S0425 Oxaliplatin, Capecitabine, and RT in Treating Patients W/Stomach Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with radiation therapy works in treating patients with stomach cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Determine the pathologic complete response rate in patients with primary gastric adenocarcinoma treated with neoadjuvant chemoradiotherapy comprising oxaliplatin, capecitabine, and radiotherapy. (This will not be completed as this study was closed early due to poor accrual.) Assess the frequency and severity of toxicities associated with this regimen. Explore, preliminarily, the association between DNA repair genes (ERCC-1, XRCC1, GST-P1, XPD, XPA, ribonucleotide reductase), target enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase, thymidine phosphorylase [TP]), and angiogenic factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], PD-ECGF, basic fibroblast growth factor, TSP-1 and -2, transforming growth factor [TGF]-β, and IL-8) and response to neoadjuvant therapy in patients with adenocarcinoma of the stomach. (This will not be completed as this study was closed early due to poor accrual.) Explore, preliminarily, the association of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response and toxicity to neoadjuvant chemoradiation therapy in these patients. (This will not be completed as this study was closed early due to poor accrual.) Explore, preliminarily, the feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response to neoadjuvant chemoradiation therapy. (This will not be completed as this study was closed early due to poor accrual.) OUTLINE: This is a multicenter, pilot study. Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1 and 22 and oral capecitabine twice daily on days 1-14 and 22-35 in the absence of disease progression or unacceptable toxicity. Neoadjuvant chemoradiotherapy: Patients receive oral capecitabine twice daily on days 43-77 and undergo radiotherapy once daily on days 43-47, 50-54, 57-61, 64-68, and 71-75 in the absence of disease progression or unacceptable toxicity. Surgery: Patients with stable or responding disease undergo surgery 4-6 weeks after completion of chemoradiotherapy. Tumor tissue is obtained at surgery or endoscopic biopsy. Gene expression analysis and comparative genomic hybridization testing are conducted on the tissue. Blood is drawn prior to beginning study treatment and is analyzed for germline polymorphisms. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Official Title
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Neoadjuvant Chemoradiation Therapy With Oxaliplatin and Capecitabine for Patients With Surgically Resectable Gastric Cancer: A Pilot Phase II Trial With Molecular Correlates

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: oxaliplatin
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary adenocarcinoma of the stomach, meeting the following criteria: Newly diagnosed disease amenable to curative resection Stage IB-III (T2-4) Measurable or nonmeasurable disease Enlarged lymph nodes outside of radiation fields must have preoperative biopsies No positive lymph nodes outside of radiation fields No distant metastasis No gastroesophageal junction tumors PATIENT CHARACTERISTICS: Zubrod performance status 0-1 Absolute neutrophil count ≥ 1,500/mm³ WBC ≥ 3,000/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 times upper limit of normal Albumin ≥ 3 g/dL Bilirubin normal No evidence of ischemic heart disease by EKG No coronary artery disease requiring active medical treatment No symptoms of angina No history of myocardial infarction No deep vein thrombosis within the past 12 months No pre-existing peripheral neuropathy No active pneumonia or inflammatory lung infiltrate No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for ≥ 5 years No clinically significant comorbid medical conditions that would prevent delivery of chemotherapy, radiotherapy, or the performance of surgery Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: At least 4 weeks since prior and no concurrent sorivudine or brivudine No prior therapy for this malignancy, including chemotherapy, surgery, immunotherapy, or radiotherapy No prior coronary angioplasty or stenting No concurrent 2-dimensional or intensity-modulated radiotherapy

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: Chemotherapy, Chemoradiation, Surgery<br>Chemotherapy: Oxaliplatin, 130 mg/m2, 2 hour IV infusion on Days 1 and 22; Capecitabine 850 mg/m2/dose, PO q 12 hours on Days 1-14 and 22-35 Chemoradiation: Capecitabine 650 mg/m2/dose, PO q 12 hours on days 43-77; Radiation therapy 180 cGy/day, 5 days/week beginning on Day 43. Surgery: Distal subtotal gastrectomy, total gastrectomy, or proximal gastrectomy | Drug: capecitabine<br>* 850 mg/m2/dose PO q 12 hours Days 1-14 and 22-35. 650 mg/m2/dose PO q 12 hours Days 43-77.<br>* Other names: Xeloda (NSC-712807);Drug: oxaliplatin<br>* 130 mg/m2 by 2-hour infusion Days 1 and 22<br>* Other names: Eloxatin (NSC-266046);Procedure: conventional surgery<br>* Distal subtotal gastrectomy, total gastrectomy, or proximal gastrectomy<br>* Other names: gastrectomy;Radiation: radiation therapy<br>* Beginning Day 43, patients will be treated 5 days/week at 180 cGy/day times 25 fractions to a total dose of 4,500 cGy.<br>* Other names: RT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response | Pathologic complete response rates (pCR) of primary gastric adenocarcinoma when treated with oxaliplatin and capecitabine followed by capecitabine and radiation pre-operatively. On review of the resected gastric specimen and accompanying lymph nodes, pCR is no cancer recognized by the pathologist. Margins are free of tumor. | 17-19 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal. | Patients were assessed for adverse events after pre-operative chemotherapy, after pre-operative chemoradiation and within 14 days of surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the stomach, stage I gastric cancer, stage II gastric cancer, stage III gastric cancer