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

Not Applicable

Not yet recruiting

• Conditions: Esophageal Adenocarcinoma; Radiotherapy

• Registration Number: NCT07164690
• Lead Sponsor: Fudan University

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-07-30
• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted QC: 2025-09-09
• Last Update Submitted: 2025-09-09
• Study First Posted: 2025-09-10
• Last Update Posted: 2025-09-10
• Primary Completion: 2026-07
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	1 year

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	1 year
Objective Response Rate (ORR)	1 year
Treatment-related adverse event (TRAE)	1 year