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

Efficacy and Safety of Induction Chemo-Immunotherapy Followed by Radiotherapy vs Concurrent Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized, Two-Arm, Phase II Study

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.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Intervention / Treatment: Drug: Paclitaxel plus Cisplatin or Carboplatin (Induction Chemotherapy); Drug: Weekly Paclitaxel plus Cisplatin or Carboplatin (Concurrent Chemotherapy)

Detailed Description

This is a prospective, randomized, two-arm, phase II clinical trial investigating induction chemo-immunotherapy followed by sequential radiotherapy versus concurrent chemo-immunotherapy plus radiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC).

Current standard of care for unresectable locally advanced ESCC is definitive concurrent chemoradiotherapy. However, outcomes remain suboptimal, with high rates of local recurrence and distant metastasis. The addition of PD-1 inhibitors to concurrent chemoradiotherapy has shown promising activity in recent studies, but optimal sequencing and integration of immunotherapy with radiotherapy are still under investigation.

This trial is designed to evaluate whether an induction strategy with chemo-immunotherapy followed by radiotherapy can improve response rates and long-term survival compared to the standard concurrent approach. Patients will be randomized to receive either:

• Experimental arm: Three cycles of induction chemo-immunotherapy, followed by definitive thoracic radiotherapy, then maintenance immunotherapy for up to one year.
• Control arm: Concurrent chemo-immunotherapy plus definitive thoracic radiotherapy, followed by maintenance immunotherapy for up to one year.

The primary objective is to compare the efficacy of the two regimens in terms of complete response and progression-free survival. Safety, tolerability, and quality of life will also be assessed to support the risk-benefit profile of each strategy.

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jian-Guo Zhou, PhD; Phone Number: +86-851-18212154044; Email: jsdxzl@126.com

Study Locations

• China
  • Guizhou
    • Zunyi, Guizhou, China, 563000
      • Recruiting
      • The Second Affiliated Hospital of Zunyi Medical University, Xinpu New District, Honghuagang District, Zunyi City, Guizhou Province
      • Contact: lei zhou, Master; Phone Number: +86-851-18212154044; Email: jsdxzl@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group: Chemo-Immunotherapy Induction + Radiotherapy + PD-1 Maintenance; 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); 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.
Active Comparator: Control Group: Concurrent Chemoradiotherapy + PD-1 Maintenance; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from randomization to death from any cause	Up to 3 years after randomization
Progression-Free Survival (PFS)	Time from randomization to first documented disease progression or death from any cause, whichever occurs first	Up to 3 years after randomization
Duration of Response (DOR)	Time from first documentation of objective response (CR/PR) to first documented disease progression or death	Up to 3 years after randomization
Objective Response Rate (ORR)	Proportion of patients achieving CR or partial response (PR) per RECIST 1.1	Up to 3 years after randomization
Local Regional Failure-Free Survival (LRFS)	Time from randomization to first local or regional recurrence or death	Up to 3 years after randomization
Distant Metastasis-Free Survival (DMFS)	Time from randomization to first distant metastasis or death	Up to 3 years after randomization
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Incidence and severity of TEAEs (graded per CTCAE 5.0) during treatment and follow-up	From first study treatment to 30 days after last treatment
EORTC QLQ-OES18 Symptom Score Change	Change in esophageal cancer-specific symptom score as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oesophageal 18 (EORTC QLQ-OES18) from baseline to post-treatment follow-ups. The scale ranges from 0 to 100, with higher scores indicating more severe symptoms and worse quality of life.	Baseline, 3 months, 6 months, 12 months after radiotherapy
EORTC QLQ-C30 Quality of Life Score Change	Change in quality of life score as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to post-treatment follow-ups. The scale ranges from 0 to 100, with higher scores indicating better quality of life.	Baseline, 3 months, 6 months, 12 months after radiotherapy.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Zunyi Medical University
• Investigators: Principal Investigator: Lei Zhou, Master, The Second Affiliated Hospital of Zunyi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 28, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Esophageal Squamous Cell Carcinoma; Concurrent Chemoradiotherapy; Induction Therapy; PD-1 Inhibitor; Chemo-Immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Organic Chemicals; Therapeutics; Drug Therapy; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Remission Induction; Carboplatin; Paclitaxel; Cisplatin; Induction Chemotherapy
• Other Study ID Numbers: KYLL-2025-143

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