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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00335959
• Other study ID #: CDR0000476577
• Secondary ID: U10CA032102S0425
• Status: Terminated
• Phase: Phase 2
• First received: June 8, 2006
• Last updated: July 12, 2012
• Start date: May 2006

Study information

• Verified date: July 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

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.
• oxaliplatin
130 mg/m2 by 2-hour infusion Days 1 and 22

Procedure:
• conventional surgery
Distal subtotal gastrectomy, total gastrectomy, or proximal 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.

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Shaw Regional Cancer Center	Edwards	Colorado
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Metro Health Hospital	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington
United States	Hackley Hospital	Muskegon	Michigan
United States	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Yes