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

Official title

Low-Dose Radiotherapy in Patients With Advanced Esophageal Squamous Cell Carcinoma Resistant to First-Line Chemotherapy Combined With Immunotherapy: a Phase II, Single-arm Study

Overview

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

Interventions

• Radiation Low Dose Radiation Therapy
  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 continu

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: 1 year]

Secondary outcome measures (3)

• Overall Survival (OS) [Time frame: 1 year]
• Objective Response Rate (ORR) [Time frame: 1 year]
• Treatment-related adverse event (TRAE) [Time frame: 1 year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07164690 · 2025-ESOLDRT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