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

Primary Purpose

Esophageal Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

cetuximab

cisplatin

irinotecan hydrochloride

radiation therapy

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage III esophageal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mobile Infirmary Medical Center
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Alta Bates Comprehensive Cancer Center
Providence Saint Joseph Medical Center - Burbank
Peninsula Medical Center
Eden Medical Center
Marin Cancer Institute at Marin General Hospital
Sutter Health - Western Division Cancer Research Group
Saint Rose Hospital
USC/Norris Comprehensive Cancer Center and Hospital
Highland General Hospital
Alta Bates Summit Medical Center - Summit Campus
CCOP - Bay Area Tumor Institute
Desert Regional Medical Center Comprehensive Cancer Center
Valley Care Medical Center
University of California Davis Cancer Center
California Pacific Medical Center - California Campus
Doctors Medical Center - San Pablo Campus
CCOP - Santa Rosa Memorial Hospital
Sutter Solano Medical Center
Poudre Valley Hospital
Watson Clinic, LLC
Augusta Oncology Associates - Walton Way
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
St. Luke's Mountain States Tumor Institute - Boise
Regional Cancer Center at Memorial Medical Center
St. Francis Hospital and Health Centers - Beech Grove Campus
Reid Hospital & Health Care Services, Incorporated
Cancer Center of Kansas, PA - Chanute
Cancer Center of Kansas, PA - Dodge City
Cancer Center of Kansas, PA - El Dorado
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Cancer Center of Kansas, PA - Kingman
Southwest Medical Center
Cancer Center of Kansas, PA - Newton
Cancer Center of Kansas, PA - Parsons
Cancer Center of Kansas, PA - Pratt
Cancer Center of Kansas, PA - Salina
Tammy Walker Cancer Center at Salina Regional Health Center
Cancer Center of Kansas, PA - Wellington
Associates in Womens Health, PA - North Review
Cancer Center of Kansas, PA - Medical Arts Tower
Cancer Center of Kansas, PA - Wichita
CCOP - Wichita
Via Christi Cancer Center at Via Christi Regional Medical Center
Wesley Medical Center
Cancer Center of Kansas, PA - Winfield
Markey Cancer Center at University of Kentucky Chandler Medical Center
University of Michigan Comprehensive Cancer Center
Battle Creek Health System Cancer Care Center
Mecosta County Medical Center
Josephine Ford Cancer Center at Henry Ford Hospital
CCOP - Grand Rapids
Lacks Cancer Center at Saint Mary's Health Care
Spectrum Health Hospital - Butterworth Campus
Metro Health Hospital
Holland Community Hospital
Hackley Hospital
Munson Medical Center
CCOP - Kansas City
Saint Louis University Cancer Center
CCOP - Cancer Research for the Ozarks
St. John's Regional Health Center
Hulston Cancer Center at Cox Medical Center South
CCOP - Montana Cancer Consortium
Hematology-Oncology Centers of the Northern Rockies - Billings
Northern Rockies Radiation Oncology Center
St. Vincent Healthcare Cancer Care Services
Billings Clinic - Downtown
Bozeman Deaconess Cancer Center
St. James Healthcare Cancer Care
Great Falls Clinic - Main Facility
St. Peter's Hospital
Glacier Oncology, PLLC
Kalispell Medical Oncology at KRMC
Kalispell Regional Medical Center
Community Medical Center
Guardian Oncology and Center for Wellness
Montana Cancer Specialists at Montana Cancer Center
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Good Samaritan Cancer Center at Good Samaritan Hospital
Interlakes Oncology/Hematology PC
James P. Wilmot Cancer Center at University of Rochester Medical Center
Wayne Memorial Hospital, Incorporated
McDowell Cancer Center at Akron General Medical Center
Grandview Hospital
Good Samaritan Hospital
David L. Rike Cancer Center at Miami Valley Hospital
Samaritan North Cancer Care Center
Veterans Affairs Medical Center - Dayton
CCOP - Dayton
Blanchard Valley Medical Associates
Charles F. Kettering Memorial Hospital
Middletown Regional Hospital
UVMC Cancer Care Center at Upper Valley Medical Center
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Legacy Mount Hood Medical Center
Providence Milwaukie Hospital
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
Providence Cancer Center at Providence Portland Medical Center
CCOP - Columbia River Oncology Program
Providence St. Vincent Medical Center
Legacy Emanuel Hospital and Health Center & Children's Hospital
Northwest Cancer Specialists at Rose Quarter Cancer Center
Oregon Health & Science University Cancer Institute
Salem Hospital Regional Cancer Care Services
Legacy Meridian Park Hospital
Roper St. Francis Cancer Center at Roper Hospital
Hollings Cancer Center at Medical University of South Carolina
CCOP - Greenville
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
U.T. Cancer Institute at University of Tennessee Medical Center
Danville Regional Medical Center
Southwest Virginia Regional Cancer Center
St. Joseph Cancer Center
Olympic Hematology and Oncology
Columbia Basin Hematology
Skagit Valley Hospital Cancer Care Center
Fred Hutchinson Cancer Research Center
Harborview Medical Center
Minor and James Medical, PLLC
Group Health Central Hospital
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Polyclinic First Hill
University Cancer Center at University of Washington Medical Center
Cancer Care Northwest - Spokane South
Southwest Washington Medical Center Cancer Center
Northwest Cancer Specialists at Vancouver Cancer Center
Wenatchee Valley Medical Center
Welch Cancer Center at Sheridan Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Overall Survival at 2 Years

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

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)

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

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.

Full Information

NCT ID

NCT00109850

First Posted

May 3, 2005

Last Updated

November 16, 2015

Sponsor

SWOG Cancer Research Network

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00109850

Brief Title

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

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Terminated

Why Stopped

Closed due to poor accrual

Study Start Date

May 2005 (undefined)

Primary Completion Date

September 2009 (Actual)

Study Completion Date

May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

SWOG Cancer Research Network

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Cancer

Keywords

adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage III esophageal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

cetuximab

Other Intervention Name(s)

Erbitux

Intervention Description

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

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

Platinol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Other Intervention Name(s)

CPT-11

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Other Intervention Name(s)

RT, TRT

Intervention Description

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.

Primary Outcome Measure Information:

Title

Overall Survival at 2 Years

Description

Measured from time of registration to date of death due to any cause, or last contact date

Time Frame

0-2 years

Secondary Outcome Measure Information:

Title

Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug

Description

Time Frame

Patients were assessed for adverse events after every two cycles of chemotherapy.

Title

Objective Response (Confirmed and Unconfined, Complete and Partial)

Description

Time Frame

at week 16, then every 3 months until progression

Title

Progression Free Survival

Description

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.

Time Frame

0 - 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials: