Clinical trial NCT00335959: S0425 Oxaliplatin, Capecitabine, and RT in Treating Patients W/Stomach Cancer That Can Be Removed By Surgery
Official title: Neoadjuvant Chemoradiation Therapy With Oxaliplatin and Capecitabine for Patients With Surgically Resectable Gastric Cancer: A Pilot Phase II Trial With Molecular Correlates
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: adenocarcinoma of the stomach
stage I gastric cancer
stage II gastric cancer
stage III gastric cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-06-12
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: 17-19 weeks
Secondary outcomes:
measure: Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
timeFrame: Patients were assessed for adverse events after pre-operative chemotherapy, after pre-operative chemoradiation and within 14 days of surgery.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Palm Springs
country: United States
facility: Desert Regional Medical Center Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Edwards
country: United States
facility: Shaw Regional Cancer Center
state: Colorado
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Savannah
country: United States
facility: Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
state: Georgia
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grand Rapids
country: United States
facility: Metro Health Hospital
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Muskegon
country: United States
facility: Hackley Hospital
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Rochester
country: United States
facility: Interlakes Oncology/Hematology PC
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology
state: Washington
city: Mt. Vernon
country: United States
facility: Skagit Valley Hospital Cancer Care Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: Desert Regional Medical Center Comprehensive Cancer Center
name: Lawrence P. Leichman, MD
role: STUDY_CHAIR
affiliation: Barrett Cancer Center
name: Syed A. Ahmad, MD
role: STUDY_CHAIR
References: