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

NCT ID: NCT00109850

Last Updated: 2015-11-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-05-31

Study Completion Date

2012-05-31

Brief Summary

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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

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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.

Conditions

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Esophageal Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment

Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.

Group Type EXPERIMENTAL

cetuximab

Intervention Type BIOLOGICAL

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.

cisplatin

Intervention Type DRUG

30mg/m\^2, bolus intravenous (IV), on Days 1 \& 8 of each cycle.

irinotecan hydrochloride

Intervention Type DRUG

65mg/m\^2, intravenous (IV) over 30 min, on Days 1 \& 8 of each cycle.

radiation therapy

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type BIOLOGICAL

cisplatin

30mg/m\^2, bolus intravenous (IV), on Days 1 \& 8 of each cycle.

Intervention Type DRUG

irinotecan hydrochloride

65mg/m\^2, intravenous (IV) over 30 min, on Days 1 \& 8 of each cycle.

Intervention Type DRUG

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.

Intervention Type RADIATION

Other Intervention Names

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Erbitux Platinol CPT-11 RT TRT

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charles R. Thomas, MD

Role: STUDY_CHAIR

OHSU Knight Cancer Institute

Charles D. Blanke, MD, FACP

Role: STUDY_CHAIR

OHSU Knight Cancer Institute

James L. Abbruzzese, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Lisa Hammond, MD

Role: STUDY_CHAIR

The University of Texas Health Science Center at San Antonio

Vivek Mehta, MD

Role: STUDY_CHAIR

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Locations

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Mobile Infirmary Medical Center

Mobile, Alabama, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Alta Bates Comprehensive Cancer Center

Berkeley, California, United States

Site Status

Providence Saint Joseph Medical Center - Burbank

Burbank, California, United States

Site Status

Peninsula Medical Center

Burlingame, California, United States

Site Status

Eden Medical Center

Castro Valley, California, United States

Site Status

Marin Cancer Institute at Marin General Hospital

Greenbrae, California, United States

Site Status

Sutter Health - Western Division Cancer Research Group

Greenbrae, California, United States

Site Status

Saint Rose Hospital

Hayward, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Highland General Hospital

Oakland, California, United States

Site Status

Alta Bates Summit Medical Center - Summit Campus

Oakland, California, United States

Site Status

CCOP - Bay Area Tumor Institute

Oakland, California, United States

Site Status

Desert Regional Medical Center Comprehensive Cancer Center

Palm Springs, California, United States

Site Status

Valley Care Medical Center

Pleasanton, California, United States

Site Status

University of California Davis Cancer Center

Sacramento, California, United States

Site Status

California Pacific Medical Center - California Campus

San Francisco, California, United States

Site Status

Doctors Medical Center - San Pablo Campus

San Pablo, California, United States

Site Status

CCOP - Santa Rosa Memorial Hospital

Sana Rosa, California, United States

Site Status

Sutter Solano Medical Center

Vallejo, California, United States

Site Status

Poudre Valley Hospital

Fort Collins, Colorado, United States

Site Status

Watson Clinic, LLC

Lakeland, Florida, United States

Site Status

Augusta Oncology Associates - Walton Way

Augusta, Georgia, United States

Site Status

Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler

Savannah, Georgia, United States

Site Status

St. Luke's Mountain States Tumor Institute - Boise

Boise, Idaho, United States

Site Status

Regional Cancer Center at Memorial Medical Center

Springfield, Illinois, United States

Site Status

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Site Status

Reid Hospital & Health Care Services, Incorporated

Richmond, Indiana, United States

Site Status

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Site Status

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Site Status

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Site Status

Southwest Medical Center

Liberal, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Site Status

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, United States

Site Status

Associates in Womens Health, PA - North Review

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Site Status

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States

Site Status

Mecosta County Medical Center

Big Rapids, Michigan, United States

Site Status

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Site Status

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

Site Status

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States

Site Status

Spectrum Health Hospital - Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Metro Health Hospital

