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

This study has been terminated.
(Closed due to slow accrual)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00335959
First received: June 8, 2006
Last updated: July 12, 2012
Last verified: July 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
 Drug: capecitabine
Drug: oxaliplatin
Procedure: conventional surgery
Radiation: radiation therapy
 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Chemoradiation Therapy With Oxaliplatin and Capecitabine for Patients With Surgically Resectable Gastric Cancer: A Pilot Phase II Trial With Molecular Correlates

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Pathologic Complete Response [ Time Frame: 17-19 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events after pre-operative chemotherapy, after pre-operative chemoradiation and within 14 days of surgery. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 7
Study Start Date: May 2006
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy, Chemoradiation, Surgery

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
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.
Other Name: Xeloda (NSC-712807)
Drug: oxaliplatin
130 mg/m2 by 2-hour infusion Days 1 and 22
Other Name: Eloxatin (NSC-266046)
Procedure: conventional surgery
Distal subtotal gastrectomy, total gastrectomy, or proximal gastrectomy
Other Name: gastrectomy
Radiation: radiation therapy
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.
Other Name: RT

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00335959

  Show 75 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Lawrence P. Leichman, MD Desert Regional Medical Center Comprehensive Cancer Center
Study Chair: Syed A. Ahmad, MD Barrett Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00335959     History of Changes
Other Study ID Numbers: CDR0000476577, U10CA032102, S0425
Study First Received: June 8, 2006
Results First Received: July 12, 2012
Last Updated: July 12, 2012
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
adenocarcinoma of the stomach
stage I gastric cancer
stage II gastric cancer
stage III gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Capecitabine
 Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2012