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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06020885

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Radiation: Split-course hypo-CCRT Drug: Induction chemo-immunotherapy Drug: Concurrent chemotherapy	Phase 1

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Jan 31, 2024

Anticipated Study Completion Date :

Jul 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experiment group 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 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. Drug: Induction chemo-immunotherapy All patients receive 2-3 cycles of Abraxane 260mg/m2 d1+cisplatin 60mg/m2 d1+Toripalimab 240mg d1. Drug: Concurrent chemotherapy Concurrent capecitabine was administered orally at 1000mg/m2 twice daily within half an hour after meals concurrently with radiotherapy.

Arm

Intervention/Treatment

Experimental: Experiment group

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

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.

Drug: Induction chemo-immunotherapy

All patients receive 2-3 cycles of Abraxane 260mg/m2 d1+cisplatin 60mg/m2 d1+Toripalimab 240mg d1.

Drug: Concurrent chemotherapy

Concurrent capecitabine was administered orally at 1000mg/m2 twice daily within half an hour after meals concurrently with radiotherapy.

Outcome Measures

Primary Outcome Measures

Tolerated fraction dose [6 months]
Define the maximum tolerated fraction dose (MTD) for split-course hypo-CCRT following induction chemo-immunotherapy.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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