S0414 Cetuximab, Combo Chemo, and RT in Locally Advanced Esophageal Cancer

This study has been terminated.
(Closed due to poor accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00109850
First received: May 3, 2005
Last updated: July 20, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Biological: cetuximab
Drug: cisplatin
Drug: irinotecan hydrochloride
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Overall Survival at 2 Years [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
    Measured from time of registration to date of death due to any cause, or last contact date


Secondary Outcome Measures:
  • Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events after every two cycles of chemotherapy. ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

  • Objective Response (Confirmed and Unconfined, Complete and Partial) [ Time Frame: at week 16, then every 3 months until progression ] [ Designated as safety issue: No ]
    Complete response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. Partial response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration.

  • Progression Free Survival [ Time Frame: 0 - 5 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progression or symptomatic deterioration. Patients last known to be alive and progression-free are censored at date of last contact.


Enrollment: 22
Study Start Date: May 2005
Study Completion Date: May 2012
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
Biological: cetuximab
400mg/m^2 loading dose, intravenous (IV) over 120 min, day 1 of cycle 1 only. 250mg/m^2 maintenance dose, IV over 60 min, Days 8 & 15 of Cycle 1 and Days 1, 8, and 15 of subsequent cycles.
Other Name: Erbitux
Drug: cisplatin
30mg/m^2, bolus intravenous (IV), on Days 1 & 8 of each cycle.
Other Name: Platinol
Drug: irinotecan hydrochloride
65mg/m^2, intravenous (IV) over 30 min, on Days 1 & 8 of each cycle.
Other Name: CPT-11
Radiation: radiation therapy
The total dose to the prescription point will be 5,040 cGy given in 28 fractions. The patient will be treated with one fraction per day with all fields treated per day. 180 cGy will be delivered to the isocenter. The dose variation in the planning target volume (PTV) will be +7% and -5% of the prescription point dose.
Other Names:
  • RT
  • TRT

