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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00086996
• Other study ID #: CDR0000371963
• Secondary ID: U10CA032102S0356
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2004
• Last updated: September 4, 2013
• Start date: September 2004
• Est. completion date: August 2011

Study information

• Verified date: September 2013
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: August 2011
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

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.
• 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.

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.

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	American Fork Hospital	American Fork	Utah
United States	Providence Cancer Center	Anchorage	Alaska
United States	AnMed Cancer Center	Anderson	South Carolina
United States	Randolph Hospital	Asheboro	North Carolina
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
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	Highlands Oncology Group - Springdale	Bentonville	Arkansas
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	Boston University Cancer Research Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
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	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
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	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
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	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Valley Medical Oncology	Fremont	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri
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	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	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	St. John's Regional Medical Center	Joplin	Missouri
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	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Southwest Medical Center	Liberal	Kansas
United States	Logan Regional Hospital	Logan	Utah
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	New York
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	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Good Samaritan Regional Health Center	Mt. Vernon	Illinois
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Hackley Hospital	Muskegon	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia
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	Highland General Hospital	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee, Incorporated	Oakland	California
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Olathe Cancer Center	Olathe	Kansas
United States	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Valley Care Medical Center	Pleasanton	California
United States	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Annie Penn Cancer Center	Reidsville	North Carolina
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California Davis Cancer Center	Sacramento	California
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	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	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Rockwood Clinic Cancer Treatment Center	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	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	St. John's Regional Health Center	Springfield	Missouri
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	St. Francis Comprehensive Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
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	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	Overall Survival	Measured from time of registration to death, or last contact date	0-5 years	No
Secondary	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	No