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

Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: oxaliplatin; Procedure: conventional surgery; Radiation: radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Cancer Center
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Highlands Oncology Group - Springdale
  • California
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Eden Medical Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants - Castro Valley
    • Fremont, California, United States, 94538
      • Valley Medical Oncology
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Larry G Strieff MD Medical Corporation
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Bay Area Breast Surgeons, Incorporated
    • Oakland, California, United States, 94609
      • Tom K Lee, Incorporated
    • Palm Springs, California, United States, 92262
      • Desert Regional Medical Center Comprehensive Cancer Center
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants - Pleasanton
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center - San Pablo Campus
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31403-3089
      • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Mt. Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Olathe, Kansas, United States, 66061
      • Olathe Cancer Center
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Butterworth Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grand Rapids, Michigan, United States, 49506
      • Metro Health Hospital
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Muskegon, Michigan, United States, 49442
      • Hackley Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Gape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Joplin, Missouri, United States, 64804
      • St. John's Regional Medical Center
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405-5309
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Great Falls, Montana, United States, 59405
      • Frontier Cancer Center
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
  • New York
    • Middletown, New York, United States, 10940-4199
      • Tucker Center for Cancer Care at Orange Regional Medical Center
  • North Carolina
    • Asheboro, North Carolina, United States, 27203-5400
      • Randolph Hospital
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Greensboro, North Carolina, United States, 27403-1198
      • Moses Cone Regional Cancer Center at Wesley Long Community Hospital
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Cancer Center
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Cancer Center
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37662
      • Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
  • Texas
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84103
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Virginia
    • Norton, Virginia, United States, 24273
      • Southwest Virginia Regional Cancer Center at Wellmonth Health
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99204-2967
      • Rockwood Clinic Cancer Treatment Center
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemo Plus RT, Surgery, Chemo; neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin

Drug: 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.; Other Names: 5-FU; 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.; Other Names: eloxatin; Procedure: conventional surgery; The surgical technique will depend upon the location and extent of tumor and individual surgeon preference.; Radiation: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response	Complete pathologic response assessed after chemoradiotherapy and surgery, defined as no evidence of residual disease on path review. Patients who did not receive surgery are assumed to have not responded.	10-16 weeks after beginning study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 3 years
Overall Survival	Measured from time of registration to death, or last contact date	0-5 years
Progression-free Survival	measured from date of registration to time of first documentation of progression by Response Evaluation Criteria in Solid Tumors (RECIST), death, or last contact date.	0-3 years

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lawrence P. Leichman, MD, Desert Regional Medical Center Comprehensive Cancer Center; Study Chair: Charles R. Thomas, MD, OHSU Knight Cancer Institute

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: July 8, 2004
• First Submitted That Met QC Criteria: July 9, 2004
• First Posted (Estimate): July 12, 2004

Study Record Updates

• Last Update Posted (Estimate): October 11, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: stage II esophageal cancer; stage III esophageal cancer; adenocarcinoma of the esophagus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil; Oxaliplatin
• Other Study ID Numbers: CDR0000371963; U10CA032102 (U.S. NIH Grant/Contract); S0356 (Other Identifier: SWOG)