Induction Chemo-Immunotherapy + Radiotherapy vs Concurrent Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

NCT07559045 | Recruiting Phase 2

• 1 other identifier: KYLL-2025-143
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, phase II clinical study in patients with unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC). Eligible patients will be randomly assigned in a 1:1 ratio to two treatment groups. The experimental group will receive 3 cycles of induction therapy with PD-1 antibody plus chemotherapy, followed by radiotherapy, and then maintenance therapy with PD-1 antibody monotherapy. The control group will receive concurrent chemoradiotherapy, followed by maintenance therapy with PD-1 antibody monotherapy. The primary endpoints are the complete response (CR) rate at 3 months after radiotherapy (assessed by investigators) and the 1-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), quality of life, and safety profile.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Esophageal Squamous Cell Carcinoma; Chemo-Immunotherapy; Induction Therapy; Concurrent Chemoradiotherapy; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) Rate at 3 Months After Radiotherapy (Investigator-Assessed)

  Proportion of patients achieving complete response (CR) per RECIST 1.1, assessed by investigators at 3 months after completion of radiotherapy

  3 months after completion of radiotherapy

• 1-Year Progression-Free Survival (PFS) Rate

  Proportion of patients alive and without disease progression at 1 year after randomization

  1 year after randomization

Secondary Outcomes (9)

• Overall Survival (OS)

  Up to 3 years after randomization

• Progression-Free Survival (PFS)

  Up to 3 years after randomization

• Duration of Response (DOR)

  Up to 3 years after randomization

• Objective Response Rate (ORR)

  Up to 3 years after randomization

• Local Regional Failure-Free Survival (LRFS)

  Up to 3 years after randomization

Study Arms (2)

Experimental Group: Chemo-Immunotherapy Induction + Radiotherapy + PD-1 Maintenance

EXPERIMENTAL

Patients receive 3 cycles of PD-1 antibody plus chemotherapy induction therapy, followed by thoracic radiotherapy (50.4Gy in 28 fractions), then PD-1 antibody maintenance therapy (200mg IV q3w, up to 1 year).

Drug: Paclitaxel plus Cisplatin or Carboplatin (Induction Chemotherapy)

Control Group: Concurrent Chemoradiotherapy + PD-1 Maintenance

ACTIVE COMPARATOR

Patients receive weekly paclitaxel + cisplatin/carboplatin concurrent with thoracic radiotherapy (50.4Gy in 28 fractions), then PD-1 antibody maintenance therapy (200mg IV q3w, up to 1 year).

Drug: Weekly Paclitaxel plus Cisplatin or Carboplatin (Concurrent Chemotherapy)

Interventions

Weekly Paclitaxel plus Cisplatin or Carboplatin (Concurrent Chemotherapy) DRUG

Paclitaxel 50 mg/m² combined with cisplatin 25 mg/m² or carboplatin AUC 5 (maximum 600 mg), administered intravenously once weekly for 5 cycles, concurrent with thoracic radiotherapy (50.4Gy in 28 fractions) for unresectable stage III-IVA esophageal squamous cell carcinoma.

Control Group: Concurrent Chemoradiotherapy + PD-1 Maintenance

Paclitaxel plus Cisplatin or Carboplatin (Induction Chemotherapy) DRUG

Paclitaxel 150-175 mg/m² combined with cisplatin 75 mg/m² or carboplatin AUC 5 (maximum 600 mg), administered intravenously every 3 weeks for 3 cycles, concurrent with PD-1 antibody induction therapy for unresectable stage III-IVA esophageal squamous cell carcinoma.

Experimental Group: Chemo-Immunotherapy Induction + Radiotherapy + PD-1 Maintenance

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate organ function (bone marrow, liver, renal, cardiac) within 2 weeks prior to randomization
• Measurable or evaluable disease per RECIST 1.1
• Willing to provide written informed consent

You may not qualify if:

• Previous radiotherapy to the chest or previous systemic chemotherapy for ESCC
• History of other malignancies within the last 5 years (except cured basal cell carcinoma or cervical carcinoma in situ)
• Severe comorbidities (uncontrolled hypertension, NYHA class III-IV heart failure, active infection, etc.)
• Known hypersensitivity to any study drugs (paclitaxel, cisplatin/carboplatin, PD-1 antibody)
• Pregnant or lactating women
• Participation in another clinical trial within 30 days prior to randomization

Sponsors & Collaborators

• Second Affiliated Hospital of Zunyi Medical University: lead

Study Sites (1)

The Second Affiliated Hospital of Zunyi Medical University, Xinpu New District, Honghuagang District, Zunyi City, Guizhou Province

Zunyi, Guizhou, 563000, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Paclitaxel; Cisplatin; Carboplatin; Induction Chemotherapy

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Drug Therapy; Therapeutics; Remission Induction

Study Officials

• Lei Zhou, Master

  The Second Affiliated Hospital of Zunyi Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian-Guo Zhou, PhD

CONTACT

+86-851-18212154044; jsdxzl@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, parallel-group phase II trial comparing chemo-immunotherapy induction followed by radiotherapy versus concurrent chemoradiotherapy in patients with unresectable stage III-IVA esophageal squamous cell carcinoma.

Study Record Dates

• First Submitted: March 28, 2026
• First Posted: April 30, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)