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

SWOG Cancer Research Network

Status and phase: Terminated; Phase 2

Conditions: Gastric Cancer

Treatments: Drug: capecitabine; Procedure: conventional surgery; Radiation: radiation therapy; Drug: oxaliplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00335959

CDR0000476577

S0425 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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7 participants in 1 patient group

Chemotherapy, Chemoradiation, Surgery

Experimental group

Description:

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

Treatment:

Drug: oxaliplatin

Radiation: radiation therapy

Procedure: conventional surgery

Drug: capecitabine