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00109850

  Hide Study Locations
Locations
United States, Alabama
Mobile Infirmary Medical Center
Mobile, Alabama, United States, 36652-2144
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Alta Bates Comprehensive Cancer Center
Berkeley, California, United States, 94704
Providence Saint Joseph Medical Center - Burbank
Burbank, California, United States, 91505
Peninsula Medical Center
Burlingame, California, United States, 94010
Eden Medical Center
Castro Valley, California, United States, 94546
Marin Cancer Institute at Marin General Hospital
Greenbrae, California, United States, 94904
Sutter Health - Western Division Cancer Research Group
Greenbrae, California, United States, 94904
Saint Rose Hospital
Hayward, California, United States, 94545
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
CCOP - Bay Area Tumor Institute
Oakland, California, United States, 94609
Highland General Hospital
Oakland, California, United States, 94602
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, United States, 94609
Desert Regional Medical Center Comprehensive Cancer Center
Palm Springs, California, United States, 92262
Valley Care Medical Center
Pleasanton, California, United States, 94588
University of California Davis Cancer Center
Sacramento, California, United States, 95817
California Pacific Medical Center - California Campus
San Francisco, California, United States, 94118
Doctors Medical Center - San Pablo Campus
San Pablo, California, United States, 94806
CCOP - Santa Rosa Memorial Hospital
Sana Rosa, California, United States, 95405
Sutter Solano Medical Center
Vallejo, California, United States, 94589
United States, Colorado
Poudre Valley Hospital
Fort Collins, Colorado, United States, 80524
United States, Florida
Watson Clinic, LLC
Lakeland, Florida, United States, 33804-5000
United States, Georgia
Augusta Oncology Associates - Walton Way
Augusta, Georgia, United States, 30901
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
Savannah, Georgia, United States, 31405
United States, Idaho
St. Luke's Mountain States Tumor Institute - Boise
Boise, Idaho, United States, 83712
United States, Illinois
Regional Cancer Center at Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services, Incorporated
Richmond, Indiana, United States, 47374
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Southwest Medical Center
Liberal, Kansas, United States, 67901
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Tammy Walker Cancer Center at Salina Regional Health Center
Salina, Kansas, United States, 67401
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67042
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
CCOP - Wichita
Wichita, Kansas, United States, 67214
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67203
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Wesley Medical Center
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0293
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, United States, 49017
Mecosta County Medical Center
Big Rapids, Michigan, United States, 49307
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
Metro Health Hospital
Grand Rapids, Michigan, United States, 49506
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, United States, 49503
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
Spectrum Health Hospital - Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Holland Community Hospital
Holland, Michigan, United States, 49423
Hackley Hospital
Muskegon, Michigan, United States, 49442
Munson Medical Center
Traverse City, Michigan, United States, 49684
United States, Missouri
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Saint Louis University Cancer Center
Saint Louis, Missouri, United States, 63110
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65802
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
St. John's Regional Health Center
Springfield, Missouri, United States, 65804
United States, Montana
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
St. Vincent Healthcare Cancer Care Services
Billings, Montana, United States, 59101
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
St. James Healthcare Cancer Care
Butte, Montana, United States, 59701
Great Falls, Montana, United States, 59405
Great Falls Clinic - Main Facility
Great Falls, Montana, United States, 59405
St. Peter's Hospital
Helena, Montana, United States, 59601
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Kalispell Medical Oncology at KRMC
Kalispell, Montana, United States, 59901
Guardian Oncology and Center for Wellness
Missoula, Montana, United States, 59804
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
Community Medical Center
Missoula, Montana, United States, 59801
United States, Nebraska
Good Samaritan Cancer Center at Good Samaritan Hospital
Kearney, Nebraska, United States, 68848-1990
United States, New York
Interlakes Oncology/Hematology PC
Rochester, New York, United States, 14623
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
United States, Ohio
McDowell Cancer Center at Akron General Medical Center
Akron, Ohio, United States, 44307
CCOP - Dayton
Dayton, Ohio, United States, 45429
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
Grandview Hospital
Dayton, Ohio, United States, 45405
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
Middletown Regional Hospital
Middletown, Ohio, United States, 45044
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
United States, Oregon
Legacy Mount Hood Medical Center
Gresham, Oregon, United States, 97030
Providence Milwaukie Hospital
Milwaukie, Oregon, United States, 97222
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
Portland, Oregon, United States, 97210
Providence St. Vincent Medical Center
Portland, Oregon, United States, 97225
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213-2967
Northwest Cancer Specialists at Rose Quarter Cancer Center
Portland, Oregon, United States, 97227
Oregon Health & Science University Cancer Institute
Portland, Oregon, United States, 97239-3098
Legacy Emanuel Hospital and Health Center & Children's Hospital
Portland, Oregon, United States, 97227
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Salem Hospital Regional Cancer Care Services
Salem, Oregon, United States, 97309-5014
Legacy Meridian Park Hospital
Tualatin, Oregon, United States, 97062
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Roper St. Francis Cancer Center at Roper Hospital
Charleston, South Carolina, United States, 29401
CCOP - Greenville
Greenville, South Carolina, United States, 29615
United States, Tennessee
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
Kingsport, Tennessee, United States, 37662
U.T. Cancer Institute at University of Tennessee Medical Center
Knoxville, Tennessee, United States, 37920-6999
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
Southwest Virginia Regional Cancer Center
Norton, Virginia, United States, 24273
United States, Washington
St. Joseph Cancer Center
Bellingham, Washington, United States, 98225
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Columbia Basin Hematology
Kennewick, Washington, United States, 99336
Skagit Valley Hospital Cancer Care Center
Mt. Vernon, Washington, United States, 98273
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
Minor and James Medical, PLLC
Seattle, Washington, United States, 98104
Group Health Central Hospital
Seattle, Washington, United States, 98112
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195-6043
Polyclinic First Hill
Seattle, Washington, United States, 98122
Harborview Medical Center
Seattle, Washington, United States, 98104
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98122-4307
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Southwest Washington Medical Center Cancer Center
Vancouver, Washington, United States, 98668
Northwest Cancer Specialists at Vancouver Cancer Center
Vancouver, Washington, United States, 98684
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
United States, Wyoming
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Charles R. Thomas, MD OHSU Knight Cancer Institute
Study Chair: Charles D. Blanke, MD, FACP OHSU Knight Cancer Institute
Study Chair: James L. Abbruzzese, MD M.D. Anderson Cancer Center
Study Chair: Lisa Hammond, MD The University of Texas Health Science Center at San Antonio
Study Chair: Vivek Mehta, MD Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00109850     History of Changes
Other Study ID Numbers: CDR0000426442, S0414, U10CA032102
Study First Received: May 3, 2005
Results First Received: June 14, 2012
Last Updated: July 20, 2012
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage III esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Irinotecan
Cetuximab
Cisplatin
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014