S0356 Oxaliplatin, 5-FU, Radiation Therapy (RT), Surgery for Pts With Stage II or III Cancer of Esophagus or Gastroesophageal (GE) Junction

NCT ID: NCT00086996

Last Updated: 2013-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2011-08-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Oxaliplatin and fluorouracil may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy and radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin together with fluorouracil and radiation therapy works in treating patients who are undergoing surgery for stage II or stage III cancer of the esophagus or gastroesophageal junction.

Detailed Description

OBJECTIVES:

Primary

• Determine the pathologic complete response probability in patients with stage II or III adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant oxaliplatin, fluorouracil, and radiotherapy followed by definitive surgical resection.

Secondary

• Determine the frequency and severity of toxic effects associated with this neoadjuvant regimen in these patients.
• Determine the overall survival and progression-free survival of patients treated with this regimen.

Exploratory Analyses (subject to funding availability)

• Correlate, preliminarily, initial messenger ribonucleic acid (mRNA) levels of the genes for thymidylate synthase (TS), γ-glutamyl transpeptidase (γGT), γ-glutamyl cysteine (γ-GCS), DNA excision repair cross-complementing (ERCC-1), and xeroderma pigmentosum (XPA) with response and survival of patients treated with this regimen.
• Correlate, preliminarily, the mRNA levels of TS, γGT, γ-GCS, ERCC-1, and XPA before and after treatment with this regimen with survival of these patients.
• Correlate, preliminarily, specific genetic polymorphisms of TS and ERCC-1 with tumor response and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil (5-FU) IV continuously on days 8-43. Beginning on day 8, patients also undergo radiotherapy once daily, 5 days a week, for 5 weeks.
• Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks after completion of chemoradiotherapy.
• Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive chemotherapy comprising oxaliplatin IV over 2 hours on days 1, 15, and 29 and 5-FU IV continuously on days 1-36.

Treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 45-85 patients will be accrued for this study within 17-21 months.

Conditions

Esophageal Cancer

Keywords

adenocarcinoma of the esophagus; stage II esophageal cancer; stage III esophageal cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemo Plus RT, Surgery, Chemo

neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin

Group Type: EXPERIMENTAL

fluorouracil

Intervention Type: DRUG

Before surgery: 180 mg/m2/day by 24-hour infusion days 8 through 43. After surgery:180 mg/m2/day by 24-hour infusion days 1 through 36.

oxaliplatin

Intervention Type: DRUG

Before surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29. After surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29.

conventional surgery

Intervention Type: PROCEDURE

The surgical technique will depend upon the location and extent of tumor and individual surgeon preference.

radiation therapy

Intervention Type: RADIATION

Starting Day 8, patients will be treated 5 days/week at 180 centigray (cGy)/day times 25 fractions to a total dose of 4,500 cGy.

Interventions

fluorouracil

Before surgery: 180 mg/m2/day by 24-hour infusion days 8 through 43. After surgery:180 mg/m2/day by 24-hour infusion days 1 through 36.

Intervention Type: DRUG

oxaliplatin

Before surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29. After surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29.

Intervention Type: DRUG

conventional surgery

The surgical technique will depend upon the location and extent of tumor and individual surgeon preference.

Intervention Type: PROCEDURE

radiation therapy

Starting Day 8, patients will be treated 5 days/week at 180 centigray (cGy)/day times 25 fractions to a total dose of 4,500 cGy.

Intervention Type: RADIATION

Other Intervention Names

5-FU; eloxatin

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary adenocarcinoma of the thoracic esophagus or gastroesophageal junction

• No recurrent disease
• Primary esophageal tumor at least 20 cm below the incisors (if < 26 cm below the incisors, a bronchoscopy must be performed and cytology must be negative)
• Esophageal disease confined to esophagus and peri-esophageal soft tissue
• Gastroesophageal junction disease extending ≤ 2 cm into the gastric cardia
• Clinical stage II or III disease by CT scan or MRI

• If no esophageal mass is detected by these methods, esophageal endoscopic ultrasound is required to determine stage
• Positron-emission tomography scan is required to confirm stage
• Measurable or non-measurable disease by x-ray, scanning, or physical examination
• No celiac axis nodes ≥ 1.5 cm

• Measurable regional lymph nodes ≥ 1.5 cm at stations 2-10=N1 OR subdiaphragmatic lymph nodes at stations 15-19 ≤ 1.5 cm by CT scan or MRI allowed
• Palpable supraclavicular lymph nodes must be free of metastatic esophageal cancer by biopsy

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• White blood cell (WBC) count ≥ 3,000/mm^3
• Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

• Albumin ≥ 3 g/dL
• Bilirubin normal

Renal

• Creatinine ≤ 1.5 times upper limit of normal

Cardiovascular

• No myocardial infarction or cerebrovascular event within the past 6 months

Pulmonary

• No active pneumonia or inflammatory lung infiltrate

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No peripheral neuropathy ≥ grade 2
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for esophageal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for esophageal cancer
• No concurrent intensity-modulated radiotherapy

Surgery

• No prior surgical resection or attempted surgical resection of esophageal cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lawrence P. Leichman, MD

Role: STUDY_CHAIR

Desert Regional Medical Center Comprehensive Cancer Center

Charles R. Thomas, MD

Role: STUDY_CHAIR

OHSU Knight Cancer Institute

Locations

Mobile Infirmary Medical Center

Mobile, Alabama, United States

Providence Cancer Center

Anchorage, Alaska, United States

Highlands Oncology Group - Springdale

Bentonville, Arkansas, United States

East Bay Radiation Oncology Center

Castro Valley, California, United States

Eden Medical Center

Castro Valley, California, United States

Valley Medical Oncology Consultants - Castro Valley

Castro Valley, California, United States

Valley Medical Oncology

Fremont, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Highland General Hospital

