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NCT07164690

PHASE2

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

Sponsor: Fudan University

View on ClinicalTrials.gov

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

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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2025-09

Completion Date

2027-07

Last Updated

2025-09-10

Healthy Volunteers

Conditions

Esophageal Adenocarcinoma Radiotherapy

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 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.

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.