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

NCT06912074 | Recruiting Phase 2

• 1 other identifier: GASTO-10127
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Esophageal Squamous Cell Carcinoma; Hypofractionated Concurrent Chemoradiotherapy; Conventional Fractionated Concurrent Chemoradiotherapy; Induction chemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate

  The proportion of patients who remain free from disease progression during a defined period after treatment initiation.

  2 years

Secondary Outcomes (5)

• Overall survival rate

  2 years

• Clinical response rate

  2 months after radiotherapy

• Rate of grade 3 or higher toxicities

  1 year after therapy

• Distant metastasis-free survival rate

  2 years

• Locoregional recurrence-free survival rate

  2 years

Study Arms (2)

Hypofractionated CCRT group

EXPERIMENTAL

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; Radiation: Hypofractionated Radiation Therapy; Drug: Concurrent Chemotherapy

Conventional fractionated CCRT group

ACTIVE COMPARATOR

Patients in this group will receive a total dose of 5000 cGy in 25 fractions, with 200 cGy per fraction.

Drug: Induction chemoimmunotherapy; Radiation: Conventional Fractionated Radiation Therapy; Drug: Concurrent Chemotherapy

Interventions

Induction chemoimmunotherapy DRUG

All patients will receive two cycles of induction therapy with albumin-bound paclitaxel and cisplatin combined with toripalimab.

Conventional fractionated CCRT group; Hypofractionated CCRT group

Hypofractionated Radiation Therapy RADIATION

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.

Hypofractionated CCRT group

Conventional Fractionated Radiation Therapy RADIATION

Patients will receive a total dose of 5000 cGy in 25 fractions, with 200 cGy per fraction.

Conventional fractionated CCRT group

Concurrent Chemotherapy DRUG

Capecitabine oral administration, 1000 mg/m², twice daily

Conventional fractionated CCRT group; Hypofractionated CCRT group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (12)

• Wang X, Han W, Zhang W, Wang X, Ge X, Lin Y, Zhou H, Hu M, Wang W, Liu K, Lu J, Qie S, Zhang J, Deng W, Wang L, Han C, Li M, Zhang K, Li L, Wang Q, Shi H, Yu Z, Zhao Y, Sun X, Shi Y, Pang Q, Zhou Z, Liang J, Chen D, Feng Q, Bi N, Zhang T, Deng L, Wang W, Liu W, Wang J, Zhai Y, Wang J, Chen W, Chen J, Xiao Z; Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Effectiveness of S-1-Based Chemoradiotherapy in Patients 70 Years and Older With Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2312625. doi: 10.1001/jamanetworkopen.2023.12625.

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MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Hui Liu, Professor

  Sun yat-sen universtiy cancer center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Qiu

CONTACT

+86-020-87343031; qiubo@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: April 4, 2025
• Study Start: April 5, 2025
• Primary Completion (Estimated): April 4, 2029
• Study Completion (Estimated): April 4, 2029
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)