TDLN-sparing RT Plus Immunotherapy and Chemotherapy in Locally Advanced ESCC

Tumor Draining Lymph Nodes Sparing Radiotherapy Plus Immunotherapy and Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: a Randomized Phase III Trial

The goal of this clinical trial is to learn if immunotherapy in combination with tumor draining lymph nodes-sparing radiotherapy (TDLN-sparing RT) and chemotherapy works to treat locally advanced esophageal squamous cell cancer in adults.

Researchers will compare immunotherapy in combination with TDLN-sparing RT and chemotherapy to TDLN-sparing RT and chemotherapy to see if immunotherapy works more effectively when using TDLN-sparing RT to treat locally advanced esophageal squamous cell cancer

Participants will:

TDLN-sparing RT for esophageal cancer 50.4Gy/28Fx Paclitaxel plus cisplatin every 3 weeks for 4 cycles PD-1 inhibitors or observation every 3 weeks for 1 year

Study Overview

• Status: Recruiting
• Conditions: Esophageal Carcinoma; Radiotherapy; Immunotherapy
• Intervention / Treatment: Drug: Immunotherapy; Radiation: TDLN-sparing RT; Drug: chemotherapy: Paclitaxel/Cisplatin or other guideline recommended regimens

• Study Type: Interventional
• Enrollment (Estimated): 432
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dashan Zhao; Phone Number: +862164175590; Email: kuaile_z@sina.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhao; Phone Number: +862164175590; Email: kuaile_z@sina.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written informed consent
2. Aged 18-75 years
3. Histologically confirmed esophageal squamous cell carcinoma
4. Clinical stages T2-4N0M0 or TxN+M0 or TxNxM1 (Only for supraclavicular lymph nodes metastasis) based on the 8th UICC-TNM classification

7. Eastern Cooperative Oncology Group(ECOG) performance status: 0-1 8. Life expectancy ≥3 months 9. Adequate organ functions Absolute neutrophil counts (ANC) ≥1.5×109⁄L; Hemoglobin (Hb) ≥9g⁄dl; Platelet (Plt) ≥100×109⁄L; Total bilirubin ≤1.5 upper limit of normal (ULN); Aspartate transaminase (AST) ≤2.5 ULN; Alanine aminotransferase (ALT) ≤2.5 ULN; Creatinine ≤1.5 ULN 10.Received no more than 3 cycles immunotherapy and/or chemotherapy

Exclusion Criteria:

1. Esophageal perforation or hematemesis
2. Any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism and hypothyroidism (effective hormone replacement therapy excepted)) and immunosuppressive agents or systemic hormonal therapy indicated within 28 days (for adverse events of chemoradiotherapy excepted).
3. Allergic to macromolecular protein preparations, or to any of the ingredients in PD-1 inhibitors for injection.
4. Uncontrolled heart diseases or clinical symptoms, such as: (1) New York Heart Association(NYHA) class II or higher heart failure; (2) unstable angina; (3) myocardial infarction within 1 year; (4)clinically significant arrhythmia requiring clinical intervention.
5. Congenital or acquired immunodeficiency (such as HIV infection); active hepatitis B (HBV-DNA≥104 copy number/ml) or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the detection limit of the analytical method); active tuberculosis.
6. Active infection or unexplained fever >38.5 °C within 2 weeks before randomization (fever due to tumor excepted, according to investigator).
7. Patients with fertility reluctant to take contraceptive measures during the trial, or female patients pregnant or breastfeeding.
8. According to the investigator, other factors that may cause termination of the study. ie, other serious diseases (including mental illness) require combined treatment, family or social factors, which may affect the safety or the collection of trial data.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concurrent Immunotherapy plus TDLN-sparing RT and Chemotherapy; PD-1 inhibitors will be administered intravenously, a fixed dose of 200 mg, once every 3 weeks for 1 year. Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles, or other guideline recommended regimens for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx.	Drug: Immunotherapy; PD-1 inhibitors will be administered intravenously, a fixed dose of 200 mg, once every 3 weeks for 1 year.; Radiation: TDLN-sparing RT; TDLN-sparing radiotherapy 50.4Gy/28Fx.; Drug: chemotherapy: Paclitaxel/Cisplatin or other guideline recommended regimens; Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles. or other guideline recommended regimens
Active Comparator: TDLN-sparing RT and Chemotherapy; Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles, or other guideline recommended regimens for 4 cycles. TDLN-sparing radiotherapy 50.4Gy/28Fx. It is allowed to accept immunotherapy followed by radiotherapy.	Radiation: TDLN-sparing RT; TDLN-sparing radiotherapy 50.4Gy/28Fx.; Drug: chemotherapy: Paclitaxel/Cisplatin or other guideline recommended regimens; Paclitaxel 135mg/m2 d1, cisplatin 25mg/m2 d1-3, once every 3 weeks for 4 cycles. or other guideline recommended regimens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PFS for patients with TDLN V15 ≤ 50%	2 years
PFS for all patients	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
OS for patients with TDLN V15 ≤ 50%	2 years
OS for all patients	2 years
Adverse events	up to 2 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 30, 2030

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Biological Therapy; Immunomodulation; Cisplatin; Immunotherapy
• Other Study ID Numbers: ESO-Shanghai 26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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