Centrally Confined 8Gy/1f to Tumor Core Followed by Concurrent Chemoradiotherapy for Unresectable Stage III NSCLC

NCT07523464 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2026ky476
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, prospective, open-label, single-arm phase I exploratory study designed to evaluate the safety and feasibility of a novel central immune-priming radiotherapy strategy in patients with unresectable stage III non-small cell lung cancer (NSCLC). The investigational approach consists of a single 8 Gy/1 fraction radiotherapy dose delivered to the central subregion of the primary tumor, with rapid dose fall-off to keep the peripheral tumor margin dose below 4 Gy, followed by one cycle of PD-(L)1 inhibitor, and then standard concurrent chemoradiotherapy (cCRT) approximately one week later. Patients without disease progression after cCRT will subsequently receive consolidation immune checkpoint inhibitor therapy. The primary objective is to assess the safety and feasibility of this lead-in immune-priming strategy, particularly whether it can be integrated into standard cCRT and subsequent immunotherapy without unacceptable toxicity or treatment delay. The primary endpoint is the dose-limiting toxicity (DLT) rate, with the DLT observation window defined from initiation of the priming radiotherapy to 6-8 weeks after completion of cCRT. Secondary objectives include the on-time initiation rate of cCRT, cCRT completion rate, initiation rate of consolidation immunotherapy, acute and subacute toxicity profile, preliminary efficacy signals, and dynamic changes in peripheral lymphocyte counts. Exploratory analyses will investigate peripheral immune cell subsets, circulating tumor DNA (ctDNA), T-cell receptor (TCR) clonality, cytokine changes, and their associations with toxicity and clinical outcomes. The study will adopt a safety run-in plus expansion design, with an initial cohort of 6 patients and expansion to 24 patients if safety is acceptable.

Conditions

Radiotherapy; Locally-Advanced Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT) rate

  From the start of priming radiotherapy to 6-8 weeks after completion of cCRT

Study Arms (1)

Centrally Confined 8 Gy/1 Fraction Immune-Priming Radiotherapy to the Tumor Core

EXPERIMENTAL

Centrally Confined 8 Gy/1 Fraction Immune-Priming Radiotherapy to the Tumor Core Followed by Definitive Concurrent Chemoradiotherapy

Radiation: Centrally Confined 8 Gy/1 Fraction Immune-Priming Radiotherapy to the Tumor Core Followed by Definitive Concurrent Chemoradiotherapy

Interventions

Centrally Confined 8 Gy/1 Fraction Immune-Priming Radiotherapy to the Tumor Core Followed by Definitive Concurrent Chemoradiotherapy RADIATION

Centrally Confined 8 Gy/1 Fraction Immune-Priming Radiotherapy to the Tumor Core Followed by Definitive Concurrent Chemoradiotherapy

Centrally Confined 8 Gy/1 Fraction Immune-Priming Radiotherapy to the Tumor Core

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years;
• Histologically or cytologically confirmed NSCLC;
• Unresectable stage III disease according to the AJCC 8th edition;
• Negative for driver gene alterations;
• Considered suitable for definitive cCRT by MDT discussion or investigator judgment;
• ECOG performance status 0-1;
• Presence of a clearly delineable pulmonary primary lesion allowing centrally confined priming treatment planning;
• Adequate major organ function as required by the study;
• Willingness to participate and provision of written informed consent.

You may not qualify if:

• Presence of distant metastasis;
• Positive driver gene alterations;
• Prior definitive thoracic radiotherapy or prior systemic antitumor treatment for the current disease;
• Active autoimmune disease or need for long-term systemic immunosuppressive therapy;
• Active interstitial lung disease, prior severe radiation pneumonitis, or immune-related pneumonitis;
• Special primary tumor location such that safety constraints for centrally confined priming radiotherapy cannot be met;
• Primary lesion immediately adjacent to the main bronchus, carina, major vessels, or esophagus, such that the investigator judges the lead-in intervention to be excessively risky;
• Pregnancy or lactation;
• Any other condition that, in the opinion of the investigator, makes the patient unsuitable for this study.

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

Central Study Contacts

Xiao-yang Li

CONTACT

18701851829; drxyl@ustc.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Participants will receive a single 8 Gy/1 fraction immune-priming irradiation to the central subregion of the pulmonary primary lesion (with edge dose to the primary lesion \<4 Gy), together with one cycle of immune checkpoint inhibitor therapy. Approximately 1 week later, patients will proceed to standard cCRT (60 Gy/30 fractions plus platinum-doublet chemotherapy), followed by sequential immune checkpoint inhibitor consolidation therapy in those without progression.

Study Record Dates

• First Submitted: April 5, 2026
• First Posted: April 13, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share