Cisplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients With Esophageal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin and capecitabine, work in different ways to kill tumor cells or stop them from growing. Radiation therapy uses high-energy x-rays to kill tumor cells. 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 tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving cisplatin together with capecitabine and radiation therapy is more effective with or without cetuximab in treating esophageal cancer. PURPOSE: This randomized phase II/III trial is studying the side effects and how well giving cisplatin together with capecitabine, radiation therapy, and cetuximab works compared with giving cisplatin, capecitabine, and radiation therapy without cetuximab in treating patients with esophageal cancer.

Detailed Description
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OBJECTIVES: Primary To determine whether the addition of cetuximab to definitive chemoradiotherapy comprising cisplatin, capecitabine, and radiotherapy shows evidence of enhanced overall survival in patients with carcinoma of the esophagus. To determine the safety of this regimen in these patients. To determine the feasibility of this regimen in these patients. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cisplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-84. Beginning in week 7 patients also undergo radiotherapy 5 days a week for 5 weeks (weeks 7-11). Treatment continues in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive cisplatin and capecitabine and undergo radiotherapy as in arm I. Patients also receive cetuximab IV over 1-2 hours on day 1 in weeks 1-12. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life and health economics are assessed at baseline, during treatment, and at pre-specified time points during follow-up. After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then annually for a minimum of 5 years.

Official Title
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A Randomised Phase II/III Multi-Centre Clinical Trial of Definitive Chemotherapy, With or Without Cetuximab, in Carcinoma of the Oesophagus

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: capecitabine
* Drug: cisplatin
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed carcinoma of the esophagus Adenocarcinoma Squamous cell Undifferentiated carcinoma Siewert type I tumor of the gastroesophageal junction Localized, nonmetastatic disease (T1-4, N0-1) confirmed by endoscopic ultrasound (EUS) and spiral CT scan Total disease length (primary and lymph nodes) < 10 cm by EUS Not suitable for surgery (either for medical reasons or patient's choice) No metastatic disease (i.e., M1a or M1b according to UICC TNM version 6) No significant (> 2 cm) extension of tumor into the stomach PATIENT CHARACTERISTICS: WHO performance status 0-1 Absolute neutrophil count ≥ 1,500/mm³ White blood cell count ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL (should be corrected to > 10 g/dL before treatment) Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT/AST ≤ 2.5 times ULN Alkaline phosphatase ≤ 3 times ULN Glomerular filtration rate > 40 mL/min OR > 60 mL/min estimated by Cockcroft-Gault formula Adequate cardiac ejection fraction ≥ 40% by MUGA or ECHO FEV_1 ≥ 1 L by spirometry Not pregnant Negative pregnancy test Fertile patients must use effective contraception No malignancy within the past 5 years No unstable angina, uncontrolled hypertension, cardiac failure, or other clinically significant cardiac disease No major trauma within the past 4 weeks No known dihydropyrimidine dehydrogenase deficiency No hearing impairment or sensory-motor neuropathy > grade 2 PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior sorivudine and analogues At least 4 weeks since prior major surgery At least 4 weeks since prior monoclonal antibody At least 3 months since prior radiotherapy No prior treatment for invasive esophageal carcinoma or gastroesophageal junction carcinoma (not including photodynamic therapy or laser therapy for high-grade dysplasia/carcinoma in situ) No other prior treatment for this malignancy that would compromise the ability to deliver definitive mediastinal chemoradiotherapy or compromise survival

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemo-radiotherapy<br> | Drug: capecitabine<br> <br> Drug: cisplatin<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Chemo-radiotherapy plus cetuximab<br> | Biological: cetuximab<br> <br> Drug: capecitabine<br> <br> Drug: cisplatin<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-failure rate at 24 weeks |  |  | 
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility |  |  | 
| Toxicity |  |  | 
| Quality of life |  |  | 
| Quality of assurance |  |  | 
| Health economics |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage IA esophageal cancer, stage IB esophageal cancer, stage IIA esophageal cancer, stage IIB esophageal cancer, stage IIIA esophageal cancer, stage IIIB esophageal cancer, stage IIIC esophageal cancer