Efficacy and Safety of TPF Induction Chemotherapy for Borderline-resectable Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This trial studies the efficacy and safty of paclitaxel in combination with cisplatin and 5-fluorouracil(TPF) induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma.

Detailed Description
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Esophageal cancer is one of the most common malignant tumors in China. In Asian countries, esophageal squamous carcinoma is the main pathological type of esophageal carcinoma. Prognosis of esophageal squamous carcinoma is usually poor and surgery is the only radical treatment. However, the optimal therapy pattern for local advanced esophageal carcinoma is still unclear. Part of the patients that clinical staging as T4 and with bulky lymph node metastasis are initially diagnosed as borderline-resectable, which means patients may be able to undergo R0 resection. However, for patients who are diagnosed as borderline-resectable esophageal carcinoma, there are still no sufficient studies implicate that how to improve R0 resection rate by convertion chemotherapy. Cisplatin in combination with 5-FU and docetaxel regimen(DCF) was reported as effective neoadjuvant chemotherapy in treating esophageal squamous carcinoma. However, studies also showed that the DCF regimen caused severe adverse reaction. The mechanism of paclitaxel is similar to docetaxel while with less adverse events than docetaxel. Based on the research situation mentioned above, the investigators decided to conduct a phase II clinical trial to further explore the efficacy and safety of paclitaxel in combination with cisplatin and 5-FU (TPF) induction chemotherapy for locally advanced borderline-resectable esophageal squamous carcinoma.

Official Title
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Paclitaxel In Combination With Cisplatin and 5-fluorouracil(TPF) Induction Chemotherapy for Locally Advanced Borderline-resectable Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Paclitaxel+Cisplatin+5fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients should be voluntary to the trial and provide with signed informed consent. Male or female patients, age:18-70 years old Confirmed by histology of thoracic esophageal squamous cell carcinoma without metastasis and diagnosed as boundary resectable by Multidisciplinary consultation, including cT4 and/or bulky lymphadenopathy that may invade nearby organs(such as the great vessels, trachea and heart, etc.) Measurable or unmeasurable lesions according the RECIST 1.1 criteria. No previous chemotherapy or radiotherapy. Life expectancy ≥ 3 months. ECOG PS 0-1. Blood routine within 7 days：Hb ≥9g/L，NE ≥1.5×109/L，PLT ≥100×109/L； Hepatic and renal function：TB <1.5 UNL， Cr< 1.5× UNL， AST / ALT < 2.5× UNL， ALP < 5.0 × UNL。 No severe complications such as active digestive tract hemorrhage, perforation, jaundice, gastrointestinal obstruction, non-cancerous fever > 38 ℃ Fertile patients should take effective contraceptive measures. Patients should have good compliance and cooperate with the evaluation of efficacy and adverse events and follow-ups according to the research plan. Exclusion Criteria: Cervical esophageal carcinoma. Known severe hypersensitivity to drugs in the regimen. Patient has a concurrent malignancy or has a malignancy within 5 years of study enrollment(with the exception of nonmelanoma skin cancer or cervical carcinoma in situ). Evidence of serious heart disease, including recorded history of congestive heart-failure, uncontrolled serious arrhythmia, angina that needs treatment of drugs, clinical diagnosed cardiac valve disease, history of serious myocardial infarction and intractable hypertension. Evidence of chronic diarrhea(≥4 times/day) or renal dysfunction. Evidence of active infection or active epidemic disease. Psychiatric illness that would prevent the patient from giving informed consent Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel+Cisplatin+5fluorouracil<br>Patients will receive the following chemotherapy: Paclitaxel 135mg/m2 IV over 3 hours on Day 1; Cisplatin 75mg/m2 IV over 1 hours on Day 1; 5-FU 4g/m2 for 5 days continuous infusion from Day 1 to Day 5. | Drug: Paclitaxel+Cisplatin+5fluorouracil<br>* Patients will receive the following chemotherapy: Paclitaxel 135mg/m2 IV over 3 hours on Day 1; Cisplatin 75mg/m2 IV over 1 hours on Day 1; 5-FU 4g/m2 for 5 days continuous infusion from Day 1 to Day 5.<br>* Other names: 5fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | The rate of R0 resection | following resection for up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response rate | The rate of pathologic complete response following surgery | following resection for up to 36 months | 
| OS | the duration from enrollment to the patient's death (all causes) | for up to 36 months | 
| PFS | the duration from enrollment to tumour progression or the patient's death (all causes) (whichever comes first) | for up to 36 months | 
| Adverse envents | Incidence of AEs and SAEs during the study. | for up to 12 months |