Phase I/II Study of TPF as First-line Chemotherapy in Patients With Metastatic Esophageal Cancer.

Study Overview
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Brief Summary
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A phase I/II study is conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of a combination chemotherapy using docetaxel, cisplatin and 5-fluorouracil (TPF) in untreated patients with metastatic esophageal cancer. The usefulness of the this regimen is evaluated by response rate, median survival time, and progression free survival.

Detailed Description
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Patients with untreated measurable metastatic esophageal cancer were included in this trial. Patients received this combination chemotherapy repeated every 28 days until progression disease. Starting dose (dose level 1) were docetaxel 50 mg/m2 on day 1, fixed dose intravenously cisplatin (15 mg/m2/day) and continuous infusion 5-FU (800 mg/m2/day) on day 1-4. DLT was defined as follows (according to NCI-CTC version 2.0); Grade 4 neutropenia lasting for more than 4days, Grade 4 anemia and thrombocytopenia, Grade 3 neutropenia accompanied fever (>38℃) , and Grade 3 non-hematological toxicity (except for nausea, appetite loss , general fatigue). Maximal Tolerated Dose (MTD) is determined when the incidence of critical toxicity exceeds 50% at a certain dose level. Response rate will be calculated according to RECIST criteria.

Official Title
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Phase I/II Study of Docetaxel, Cisplatin and 5-fluorouracil(TPF) as 1st-line Chemotherapy in Patients With Metastatic Esophageal Cancer.

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: Taxotere
* Drug: 5-FU
* Drug: Briplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or recurrent esophageal tumors with no previous treatment for advanced disease.(Except for small cell carcinoma) At least one measurable lesion according to the RECIST criteria. Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques(Except for Phase I setting). Patients aged between 20 and 75 years, inclusive, at the time of acquisition of informed consent Patients with performance status(ECOG) 0 to 2 Abnormal hematologic values (WBC ≥ 3.0 x 109/L, Hemoglobin ≥ 9.5g/dl, platelet count ≥ 100 x 109/L) Creatinine clearance ≥ 60 ml/min, Serum cleatinine ≤ 1.5mg/dl Serum bilirubin ≤ 1.5mg/dl. ALT, AST ≤ 2.5 x upper normal limit (or ≤ 3 x upper normal limit in the case of liver metastases) Patients who have not received cancer therapy (radiotherapy, chemotherapy or immunotherapy) Life expectancy ≥ 3 months Patients who have given written informed consent to participate in this study Exclusion Criteria: Patients with active multiple cancers; or even if the multiple cancers are metachronous, have a disease-free period of less than 5 years (but excluding cancer in situ and skin cancer) (Except for Phase I setting) Serious, uncontrolled, concurrent infection(s) or illness(es) Patients with no serious concurrent complications (such as heart disease, Intestinal pneumonia) Patients with brain metastasis Patients receiving continuous administration of steroids Patients who have experienced serious drug allergy in the past Patients with retention of body fluid(pleural effusion, ascites, pericardial effusion) necessitating treatment Patients who are pregnant and lactating or hope to become pregnant during the study period Patients with prior Taxan treatment (Paclitaxel, Docetaxel) Patients with edema ≥ grade 2 Others, patients judged by the investigator or subinvestigator to be inappropriate as subject

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Taxotere<br>* X mg/m2, IV (in the vein) on day 1 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: Docetaxel;Drug: 5-FU<br>* 800 mg/m2, CIV (conti.in the vein) on day 1 4 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: 5-Fluorouracil;Drug: Briplatin<br>* 15 mg/m2, IV (in the vein) on day 1 4 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: Cisplatin,CDDP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the DLT(Dose Limiting Toxicity) and MTD(Maximum Tolerated Dose) in Phase I setting. Determine the clinical response rate with Recommended dose in Phase II setting. |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the MST(Median Survival Time) and PFS(Progression Free Survival) in Phase II setting. |  | one year |