A Phase II Trial of Induction Chemotherapy With ND-420, Cisplatin and Fluorouracil Followed by Surgery in the Treatment of Patients With Localized Squamous Cell Carcinoma of the Esophagus

Study Overview
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Brief Summary
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Investigator will assign 53 patients who had been histologically proven localized squamous cell carcinoma of esophagus to receive the induction chemotherapy regimen of ND-420 50 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus fluorouracil 700 mg/m2 daily, day1 to day4, every 3 weeks for 2 cycles and then followed by surgical resection. The successful rate of complete treatment per protocol and complete resection will be the primary variant to evaluate in our study.

Official Title
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A Phase II Trial of Induction Chemotherapy With ND-420, Cisplatin and Fluorouracil Followed by Surgery in the Treatment of Patients With Localized Squamous Cell Carcinoma of the Esophagus

Conditions
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Localized Squamous Cell Carcinoma of the Esophagus

Intervention / Treatment
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* Drug: ND-420
* Procedure: Surgery
* Drug: Cisplatin
* Drug: fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have been histologically proven esophageal carcinoma (squamous cell carcinoma). The tumor had to be locally advanced (stage T2-3/N0, T1-3/N+, if technically resectable with curative intent). Patients must be 20 years of age. Patients must have an ECOG performance status score 2. Patients must have a life expectancy of at least 12 weeks. Patients must be accessible for treatment and follow-up at least for one year. Patients must sign the informed consent form. Patient must have:Hemoglobin level 9 g/dl; Neutrophil count 1,500/mm3; Platelets count 100,000/mm3; Serum bilirubin level 1.0 ULN; Serum transaminase (GOT, GPT) levels 2.0 ULN; Serum Alkaline phosphatase levels 2.0 ULN; Serum creatinine level 1.5 mg/dl or Creatinine clearance rate(CrCl)60 ml/min for the institution (calculated by the Cockcroft- Gault equation). Exclusion Criteria: Patient who are receiving or had received concurrent radiotherapy, chemotherapy or other anticancer treatment for esophageal carcinoma. Patients with known history of severe hypersensitivity reactions to any medicine or to drugs formulated with polysorbate 80. Major surgery within two weeks prior to entering the study, excluding port-A insertion or feeding jejunostomy surgery. Patients with CNS metastasis, including clinical suspicion. Patients with clinically detectable peripheral neuropathy 2 on the CTC criteria. Mental statuses of patients are not fit for clinical trial. Fertile men and women unless using a reliable and appropriate contraceptive method. Patients with pregnancy or lactating, women considering pregnancy, possible pregnancy that without using effective contraception. Patients who have serious concomitant illness that might be aggravated by chemotherapy, as below included:Active cardiac disease (e.g. congestive heart failure, angina, arrhythmia, acute myocardial disease or other types of heart disease requiring treatment) within 6 months period preceding entry into the study; Uncontrolled infection (e.g. active infection that uncontrolled for 2 weeks under antibiotic therapy); Retention of body fluid (e.g. pleural effusion, ascites, pericardial effusion, and edema needing treatment); History of other than esophageal cancer, except curatively treated non-melanoma skin cancer or in situ carcinoma of the esophagus; and other conditions which will be judged by physician's discretion.

Ages Eligible for Study
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Minimum Age: 20 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: Induction Chemotherapy DCF followed by Surgery<br>All eligible patients will receive ND-420, Cisplatin and fluorouracil every 3 weeks for 2 cycles. After induction chemotherapy, patients will be planned to receive Surgery. | Drug: ND-420<br>* ND-420 50 mg/m2 on day1<br>* Other names: ND-420(Nangkuang);Procedure: Surgery<br>* After induction chemotherapy, participants will be receive right or left thoracotomy for curative resection by total or subtotal thoracic esophagectomy.<br>Drug: Cisplatin<br>* cisplatin 70 mg/m2 on day1<br>Drug: fluorouracil<br>* fluorouracil 700 mg/m2 daily, day1 to day4<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the R0 resection rate of participants |  | up to three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the response rate (RECIST) of participants |  | up to three months | 
| Number of participants with adverse events as a measure of safety and tolerability |  | up to one year | 
| the population pharmacokinetic parameters (Cmax, AUC... )of ND-420 in the participants |  | 0, 30min, 1hr of ND-420 infusion. selected randomly form one of 3hr, 7hr, 11hr and 23hr after the end of ND-420 infusion. | 
| the correlation between clinical outcomes and the potential predictive genomic biomarkers(B-tubulin mutation, p53-Arg 72Pro, Bcl2-C938A, MDR1-C3435T polymorphism, TNFRSF1B-1466, GSTP1-l105V, CYP1B1, TS-5'UTR) for tumor response |  | up to one year | 
| 1-year survival rate of participants |  | up to one year | 
| pathologic complete response rate of participants |  | up to one year | 
| 1-year progression free survival rate of participants |  | up to one year | 
| 1-year overall survival rate of participants |  | up to one year |