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

Fudan University

Status and phase

Not yet enrolling

Phase 2

Conditions

Radiotherapy

Esophageal Adenocarcinoma

Treatments

Radiation: Low Dose Radiation Therapy

Study type

Interventional

Funder types

Other

Identifiers

NCT07164690

2025-ESOLDRT

Details and patient eligibility

About

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

Enrollment

32 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.