Chemotherapy Induction and Chemoradiotherapy in Patients With Esophageal Carcinoma

Study Overview
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Brief Summary
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The aim of this study is the evaluate the feasibility and safety of chemotherapy induction treatment combined with cetuximab followed by chemoradiotherapy combined with cetuximab in the treatment of patients with non-metastatic esophageal cancer.

Detailed Description
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Patients with a locoregional carcinoma of the esophagus or gastro-esophageal junction have a low survival prognosis following surgical resection. In studies published to date no positive effect upon overall survival could be demonstrated for preoperative chemotherapy or chemoradiotherapy. However, patients with a complete remission following preoperative therapy show prolonged survival. This study design is based upon decreasing primary tumour and preventing oder delaying micrometastases by means of a chemo induction therapy, increasing R0 resection rates and preventing local recurrence by means of preoperative chemoradiotherapy, increasing the radiosensitivity of tumour cells through treatment combination with cetuximab, surgical resection of the locoregional primary tumour or definitive radiochemotherapy in case the primary tumour is inoperable. The aim of this study is therefore to evaluate the feasibility and safety of a 3-staged therapy approach including an EGFR antibody in the treatment of patients with potentially resectable esophageal cancer, as well as the evaluation of objective response rates to this preoperative therapy.

Official Title
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Chemotherapy Induction and Chemoradiotherapy Combined With Cetuximab Respectively in Patients With Non-Metastatic Esophageal Carcinoma: A Multicentric Phase II Study

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: 5-FU
* Drug: Cisplatin
* Drug: Taxotere
* Biological: Cetuximab
* Radiation: Radiation during chemoradio-immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent histologically confirmed esophageal cancer (squamous cell carcinoma) measurable, non-metastatic disease (uT1-4) no previous cancer therapy (chemotherapy, radiotherapy or resection) life expectancy > 3 months age > 18 years WHO Status ≤ 2 negative pregnancy test for women of child-bearing potential, and use of adequate contraception hematological status: neutrophiles ≥ 1,5x10E9/L, thrombocytes ≥ 100x10E9/L adequate renal function: serum creatinine ≤ 1,5 x ULN adequate liver function: alkaline phosphatase < 2,5 x ULN, total bilirubin < 1,5 x ULN Exclusion Criteria: pregnant or nursing women women of child-bearing potential without adequate contraception concomitant anti-tumoral therapy except study mandated procedures cervical esophageal cancer or diagnosis of metastases participation in other clinical trials within the last 30 days history of malignant disease within the last 5 years peripheral neuropathy (NCI CTC ≥ grade 1) concurrent active and serious non-malignant diseases: uncontrolled heart insufficiency, angina pectoris, hypertension or arrhythmias, liver disease, significant neurological or psychiatric conditions active infections

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Chemo induction therapy followed by chemoradiotherapy and surgical resection or definitive radiotherapy | Drug: 5-FU<br>* 750 mg/m2/d C.I. i.v.d1-5, d29-33 and 300 mg/m2/d C.I. i.v. on the days of radiotherapy<br>Drug: Cisplatin<br>* 15 mg/m2/d i.v. d1-5, d29-33<br>Drug: Taxotere<br>* 75 mg/m2/d i.v. d1 and d29, 15 mg/m2/d i.v. on d57, d64, d71 and d78<br>* Other names: Docetaxel;Biological: Cetuximab<br>* Cetuximab: 400 mg/m2 i.v. d1; 250mg/m2 weekly d8 through d85<br>* Other names: Erbitux;Radiation: Radiation during chemoradio-immunotherapy<br>* 39.6 Gy total dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Duration of study | 
| Percentage of complete remissions and resection rate |  | Duration of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of toxicities |  | Duration of study | 
| Evaluation of Quality of Life |  | Duration of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal cancer, Pre-operative, Chemo-immunotherapy, Radiochemo-immunotherapy, EGFR, Radiosensitivity, Resection