat every 3 weeks* for 12 months in the absence of disease progression or unacceptable toxicity. NOTE: *First course is 25 days. After completion of study therapy, patients are followed every 3 weeks.

Official Title
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A Phase I Study of Capecitabine, Cisplatin and Imatinib in Patients With Unresectable or Metastatic Gastric Cancer.

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: cisplatin
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed gastric cancer Unresectable and/or metastatic disease Incurable with any conventional multimodality approach by interdisciplinary assessment of the local tumor board Immunohistochemical documentation of c-kit (CD117) and PDGF-R overexpression by tumor if obtainable (preferably on a tumor sample taken within 6 weeks of study entry) At least one evaluable site of disease according to RECIST criteria No known brain metastasis or CNS disorder that might alter study compliance or may worsen during or following therapy PATIENT CHARACTERISTICS: ECOG performance status 0-2 WBC ≥ 3,000/μL ANC ≥ 2,000/μL Platelet count ≥ 100,000/μL Hemoglobin ≥ 9.0 g/dL Total bilirubin < 2 times upper limit of normal (ULN) SGOT and SGPT < 2.5 times ULN (5 times ULN if hepatic metastases present) Glomerular filtration rate ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study treatment No known or documented hypersensitivity against fluoropyrimidines, tyrosine kinase inhibitors, cisplatin, other platinums, or their respective derivatives No gastrointestinal disorder that might affect the gastrointestinal absorption of capecitabine or imatinib mesylate or ability to swallow for the oral administration of capecitabine or imatinib mesylate At least 5 years since prior primary malignancy except if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or carcinoma in situ of the cervix No other concurrent malignant disease No NYHA class III-IV cardiac disease (i.e., congestive heart failure or myocardial infarction within the past 6 months) No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection) No known neuropathy, impaired hearing, history of seizures, and/or psychiatric disorder that might alter study compliance or may worsen during or following therapy No documented dihydropyrimidine dehydrogenase deficiency No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known diagnosis of HIV infection or other serious uncontrolled infections No significant history of non-compliance to medical regimens or inability to grant reliable informed consent PRIOR CONCURRENT THERAPY: No chemotherapy or investigational agents within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C) unless the disease is rapidly progressing No prior radiotherapy to ≥ 25% of the bone marrow No major surgery within the past 2 weeks No concurrent warfarin or acetaminophen Therapeutic anticoagulation using heparin or low-molecular weight heparin allowed No concurrent sorivudine or related substances No other concurrent anticancer agents, including chemotherapy and biologic agents No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 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: Imatinib mesylate<br>Imatinib mesylate 300mg/day(maximum dose will be 800 mg) on day -4, -3, -2, -1, 1, 2, 3 through d21 in combination with capecitabine 1250 mg/m2 twice daily (d1-d14) and iv cisplatin 60mg/m2 | Drug: capecitabine<br> <br> Drug: cisplatin<br> <br> Drug: imatinib mesylate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| Tolerability |  |  | 
| Overall tumor response as assessed by RECIST |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression of disease |  |  | 
| Overall survival |  |  | 
| Quality of life |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III gastric cancer, stage IV gastric cancer