Hypofractionated vs. Conventional Chemoradiotherapy After Induction Chemo-immunotherapy for Unresectable Esophageal Squamous Cell Carcinoma

November 13, 2025 updated by: Hui Liu, Sun Yat-sen University

Comparing Hypofractionated Concurrent Chemoradiotherapy Versus Conventional Fractionated Concurrent Chemoradiotherapy Following Induction Chemo-immunotherapy in Patients With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective, Open-Label, Randomized Phase II Clinical Trial

This is a prospective, open-label, randomized phase II clinical trial designed to compare the efficacy and toxicity of hypofractionated concurrent chemoradiotherapy versus conventional fractionated concurrent chemoradiotherapy following induction chemoimmunotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, open-label, randomized phase II clinical trial designed to compare the efficacy and toxicity of hypofractionated concurrent chemoradiotherapy versus conventional fractionated concurrent chemoradiotherapy following induction chemoimmunotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma. In this study, patients will receive induction therapy with albumin-bound paclitaxel and cisplatin combined with toripalimab. After induction therapy, they will be randomly assigned to receive either definitive hypofractionated concurrent chemoradiotherapy or conventional fractionated concurrent chemoradiotherapy. Following the completion of treatment, patients will undergo regular follow-up to assess efficacy and safety.

Study Type

Interventional

Enrollment (Estimated)

134

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically or cytologically confirmed diagnosis of esophageal squamous cell carcinoma;
  • Evaluated as unresectable locally advanced esophageal squamous cell carcinoma by endoscopic ultrasound, imaging studies including esophagography, CT of the neck, chest, and upper abdomen, MRI of the neck and chest, whole-body bone scan, or PET/CT, with staging in the range of II-IVB (stage IVB limited to celiac lymph node or supraclavicular lymph node metastasis);
  • Male or female aged 18 to 80 years;
  • Eligible for oral drug therapy;
  • No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy;
  • Tumor sample requirement: Must provide adequate unstained, archived tumor tissue samples for analysis;
  • Expected survival ≥12 weeks;
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1;
  • Postmenopausal women, or women with a negative urine or serum pregnancy test within 14 days before the study drug administration;
  • Women must not be breastfeeding;
  • Organ and bone marrow function must meet the following criteria: Forced expiratory volume in 1 second (FEV1) ≥1000 mL; Absolute neutrophil count ≥1.5 × 10^9/L; Platelets ≥100 × 10^9/L; Hemoglobin ≥90 g/L; Estimated glomerular filtration rate (eGFR) ≥50 mL/min based on the Cockcroft-Gault formula (Cockcroft and Gault, 1976); Serum bilirubin ≤1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
  • Signed and dated informed consent must be provided before participation in any study procedures.

Exclusion Criteria:

Exclusion Criteria for Induction Treatment:

  • Participation in another clinical trial, unless it is an observational (non-interventional) study;
  • Use of immunosuppressive drugs within 28 days prior to the first infusion of Toripalimab, excluding physiological doses of intranasal inhaled corticosteroids, prednisone ≤10 mg/day, or equivalent systemic corticosteroids;
  • Prior use of any anti-PD-1 or anti-PD-L1 antibody;
  • Major surgery within 4 weeks prior to entering the study (excluding vascular access procedures);
  • A history of autoimmune disease within the past 2 years;
  • Active or a history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis);
  • History of primary immunodeficiency;
  • History of organ transplantation requiring immunosuppressive treatment;
  • Uncontrolled complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, active bleeding disorders, including any known HBsAg-positive patients with HBV DNA >500 IU/ml, hepatitis C, or HIV, or any psychiatric or social conditions that would impair the ability to comply with study requirements or harm the patient's ability to provide written informed consent;
  • Receipt of a live attenuated vaccine within 30 days prior to study initiation or within 30 days after receiving Toripalimab;
  • History of another primary malignancy within 5 years prior to the initiation of Toripalimab treatment, excluding adequately treated skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the cervix;
  • Pregnancy, breastfeeding women, or men and women of reproductive potential who are not using effective contraception.

