Pre-op Chemo-RT w/CDDP/5FU vs Chemo w/ Docetaxel/Irinotecan in PET Non Responder Resectable Esophagus Cancer

Study Overview
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Brief Summary
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The purpose of this study is to improve their outcome by either changing the chemotherapy drugs or giving them radiation therapy with concurrent chemotherapy, hoping that this will improve their outcome.

Detailed Description
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This study is aimed at improving the outcome of resectable non PET responders, esophageal carcinoma, by either changing the chemotherapy drugs or giving them radiation therapy with concurrent chemotherapy, hoping that this will improve their outcome.

Official Title
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A Trial Comparing Pre-operative Chemo-radiotherapy With Cisplatin and Fluorouracil Versus Chemotherapy With Docetaxel and Irinotecan in PET Non Responders Resectable Cancer Esophagus: a Multicenter Study

Conditions
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Carcinoma of Esophagus

Intervention / Treatment
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* Drug: irinotecan and docetaxel
* Drug: Cisplatin, fluorouracil and concurrent radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven squamous cell or adenocarcinoma of the thoracic esophagus and gastro-esophageal junction. No distant metastases. Signed written informed consent. Age less than 75 years. Potentially resectable tumor (radiological evidence of resection with no residual disease). ECOG 0 to 2. Normal serum creatinine and adequate hepatic function, serum bilirubin less than 30 mmol/l, serum alkaline phosphatase less than 2 times upper limit of normal and ALT and AST of less than 4 upper limits of normal. Normal bone marrow function with absolute neutrophile count of more than 1500/ml, hemoglobin more than 80 gm/L and platelets more than 100,000 /ml Exclusion Criteria: Serious underlying medical condition which could impair the patient ability to participate in the clinical trial or comply to follow up Prior treatment with other anti cancer therapy or radiation therapy. Legal incapacity. Previous malignancy within 5 years except adequately treated non melanomatous skin cancer or in situ cervical cancer. Psychiatric or mental disorder precluding the understanding of the information of the trial topics and giving valid informed consent.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Arm A: will receive combination of irinotecan and docetaxel regimen for 2 cycles, recycling every 21 days Irinotecan 100 mg/m2 by intra venous infusion over 2 hours in day1 and docetaxel 40 mg/m2 over one hour will be given on day 1 Assessment by PET scan and CT chest and abdomen will be done 2-3 weeks after end of 2nd cycle of irinotecan and docetaxel | Drug: irinotecan and docetaxel<br>* combination of irinotecan and docetaxel regimen for 2 cycles, recycling every 21 days Irinotecan 100 mg/m2 by intra venous infusion over 2 hours in day1 and docetaxel 40 mg/m2 over one hour will be given on day 1 Assessment by PET scan and CT chest and abdomen will be done 2-3 weeks after end of 2nd cycle of irinotecan and docetaxel<br>* Other names: Docetaxel;|
| Experimental: Arm B<br>Arm B will receive combination of cisplatin, fluorouracil and concurrent radiation therapy 50 Gy in 25 fractions over 5 weeks with cisplatin 75 mg/m2 on first day of week 1 and week 5 and fluorouracil 750 mg/m2 daily by continuous intra venous infusion at Day 1 and Day 29 of Radiation therapy for 4 days. PET scan will be repeated 3-4 weeks after end of concurrent chemo-radiation therapy Patients in Arm A and B will go for esophagectomy 4-6 weeks after end of concurrent chemo-radiation therapy or chemotherapy | Drug: Cisplatin, fluorouracil and concurrent radiation therapy<br>* Cisplatin, fluorouracil and concurrent radiation therapy 50 Gy in 25 fractions over 5 weeks with cisplatin 75 mg/m2 on first day of week 1 and week 5 and fluorouracil 750 mg/m2 daily by continuous intra venous infusion at Day 1 and Day 29 of Radiation therapy for 4 days.<br>* Other names: Concurrent RT with CDDP and 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response ( regression score 1a- see response assessment) in each treatment group |  | 5 yrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of conversion from PET non responder to responder with each type of salvage therapy | Failure Free Survival for each treatment group Overall Survival for each treatment group ERCC1 as a predictor of failure of response to cisplatin based chemotherapy in neo adjuvant setting. | 5 yrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized trial,, Pre-operative chemo-RT with CDDP and 5-FU, Multicenter study