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

Phase 2
Terminated
Conditions
Esophageal Cancer
Interventions
Biological: cetuximab
Radiation: radiation therapy
Registration Number
NCT00109850
Lead Sponsor
SWOG Cancer Research Network
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
22
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TreatmentcetuximabCetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
TreatmentcisplatinCetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
Treatmentirinotecan hydrochlorideCetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
Treatmentradiation therapyCetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
Primary Outcome Measures
NameTimeMethod
Overall Survival at 2 Years0-2 years

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

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival0 - 5 years

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.

Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study DrugPatients were assessed for adverse events after every two cycles of chemotherapy.

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)at week 16, then every 3 months until progression

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.

Trial Locations

Locations (131)

Mobile Infirmary Medical Center

🇺🇸

Mobile, Alabama, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Alta Bates Comprehensive Cancer Center

🇺🇸

Berkeley, California, United States

Providence Saint Joseph Medical Center - Burbank

🇺🇸

Burbank, California, United States

Peninsula Medical Center

🇺🇸

Burlingame, California, United States

Eden Medical Center

🇺🇸

Castro Valley, California, United States

Marin Cancer Institute at Marin General Hospital

🇺🇸

Greenbrae, California, United States

Sutter Health - Western Division Cancer Research Group

🇺🇸

Greenbrae, California, United States

Saint Rose Hospital

🇺🇸

Hayward, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

🇺🇸

Los Angeles, California, United States

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Mobile Infirmary Medical Center
🇺🇸Mobile, Alabama, United States

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