Clinical trial NCT00109850: S0414 Cetuximab, Combo Chemo, and RT in Locally Advanced Esophageal Cancer
Official title: Cetuximab Plus Cisplatin, Irinotecan and Thoracic Radiotherapy (TRT) for Locally Advanced (Non-Metastatic), Clinically Unresectable Esophageal Cancer: A Phase II Trial With Molecular Correlates
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage III esophageal cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-05-04
Enrollment: 22
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: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of esophageal cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients with locally advanced esophageal cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Determine the 2-year overall survival of patients with previously untreated, clinically unresectable, locally advanced squamous cell carcinoma or adenocarcinoma of the esophagus treated with cetuximab, cisplatin, irinotecan, and thoracic radiotherapy.

Secondary

* Determine the toxicity profile of this regimen in these patients.
* Determine the probability of objective response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen.
* Determine the time to progression in patients with measurable disease treated with this regimen.
* Correlate, preliminarily, gene expression (RNA) levels and germline polymorphisms of genes involved in DNA repair (e.g., ECRCC-1 and XRCC-1), drug metabolism (e.g., UGT1A1), and the epidermal growth factor receptor (EGFR) pathway (e.g., EGFR, interleukin-8, and vascular endothelial growth factor) with response, time to progression, overall survival, and toxicity in patients treated with this regimen. (This will not be completed as this study was closed due to poor accrual.)

OUTLINE: This is a multicenter study.

Patients receive cetuximab intravenous (IV) over 1-2 hours on days 1, 8, and 15. Patients also receive cisplatin IV and irinotecan IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 3, patients undergo thoracic radiotherapy once daily 5 days a week for 5-6 weeks (total of 28 treatments).

After completion of study treatment, patients are followed at 4 weeks and then every 3-6 months for up to 5 years after study entry.

PROJECTED ACCRUAL: A total of 75-100 patients (75 with adenocarcinoma and 25 with squamous cell carcinoma) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (≥ 20 cm from the incisors\*) or the gastroesophageal junction (confined to ≤ 2 cm into the gastric cardia)

  * Disease confined to the esophagus or peri-esophageal soft tissue
  * T4, M0 disease
  * Surgically unresectable disease by esophageal endoscopic ultrasonography OR medically unresectable disease

NOTE: \*Patients with primary disease \< 26 cm from the incisors must undergo bronchoscopy AND have negative cytology within the past 4 weeks

* Measurable or non-measurable disease by x-ray, CT scan and/or MRI, or physical examination within the past 4 weeks (for measurable disease) or within the past 6 weeks (for non-measurable disease)
* Tumor specimens available
* No recurrent disease

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
* White Blood Cell (WBC) count ≥ 3,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 10.0 g/dL

Hepatic

* Albumin normal
* Bilirubin normal
* Alkaline phosphatase normal
* Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times upper limit of normal

Renal

* Creatinine clearance \> 50 mL/min

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No prior severe reaction to monoclonal antibodies
* 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

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
* No concurrent cobalt-60

Surgery

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

Primary outcomes:
measure: Overall Survival at 2 Years
timeFrame: 0-2 years
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 every two cycles of chemotherapy.
measure: Objective Response (Confirmed and Unconfined, Complete and Partial)
timeFrame: at week 16, then every 3 months until progression
measure: Progression Free Survival
timeFrame: 0 - 5 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Burlingame
country: United States
facility: Peninsula Medical Center
state: California
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Institute at Marin General Hospital
state: California
city: Greenbrae
country: United States
facility: Sutter Health - Western Division Cancer Research Group
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
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: CCOP - Bay Area Tumor Institute
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: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - California Campus
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center - San Pablo Campus
state: California
city: Sana Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Vallejo
country: United States
facility: Sutter Solano Medical Center
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Lakeland
country: United States
facility: Watson Clinic, LLC
state: Florida
city: Augusta
country: United States
facility: Augusta Oncology Associates - Walton Way
state: Georgia
city: Savannah
country: United States
facility: Curtis & 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: Boise
country: United States
facility: St. Luke's Mountain States Tumor Institute - Boise
state: Idaho
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, Incorporated
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: 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: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health 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: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
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: Josephine Ford Cancer Center at Henry Ford Hospital
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: Spectrum Health Hospital - Butterworth Campus
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: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
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: Great Falls Clinic - Main Facility
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 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: 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: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
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: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center & Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists at Rose Quarter Cancer Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University Cancer Institute
state: Oregon
city: Salem
country: United States
facility: Salem Hospital Regional Cancer Care Services
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Charleston
country: United States
facility: Roper St. Francis Cancer Center at Roper Hospital
state: South Carolina
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Knoxville
country: United States
facility: U.T. Cancer Institute at University of Tennessee Medical Center
state: Tennessee
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Norton
country: United States
facility: Southwest Virginia Regional Cancer 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: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists at Vancouver Cancer 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: OHSU Knight Cancer Institute
name: Charles R. Thomas, MD
role: STUDY_CHAIR
affiliation: OHSU Knight Cancer Institute
name: Charles D. Blanke, MD, FACP
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: James L. Abbruzzese, MD
role: STUDY_CHAIR
affiliation: The University of Texas Health Science Center at San Antonio
name: Lisa Hammond, MD
role: STUDY_CHAIR
affiliation: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
name: Vivek Mehta, MD
role: STUDY_CHAIR
References: