Clinical trial NCT00086996: S0356 Oxaliplatin, 5-FU, Radiation Therapy (RT), Surgery for Pts With Stage II or III Cancer of Esophagus or Gastroesophageal (GE) Junction
Official title: Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-12
Enrollment: 98
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 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.

Eligibility 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

Primary outcomes:
measure: Pathological Complete Response
timeFrame: 10-16 weeks after beginning study treatment
Secondary outcomes:
measure: Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
timeFrame: Up to 3 years
measure: Overall Survival
timeFrame: 0-5 years
measure: Progression-free Survival
timeFrame: 0-3 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Anchorage
country: United States
facility: Providence Cancer Center
state: Alaska
city: Bentonville
country: United States
facility: Highlands Oncology Group - Springdale
state: Arkansas
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants - Castro Valley
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Breast Surgeons, Incorporated
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Larry G Strieff MD Medical Corporation
state: California
city: Oakland
country: United States
facility: Tom K Lee, Incorporated
state: California
city: Palm Springs
country: United States
facility: Desert Regional Medical Center Comprehensive Cancer Center
state: California
city: Pleasanton
country: United States
facility: Valley Care Medical Center
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants - Pleasanton
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center - San Pablo Campus
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Mt. Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
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: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Olathe
country: United States
facility: Olathe Cancer Center
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Cancer Center
state: Kansas
city: Topeka
country: United States
facility: St. Francis Comprehensive Cancer Center
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
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: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
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: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Gape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Joplin
country: United States
facility: St. John's Regional Medical Center
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
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: Frontier Cancer Center
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: 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 Medical Oncology at KRMC
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: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Middletown
country: United States
facility: Tucker Center for Cancer Care at Orange Regional Medical Center
state: New York
city: Asheboro
country: United States
facility: Randolph Hospital
state: North Carolina
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Greensboro
country: United States
facility: Moses Cone Regional Cancer Center at Wesley Long Community Hospital
state: North Carolina
city: Reidsville
country: United States
facility: Annie Penn Cancer Center
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
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: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Cedar City
country: United States
facility: Sandra L. Maxwell Cancer Center
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Norton
country: United States
facility: Southwest Virginia Regional Cancer Center at Wellmonth Health
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: 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: Veterans Affairs Medical Center - Seattle
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: Spokane
country: United States
facility: Rockwood Clinic Cancer Treatment Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
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: OHSU Knight Cancer Institute
name: Charles R. Thomas, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.