Fraction Dose Escalation of Split-course Hypofractionated Concurrent Chemoradiotherapy Following Induction Chemo-immunotherapy in Unresectable Locally Advanced Esophageal Squamous Carcinoma: a Phase I Study.

Study Overview
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Brief Summary
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This Phase I study is to determine the maximum tolerated fraction dose (MTD) for split-course hypo-CCRT following induction chemo-immunotherapy in LA-ESCC patients, to clarify the dosimetric advantage of split-course hypo-CCRT, and to investigate the treatment-related toxicities and quality of life of the new regimen.

Detailed Description
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This Phase I study is to determine the maximum tolerated fraction dose (MTD) for split-course hypo-CCRT following induction chemo-immunotherapy in LA-ESCC patients, to clarify the dosimetric advantage of split-course hypo-CCRT, and to investigate the treatment-related toxicities and quality of life of the new regimen.

Official Title
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Fraction Dose Escalation of Split-course Hypofractionated Concurrent Chemoradiotherapy Following Induction Chemo-immunotherapy in Unresectable Locally Advanced Esophageal Squamous Carcinoma: a Phase I Study.

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: Split-course hypo-CCRT
* Drug: Induction chemo-immunotherapy
* Drug: Concurrent chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed ESCC II-IVB stages (IVB stage only with metastatic celiac or supraclavicular lymph nodes) based on the TNM staging system proposed by the International Union Against Cancer (UICC 2002) Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 Charlson Comorbidity Index score≤4 oral medication can be administered despite esophageal obstruction adequate hematological, renal and hepatic functions Exclusion Criteria: contraindication for radiotherapy or chemotherapy prior malignancies, except for curable non-melanoma skin cancer or cervical carcinoma in situ distant metastasis, except for celiac or supraclavicular lymph nodes metastases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Experiment group<br>This is a prospective, single-arm, phase 1 trial. A total of 18 unresectable LA-ESCC patients are required to be enrolled. Induction chemo-immunotherapy All patients receive 2-3 cycles of Abraxane 260mg/m2 d1+cisplatin 60mg/m2 d1+Toripalimab 240mg d1. Hypo-CCRT Evaluation will be performed three weeks after the induction chemo-immunotherapy, LA-ESCC patients without disease progression will continue the split-course hypo-CCRT treatment. Split-course hypo-CCRT is administered at the following three dose levels: Level 1: DT 3000cGy/10 daily fractions/300cGy in the first course, DT 2000cGy/10 daily fractions/200cGy in the second course; Level 2: DT 2800cGy/7 daily fractions/400cGy in the first course, DT 2200cGy/10 daily fractions/220cGy in the second course; Level 3: DT 2500cGy/5 daily fractions/500cGy in the first course, DT 2500cGy10 daily fractions/250cGy in the second course. | Radiation: Split-course hypo-CCRT<br>* Split-course hypo-CCRT is administered at the following three dose levels: Level 1: DT 3000cGy/10 daily fractions/300cGy in the first course, DT 2000cGy/10 daily fractions/200cGy in the second course; Level 2: DT 2800cGy/7 daily fractions/400cGy in the first course, DT 2200cGy/10 daily fractions/220cGy in the second course; Level 3: DT 2500cGy/5 daily fractions/500cGy in the first course, DT 2500cGy10 daily fractions/250cGy in the second course.<br>Drug: Induction chemo-immunotherapy<br>* All patients receive 2-3 cycles of Abraxane 260mg/m2 d1+cisplatin 60mg/m2 d1+Toripalimab 240mg d1.<br>Drug: Concurrent chemotherapy<br>* Concurrent capecitabine was administered orally at 1000mg/m2 twice daily within half an hour after meals concurrently with radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerated fraction dose | Define the maximum tolerated fraction dose (MTD) for split-course hypo-CCRT following induction chemo-immunotherapy. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival rate |  | 2-year | 
| 2-year progression-free survival rate |  | 2-year | 
| Clinical response rate | The percentage of patients who had partial remission or complete remission after therapy | 2 months after radiotherapy | 
| The rate of grade 3 or 4 toxicities according to CTCAE5.0 | the percentage of patients who develop grade 3 or 4 toxicities | 1 year after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Split-course hypofractionated concurrent chemoradiotherapy, Fraction dose escalation, Induction chemo-immunotherapy, Unresectable locally advanced esophageal squamous carcinoma