Study of the Interest of Pursuing or Not the Chemotherapy for Patients With Metastatic Esophageal Cancer

Study Overview
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Brief Summary
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Phase II study, randomized, open-label, multicentric, willing to establish the benefit of pursuing chemotherapy beyond 6 weeks for non progressive patients. The study will proceed in two successive phases : non randomized phase in which all patients will undergo chemotherapy second phase in which only non progressive patients are going to be randomized (discontinuation design). Patients that will show progression in their disease during the first 6 weeks will be released of the study

Detailed Description
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Initial phase: this part of the trial consist of 3 cycles of LV5FU2 (Bolus 5-FU 400mg/m² - 5-FU continuously during 46h: 3000 mg/m², calcium levofolinate 200 mg/m²) - paclitaxel (100 mg/m² at day 1) every 14 days. After 6 weeks,the phase will end with a check-up (clinical exam, tumor evaluation and biological test). Then, if the disease is non-progressive, the patient will proceed to the randomized phase. Randomized phase: Arm A : pursuit of chemotherapy and best supportive care Arm B : interruption of chemotherapy and best supportive care

Official Title
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Phase II Randomized Study Measuring the Interest of Pursuing or Not the CT for Non-progressive Patients With Metastatic Esophageal Squamous-cell Cancer After 6 Weeks of LV5FU2-paclitaxel Given After a 1st Line Fluoropyrimidine/Pt Salt CT

Conditions
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Esophageal Cancer, Squamous Cell

Intervention / Treatment
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* Drug: pursuit of chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suffering from squamous-cell type esophageal cancer histologically proved Metastatic disease measurable according to RECIST criteria. Patients with metachronous metastasis and who have been treated with surgery (+/- radio chemotherapy concurrent or adjuvant chemotherapy) or exclusive radio chemotherapy, are eligible Patients who show progress under chemotherapy that associates a fluoropyrimidine with a platinum salt Man or woman over 18 years old ECOG performance status ≤ 2 Adequate haematological, renal and hepatic functions : PNN ≥ 1500/ mm3; platelets ≥ 100 000/ mm3; Haemoglobin ≥ 9.0 g/dL; ALT and AST ≤ 2.5 ULN (≤ 5.0 in case of liver metastases); Total bilirubin ≤ 1.5 X ULN; Serum creatinine ≤ 1.5 ULN Efficient contraceptive method for both gender (if applicable), during the whole treatment period and the 6 months following the last treatment administration Affiliation to the National Social Security System With informed and signed consent Inclusion Criteria for randomization: ECOG performance status ≤ 2 Able to pursuit the LV5FU2-paclitaxel chemotherapy Non-progressive disease after the initial phase (first tumor exam at week 6) Exclusion Criteria: Patients who received more than one line of chemotherapy for a metastatic disease Presence of other evolutive tumors Cerebral metastasis or other known brain tumors Severe liver failure Pernicious anemia or other anemia due to vitamin B12 defficiency Hypersensibility to an active substance or any other excipients of experimental drugs Every unstable chronicle diseases that can affect patient confidence or security Clinically significant active cardiac disease or myocardial infarction in the 6 previous months Patients with a known dihydropyrimidine dehydrogenase (DPD) deficiency Concomitant treatment with : sorivudin or analogs; prophylactic phenytoin Live attenuated vaccine within the 3 previous months Pregnant or breastfeeding women Unable to comply with the medical monitoring for geographic, social or mental issues Patient Under guardianship or tutorship

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 |
| --- | --- |
| Experimental: Arm A<br>Pursuit of chemotherapy. | Drug: pursuit of chemotherapy<br>* Treatment with LV5FU2 (5-FU, Calcium Levofolinate) - paclitaxel, regular tumor evaluation, best supportive care Other authorized treatment : usual paclitaxel pre-treatment consisting of Dexamethasone, Chlorpheniramine and ranitidine, at 15 and 1 day before the actual paclitaxel treatment<br>* Other names: LV5FU2-paclitaxel CT;|
| No Intervention: Arm B<br>Interruption of chemotherapy, best supportive care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate the overall survival for patients suffering from Esophageal cancer | Non-progressive disease at and after 6 weeks of treatment until progression | From date of randomization until the date of death from any cause, up to 8 months after the beginning of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate efficiency in term of overall survival, of pursuing chemotherapy | beyond 6 weeks of treatment compared to a group that interrupted the treatment at 6 weeks | From date of randomization until the date of death from any cause, up to 8 months after the beginning of the treatment | 
| Estimate the efficiency in term of progression-free of pursuing chemotherapy | beyond 6 weeks of treatment | From date of randomization until the date of first documented progression or date of death from any cause, up to 8 months after the beginning of the treatment | 
| Estimate the rate of non progressive patients | after the 6 firsts weeks of treatment | From date of inclusion until the date of the end the 6 firsts weeks of treatment | 
| Estimate the overall survival of the whole study population | beyond the inclusion | From date of inclusion until the date of death from any cause, up to 8 months after the beginning of the treatment | 
| Measure the toxicity of chemotherapy | during the initial treatment phase compared to the 2 treatment arms after randomization | from baseline up to 12 months | 
| Estimate the consequences of pursuing chemotherapy | beyond 6 weeks of treatment in term of time until degradation of life quality and in term of overall benefits | From date of randomization until the date of first documented progression or date of death from any cause, up to 8 months after the beginning of the treatment |