Oakland, California, United States

Alta Bates Summit Medical Center - Summit Campus

Oakland, California, United States

Bay Area Breast Surgeons, Incorporated

Oakland, California, United States

CCOP - Bay Area Tumor Institute

Oakland, California, United States

Larry G Strieff MD Medical Corporation

Oakland, California, United States

Tom K Lee, Incorporated

Oakland, California, United States

Desert Regional Medical Center Comprehensive Cancer Center

Palm Springs, California, United States

Valley Care Medical Center

Pleasanton, California, United States

Valley Medical Oncology Consultants - Pleasanton

Pleasanton, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

Doctors Medical Center - San Pablo Campus

San Pablo, California, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Saint Anthony's Hospital at Saint Anthony's Health Center

Alton, Illinois, United States

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Good Samaritan Regional Health Center

Mount Vernon, Illinois, United States

Regional Cancer Center at Memorial Medical Center

Springfield, Illinois, United States

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Reid Hospital & Health Care Services

Richmond, Indiana, United States

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Southwest Medical Center

Liberal, Kansas, United States

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Olathe Cancer Center

Olathe, Kansas, United States

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Cotton-O'Neil Cancer Center

Topeka, Kansas, United States

St. Francis Comprehensive Cancer Center

Topeka, Kansas, United States

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, United States

Associates in Womens Health, PA - North Review

Wichita, Kansas, United States

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

CCOP - Wichita

Wichita, Kansas, United States

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Wesley Medical Center

Wichita, Kansas, United States

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Boston University Cancer Research Center

Boston, Massachusetts, United States

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States

Mecosta County Medical Center

Big Rapids, Michigan, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 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

Holland Community Hospital

Holland, Michigan, United States

Hackley Hospital

Muskegon, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital

Gape Girardeau, Missouri, United States

St. John's Regional Medical Center

Joplin, Missouri, United States

CCOP - Kansas City

Kansas City, Missouri, United States

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

St. John's Regional Health Center

Springfield, Missouri, United States

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, United States

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

David C. Pratt Cancer Center at St. John's Mercy

St Louis, Missouri, 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

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

St. James Healthcare Cancer Care

Butte, Montana, United States

Big Sky Oncology

Great Falls, Montana, United States

Frontier Cancer Center

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

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Kalispell Regional Medical Center

Kalispell, Montana, United States

Community Medical Center

Missoula, Montana, United States

Guardian Oncology and Center for Wellness

Missoula, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, United States

Tucker Center for Cancer Care at Orange Regional Medical Center

Middletown, New York, United States

Randolph Hospital

Asheboro, North Carolina, United States

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States

Moses Cone Regional Cancer Center at Wesley Long Community Hospital

Greensboro, North Carolina, United States

Annie Penn Cancer Center

Reidsville, North Carolina, United States

Rutherford Hospital

Rutherfordton, North Carolina, United States

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, United States

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital

Dayton, Ohio, United States

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Cancer Care Center

Dayton, Ohio, United States

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

CCOP - Dayton

Dayton, Ohio, United States

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Middletown Regional Hospital

Franklin, Ohio, United States

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Clinton Memorial Hospital

Wilmington, Ohio, United States

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

AnMed Cancer Center

Anderson, South Carolina, United States

CCOP - Greenville

Greenville, South Carolina, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

Kingsport, Tennessee, United States

CCOP - Scott and White Hospital

Temple, Texas, United States

American Fork Hospital

American Fork, Utah, United States

Sandra L. Maxwell Cancer Center

Cedar City, Utah, United States

Logan Regional Hospital

Logan, Utah, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center

Ogden, Utah, United States

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, United States

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

Southwest Virginia Regional Cancer Center at Wellmonth Health

Norton, Virginia, United States

St. Joseph Cancer Center

Bellingham, Washington, United States

Olympic Hematology and Oncology

Bremerton, Washington, United States

Columbia Basin Hematology

Kennewick, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Harborview Medical Center

Seattle, Washington, United States

Minor and James Medical, PLLC

Seattle, Washington, United States

Veterans Affairs Medical Center - Seattle

Seattle, Washington, United States

Group Health Central Hospital

Seattle, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Polyclinic First Hill

Seattle, Washington, United States

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Rockwood Clinic Cancer Treatment Center

Spokane, Washington, United States

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Countries

United States

References

Leichman L, Goldman BH, Benedetti JK, et al.: Oxaliplatin (OXP) plus protracted infusion 5-fluorouracil (PIFU) and external beam radiation (EBRT) prior to surgery (S) for potentially curable esophageal adenocarcinoma (EA): A Southwest Oncology Group (SWOG) phase II trial with molecular correlates (S0356). [Abstract] J Clin Oncol 27 (Suppl 15): A-4513, 2009.

Reference Type: RESULT

Leichman LP, Goldman BH, Bohanes PO, Lenz HJ, Thomas CR, Billingsley KG, Corless CL, Iqbal S, Gold PJ, Benedetti JK, Danenberg KD, Blanke CD. S0356: a phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. J Clin Oncol. 2011 Dec 1;29(34):4555-60. doi: 10.1200/JCO.2011.36.7490. Epub 2011 Oct 24.

Reference Type: DERIVED

PMID: 22025151 (View on PubMed)

Other Identifiers

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0356

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000371963

Identifier Type: -

Identifier Source: org_study_id