Chemoradiotherapy in Unresectable Esophageal Cancer

Study Overview
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Brief Summary
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This phase I/II clinical study is designed to evaluate the 1 year local tumor control rate of chemoradiotherapy using albumin-bound paclitaxel and cisplatin in unresectable esophageal squamous cell carcinomas based on Nutritional Risk Screening NRS2002.

Official Title
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A Phase I/II Study of Chemoradiotherapy Using Albumin-Bound Paclitaxel and Cisplatin in Unresectable Esophageal Squamous Cell Carcinomas Based on Nutritional Risk Screening Score (NRS2002)

Conditions
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Esophageal Cancer, Chemoradiotherapy, Albumin-bound Paxlitaxel, Unresectable Malignant Neoplasm

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Albumin-Bound Paclitaxel
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 75 years Pathologically or cytologically proven unresectable esophageal squamous cell carcinomas in patients staged as T3N1M0-1b and T4N0-1M0-1b(AJCC 6th TNM staging,M1b limited to clavicular or celiac lymph node metastasis) Primary treatment performed in Cancer Hospital, Chinese Academy of Medical Sciences ECOG PS score: 0 1 NRS2002 score <3 Estimated survival time ≥3 months Normal organ and marrow function as defined below: Hemoglobin: greater than or equal to 100g/L ;Leukocytes: greater than or equal to 4,000 G/L; Neutrophil: greater than or equal to 2,000 G/L; Platelets: greater than or equal to 100,000/mm3 ; Creatinine: less than or equal to 1.5 times the upper limit or CCR greater than or equal to 60 ml/min; AST/ALT: less than or equal to 2.5 times the upper limit; Total bilirubin: less than or equal to 1.5 times the upper limit; INR: less than or equal to 1.5 times the upper limit; APTT: less than or equal to 1.5 times the upper limit; PT: less than or equal to 1.5 times the upper limit Informed consent Exclusion Criteria: With any distant metastasis out of regional lymphatic drainage or in liver, lung, bone, CNS, etc Patients with other cancer history in 5 years except cervical carcinoma in situ and non-malignant melanoma skin cancer Existing active infection such as active tuberculosis and hepatitis History of myocardial infarction within the past 6 months or history of ventricular arrhythmia Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness History of allergic reactions attributed to paclitaxel, albumin or cisplatin Participation in other clinical trials currently or within 4 weeks of selection Pregnant or lactating females

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: Albumin-Bound Paclitaxel and Cisplatin based chemoradiotherapy<br>Chemoradiotherapy arm receives intensity-modulated radiation therapy, volume modulated arc therapy or tomotherapy concurrently with albumin-bound paclitaxel and cisplatin (weekly intravenous infusion in 5-6 weeks). | Radiation: Radiotherapy<br>* 59.92Gy and 2.14Gy in 28 fractions to PGTV and 50.4Gy and 1.8Gy in 28 fractions 5 days every week in 5.5 weeks.<br>Drug: Albumin-Bound Paclitaxel<br>* 100mg/d weekly,repeatedly on the first day,by intravenous infusion in 5-6 weeks.<br>Drug: Cisplatin<br>* 25mg/m2 weekly,by intravenous infusion in 5-6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control rate | Control rate of primary esophageal cancer and metastatic lymph nodes within irradiation fields | 1 year from the start of treatment to tumor recurrence | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with acute toxicities | Acute toxicities are evaluated by NCI-CTC version 5.0 | 10 week, from the start of treatment to 1 month after chemoradiotherapy | 
| Objective response rate | Objective Response Rate are evaluated by RECIST 1.1 | 5.5 week | 
| Disease Free Survival |  | 1 year, 2 year | 
| Progression Free Survival |  | 1 year, 2 year | 
| Overall Survival |  | 1 year, 2 year | 
| Radiomics analysis | Radiomics analysis for tumor response and survival prediction with pre- and post-chemoradiotherapy based on MRI and CT simulation | 5.5 week | 
| ctDNA analysis | ctDNA analysis to monitor therapeutic efficacy including tumor response and survival outcome | 4 week, 2 month, 1 year, 2 year |