Grand Rapids, Michigan, United States

Site Status

Holland Community Hospital

Holland, Michigan, United States

Site Status

Hackley Hospital

Muskegon, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

Site Status

St. John's Regional Health Center

Springfield, Missouri, United States

Site Status

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, United States

Site Status

Saint Louis University Cancer Center

St Louis, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Site Status

Northern Rockies Radiation Oncology Center

Billings, Montana, United States

Site Status

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Site Status

Billings Clinic - Downtown

Billings, Montana, United States

Site Status

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

Site Status

St. James Healthcare Cancer Care

Butte, Montana, United States

Site Status

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Site Status

Great Falls, Montana, United States

Site Status

St. Peter's Hospital

Helena, Montana, United States

Site Status

Glacier Oncology, PLLC

Kalispell, Montana, United States

Site Status

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Site Status

Kalispell Regional Medical Center

Kalispell, Montana, United States

Site Status

Community Medical Center

Missoula, Montana, United States

Site Status

Guardian Oncology and Center for Wellness

Missoula, Montana, United States

Site Status

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Site Status

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

Site Status

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, United States

Site Status

Interlakes Oncology/Hematology PC

Rochester, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States

Site Status

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, United States

Site Status

Grandview Hospital

Dayton, Ohio, United States

Site Status

Good Samaritan Hospital

Dayton, Ohio, United States

Site Status

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Samaritan North Cancer Care Center

Dayton, Ohio, United States

Site Status

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Dayton, Ohio, United States

Site Status

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Site Status

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

Site Status

Middletown Regional Hospital

Middletown, Ohio, United States

Site Status

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Site Status

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

Site Status

Legacy Mount Hood Medical Center

Gresham, Oregon, United States

Site Status

Providence Milwaukie Hospital

Milwaukie, Oregon, United States

Site Status

Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center

Portland, Oregon, United States

Site Status

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Site Status

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Site Status

Providence St. Vincent Medical Center

Portland, Oregon, United States

Site Status

Legacy Emanuel Hospital and Health Center & Children's Hospital

Portland, Oregon, United States

Site Status

Northwest Cancer Specialists at Rose Quarter Cancer Center

Portland, Oregon, United States

Site Status

Oregon Health & Science University Cancer Institute

Portland, Oregon, United States

Site Status

Salem Hospital Regional Cancer Care Services

Salem, Oregon, United States

Site Status

Legacy Meridian Park Hospital

Tualatin, Oregon, United States

Site Status

Roper St. Francis Cancer Center at Roper Hospital

Charleston, South Carolina, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

CCOP - Greenville

Greenville, South Carolina, United States

Site Status

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

Kingsport, Tennessee, United States

Site Status

U.T. Cancer Institute at University of Tennessee Medical Center

Knoxville, Tennessee, United States

Site Status

Danville Regional Medical Center

Danville, Virginia, United States

Site Status

Southwest Virginia Regional Cancer Center

Norton, Virginia, United States

Site Status

St. Joseph Cancer Center

Bellingham, Washington, United States

Site Status

Olympic Hematology and Oncology

Bremerton, Washington, United States

Site Status

Columbia Basin Hematology

Kennewick, Washington, United States

Site Status

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

Minor and James Medical, PLLC

Seattle, Washington, United States

Site Status

Group Health Central Hospital

Seattle, Washington, United States

Site Status

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Site Status

Polyclinic First Hill

Seattle, Washington, United States

Site Status

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Site Status

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Site Status

Southwest Washington Medical Center Cancer Center

Vancouver, Washington, United States

Site Status

Northwest Cancer Specialists at Vancouver Cancer Center

Vancouver, Washington, United States

Site Status

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

Site Status

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Site Status

Countries

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United States

Other Identifiers

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S0414

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000426442

Identifier Type: -

Identifier Source: org_study_id