Low-Dose Radiotherapy in Patients With Advanced Esophageal Squamous Cell Carcinoma Resistant to First-Line Chemotherapy Combined With Immunotherapy

NCT07164690 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-ESOLDRT
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

Brief Summary The goal of this single-arm Phase II clinical trial is to learn whether low-dose radiotherapy (LDRT) can restore sensitivity to immunotherapy and prolong disease control in adults with advanced esophageal squamous cell carcinoma who have progressed after first-line chemotherapy combined with PD-1/PD-L1 inhibitors. The main questions it aims to answer are:

• Can LDRT followed by continued immunotherapy increase progression-free survival compared with historical data?
• What is the objective response rate after adding LDRT to ongoing immunotherapy?
• Is LDRT combined with immunotherapy safe in this heavily pre-treated population? Participants will:
• Receive a single fraction of 2 Gy to every visible metastatic lesion within one week
• Continue their prior PD-1/PD-L1 inhibitor (e.g., camrelizumab, pembrolizumab) after LDRT is completed
• Undergo tumor imaging every 6 weeks for up to one year to monitor response
• Provide optional blood and tissue samples for exploratory biomarker studies

Conditions

Esophageal Adenocarcinoma; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  1 year

Secondary Outcomes (3)

• Overall Survival (OS)

  1 year

• Objective Response Rate (ORR)

  1 year

• Treatment-related adverse event (TRAE)

  1 year

Study Arms (1)

LDRT

EXPERIMENTAL

Radiation: Low Dose Radiation Therapy

Interventions

Low Dose Radiation Therapy RADIATION

A dose of 2 Gy/1Fx will be delivered to all currently visible lesions. Lesions in different anatomic sites may be irradiated separately, but the entire course must be completed within one week. * Esophageal primary tumor management: If the investigator judges there is a risk of fistula or bleeding from the esophageal lesion, palliative radiotherapy at 40-50 Gy may be added. * Immunotherapy: The original PD-1/PD-L1 inhibitor regimen will be resumed immediately after LDRT is completed and continued as maintenance therapy. * Chemotherapy: At the investigator's discretion, standard second-line chemotherapy per the current CSCO guidelines for esophageal cancer may be administered.

LDRT

Eligibility Criteria

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

You may qualify if:

• Age≥18 years old;
• ECOG score 0-1;
• Histologically or cytologically confirmed esophageal squamous cell carcinoma that is locally advanced (unresectable) or metastatic (AJCC/TNM 8th edition).
• Progression during or after one prior systemic first-line regimen that contained both a platinum-based chemotherapy and a PD-1/PD-L1 inhibitor (progression must be documented radiologically or clinically). Patients who received neoadjuvant/adjuvant therapy containing a PD-1/PD-L1 inhibitor are considered first-line failures if progression/recurrence occurs during or within 6 months after completion of that therapy.
• At least one measurable lesion per RECIST 1.1 within 4 weeks before enrollment. NOTE: a previously irradiated lesion cannot serve as a target lesion unless clear progression after radiotherapy is documented.
• Life expectancy ≥ 3 months.
• Adequate organ function within 1 week before enrollment:
• Hematologic: Hb ≥ 80 g/L; WBC ≥ 3.0 × 10⁹/L or ANC ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L.
• Hepatic: total bilirubin ≤ 1.5 × ULN (direct bilirubin ≤ ULN if total \> 1.5 × ULN); ALT/AST ≤ 2.5 × ULN.
• Renal: serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min; BUN ≤ 200 mg/L; albumin ≥ 30 g/L.
• Ability to understand and provide written informed consent.

You may not qualify if:

• Active autoimmune disease (e.g., inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, vasculitis).
• Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis.
• Tumor invasion into adjacent organs (aorta or trachea) with high risk of bleeding or fistula; prior esophageal stent placement.
• Other malignancies within the past 2 years (except adequately treated basal-cell carcinoma, cervical carcinoma in situ, etc.).
• Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or uncontrolled arrhythmia.
• Any condition that, in the investigator's opinion, could interfere with study results or increase patient risk.
• Mixed small-cell histology.
• Pregnant or breastfeeding women.
• Congenital or acquired immunodeficiency, HIV infection, prior organ or allogeneic stem-cell transplantation.
• Active HBV, HCV, or tuberculosis infection.
• Prior tumor vaccine or any live vaccine within 4 weeks (inactivated influenza vaccine is allowed).
• Concurrent use of other immunosuppressive agents, chemotherapy, investigational drugs, or chronic corticosteroids.
• Psychiatric illness, substance abuse, or social issues that could compromise compliance.
• Prior intolerance, hypersensitivity, or contraindication to PD-1/PD-L1 inhibitors or chemotherapy components.

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Zhengfei Zhu, PhD

CONTACT

+8618017312901; fuscczzf@163.com

Study Design

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

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: September 10, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share