Study of Combination of Cetuximab and Radiotherapy Added to the Standard Treatment for Oesophageal Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the addition of the combination between cetuximab and radiotherapy to the standard chemotherapy for resectable oesophageal cancer is safe and adds efficacy.

Detailed Description
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This study aims at developing a novel strategy to optimize the treatment of oesophageal adenocarcinoma and gastro-oesophageal junctional tumors with curative intent. Surgery in combination with peri-operative chemotherapy, using the combination epirubicin, cisplatin and 5-FU, as defined by the recent MAGIC trial, results in 13% increase in 5-yr survival. To improve the outcome of patients with this disease we hypothesize that the addition of pre-operative combined cetuximab-radiotherapy (cetux-RT) treatment could improve the outcome of this patient category through better local control.

Official Title
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Multi-Modality Treatment of Resectable Oesophageal Adenocarcinoma Using Peri-operative Chemotherapy With Additional Pre-operative Combined Radiotherapy and Cetuximab

Conditions
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Resectable Esophageal Cancer

Intervention / Treatment
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* Drug: cetuximab
* Radiation: radiotherapy to oesophageal tumour


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven resectable adenocarcinoma of the lower oesophagus and gastric-oesophageal junction Tumour stage: T2-3 N0-1 M0, as assessed by endoscopic ultrasound and CT-scan of thorax and abdomen and ultrasound neck region. For the patients treated in this study the gastro-oesophageal junctional tumors will be staged as oesophageal tumors with respect to their lymphnode metastases. Age >18y and written informed consent after at least 4 days of deliberation time from the moment the patient information has been given and has been explained. Weight loss < 10% in 0.5 yr WHO performance status 0-1 No prior radiotherapy or chemotherapy for the adenocarcinoma of the oesophagus Exclusion Criteria: Previous malignancy other than basal cell carcinoma of the skin or local resection for cervical carcinoma in situ. Inadequate organ function as defined by: Inadequate haematology (Hb < 5,5 mmol/L (red blood cell transfusions are allowed to increase the Hb at the discretion of the investigator) - neutrophils < 1,5 109/L -platelets <100*109/L), Liver enzyme elevation (bili > 1,5*ULN - ASAT > 2,5*ULN - ALAT > 2,5*ULN) or Impaired renal function (creatinine clearance by cockcroft < 60 cc/min) Proteinuria >1,0gr/24hr Tumour stage: M1a and/or tumour length > 8 cm and/or > 5 cm radially Major surgery within 4 weeks prior to the start of study treatment Bleeding disorder Known allergy to one of the study drugs used Use of any substance known to interfere with the chemotherapy clearance Previous radiotherapy to the chest Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments Uncontrolled angina pectoris; cardiac failure or clinically significant arrhythmias Continuous use of immunosuppressive agents Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine Prior exposure to anti-EGFR targeting agents. Hearing loss > 25 dB under normal Neurotoxicity > CTC grade 1 Pregnancy or breast feeding Patients (M/F) with reproductive potential not implementing adequate contraceptive measures

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pre-operative chemotherapy<br> | Drug: cetuximab<br>* cetuximab initial dose 400 mg/m2 iv 1 week before start radiotherapy and subsequent weekly doses of 250 mg/m2 iv for the duration of the radiation treatment<br>* Other names: c225;Radiation: radiotherapy to oesophageal tumour<br>* 45 Gy delivered in 25 fractions of 1.8 Gy 5d/wk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete remission | determination of tumor residual cell content in surgical specimen | 1 month | 
| Resectability rate defined as the number of patients abke to undergo resection after neo-adjuvant treatment |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events during neo-adjuvant treatment as defined by NIH CTCAE v3.0 |  | 5 months | 
| Complications in the post-operative period (defined as 4 weeks after surgery) that can be attributed to surgical procedures |  | 4 weeks | 
| Progression free survival and overall survival |  | 5 years | 
| Define local (locoregional lymphnode metastasis as defined by TNM classification/ malignant peritonitis/ solid masses within the anatomic region of the esophagus) vs distant metastases as first manifestation of recurrence |  | 5 years | 
| The number of R0 resection determined by the pathologist |  | after surgery |