Exclusion Criteria for Concurrent Chemoradiotherapy After Induction Treatment:

  • Development of distant metastasis (excluding celiac lymph node or supraclavicular lymph node metastasis);
  • Development of local regional progression, with the radiation oncologist assessing that the patient cannot receive definitive chemoradiotherapy due to normal tissue dose limitations;
  • PS score of 2-4;
  • Any of the following organ and bone marrow dysfunction criteria: FEV1 <1000 mL; absolute neutrophil count <1.5 × 10^9/L; platelets <100 × 10^9/L; hemoglobin <90 g/L; serum creatinine clearance <50 mL/min according to the Cockcroft-Gault formula (Cockcroft & Gault, 1976); serum bilirubin >1.5 times the upper limit of normal (ULN); ALT and AST >2.5 times ULN.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hypofractionated CCRT group

All patients will receive hypofractionated radiotherapy once daily, five days per week, followed by a boost. Three weeks after the completion of the first phase of hypofractionated radiotherapy, tumor response and cardiopulmonary function will be evaluated. For patients who achieve a partial response, have no deep esophageal ulcers on endoscopy, and have cardiopulmonary function tolerating the radiotherapy boost, a second phase of radiotherapy will be planned using a new CT simulation and radiotherapy design.

First Phase of Radiotherapy: Total dose of 2500 cGy in 5 fractions (500 cGy per fraction). Second Phase of Radiotherapy: Total dose of 2500 cGy in 10 fractions (250 cGy per fraction) The interval between the two phases of radiotherapy will be 28 days.
Drug: Induction chemoimmunotherapy
All patients will receive two cycles of induction therapy with albumin-bound paclitaxel and cisplatin combined with toripalimab.
Radiation: Hypofractionated Radiation Therapy

All patients will receive hypofractionated radiotherapy once daily, five days per week, followed by a boost. Three weeks after the completion of the first phase of hypofractionated radiotherapy, tumor response and cardiopulmonary function will be evaluated. For patients who achieve a partial response, have no deep esophageal ulcers on endoscopy, and have cardiopulmonary function tolerating the radiotherapy boost, a second phase of radiotherapy will be planned using a new CT simulation and radiotherapy design.

First Phase of Radiotherapy: Total dose of 2500 cGy in 5 fractions (500 cGy per fraction) Second Phase of Radiotherapy: Total dose of 2500 cGy in 10 fractions (250 cGy per fraction) The interval between the two phases of radiotherapy will be 28 days.

Drug: Concurrent Chemotherapy
Capecitabine oral administration, 1000 mg/m², twice daily
Active Comparator: Conventional fractionated CCRT group
Patients in this group will receive a total dose of 5000 cGy in 25 fractions, with 200 cGy per fraction.
Drug: Induction chemoimmunotherapy
All patients will receive two cycles of induction therapy with albumin-bound paclitaxel and cisplatin combined with toripalimab.
Drug: Concurrent Chemotherapy
Capecitabine oral administration, 1000 mg/m², twice daily
Radiation: Conventional Fractionated Radiation Therapy
Patients will receive a total dose of 5000 cGy in 25 fractions, with 200 cGy per fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival rate
Time Frame: 2 years
The proportion of patients who remain free from disease progression during a defined period after treatment initiation.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response rate
Time Frame: 2 months after radiotherapy
The percentage of patients who had partial remission or complete remission after therapy
2 months after radiotherapy
Overall survival rate
Time Frame: 2 years
The proportion of patients who are still alive after a specified period of time, regardless of disease progression or relapse.
2 years
Distant metastasis-free survival rate
Time Frame: 2 years
2 years
Locoregional recurrence-free survival rate
Time Frame: 2 years
2 years
Rate of grade 3 or higher toxicities
Time Frame: 1 year after therapy
The percentage of patients who develop grade 3 or higher toxicities. The toxicities are evaluated based on Common Terminology Criteria for Adverse Events version 5.0. The values range from 1 to 5. A higher score means a worse outcome.
1 year after therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Hui Liu, Professor, Sun yat-sen universtiy cancer center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 5, 2025

Primary Completion (Estimated)

April 4, 2029

Study Completion (Estimated)

April 4, 2029

Study Registration Dates

First Submitted

March 28, 2025

First Submitted That Met QC Criteria

March 28, 2025

First Posted (Actual)

April 4, 2025

Study Record Updates

Last Update Posted (Actual)

November 17, 2025

Last Update Submitted That Met QC Criteria

November 13, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GASTO-10127

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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