Post-operative Radiotherapy After Neodjuvant Chemo-immunotherapy and Surgery in Stage III NSCLC (RESCUE)

Radiotherapy to Optimize Event-free Survival Following Chemo-Immunotherapy and Surgery in Upper Stage III NSCLC With Evidence of Pathological Residual Disease (RESCUE): Phase II Trial

This study investigates whether postoperative radiotherapy (PORT) improves outcomes for patients with stage III non-small cell lung cancer (NSCLC) who have residual disease after neoadjuvant chemo-immunotherapy and surgery. The primary objective is to compare event-free survival (EFS) between patients receiving PORT targeting involved lymph node regions and those without PORT. Secondary and tertiary endpoints include overall survival, locoregional and distant control, toxicity, and quality of life. The phase II randomized trial will enroll 118 patients, stratifying by adjuvant immunotherapy use, with follow-up extending up to 5 years. Statistical analysis aims to detect a 15% improvement in 2-year EFS, with a total study duration of 7 years.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer; Stage III Lung Cancer
• Intervention / Treatment: Radiation: Post-operative radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mom Phat; Phone Number: 514-890-8254; Email: mom.phat.chum@ssss.gouv.qc.ca
• Study Contact Backup: Name: Houda Bahig, MD PhD; Phone Number: 514-890-8254; Email: houda.bahig.med@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4C 3N4
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal
      • Contact: Houda Bahig, MD PhD; Phone Number: 514-890-8254; Email: houda.bahig.med@ssss.gouv.qc.ca
      • Contact: Eva-Sabrina Nkurunziza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be ≥ 18 years old
2. Ability to provide written informed consent
3. ECOG performance status 0-2
4. Histologically confirmed NSCLC
5. Absence of actionable driver mutation (EGFR/ALK/ROS)
6. Complete preoperative imaging staging, including: FDG-PET and brain imaging to exclude distant metastases will be mandatory.
7. Baseline clinical or post-operative pathological stage III including specifically stage T1-4N2-3
8. Completion of 2-4 cycles of neoadjuvant chemo-IO, regardless of the specific immunotherapy and chemotherapy used.
9. Status post-complete (R0) surgical resection with mediastinal lymph node dissection.
10. Residual nodal disease on final pathology specimen (i.e. absence of pathological complete response).
11. Postoperative lung function examination: FEV1 > 1 L (or greater than 35% expected value)

Exclusion Criteria:

1. Pregnant individuals
2. Previous chest radiotherapy
3. >24 weeks after thoracic surgery
4. History of other non-cutaneous neoplasms within the last 24 months
5. Active grade ≥ 2 pneumonitis.
6. Presence of interstitial lung disease
7. Recurrence or metastasis occurred
8. Medical conditions that hinders the safe administration of radiotherapy or follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Post-operative radiotherapy; Mediastinal PORT (40 Gy in 15 fractions) within 24 weeks from thoracic surgery	Radiation: Post-operative radiotherapy; Mediastinal post-operative radiotherapy to a dose of 40 Gy in 15 fractions
No Intervention: No post-operative radiotherapy; No post-operative radiotherapy (PORT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free Survival	Defined as the time from random assignment to loco-regional or distant recurrence, or death from any cause, assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Time from random assignment to death from any cause, assessed up to 60 months.
Grade 3 Toxicity	Classified as early (within the first 3 months) or late (after 3 months), assessed up to 60 months.
Locoregional control	Time from random assignment to locoregional recurrence, proven radiologically and/or pathologically, assessed up to 60 months.
Distant metastasis free survival	Time from random assignment to distant recurrence, proven radiologically and/or pathologically, or death from any cause, assessed up to 60 months.

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2032

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 14, 2025

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 7, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: lung cancer; non small cell lung cancer; Post operative radiotherapy; neoadjuvant immunotherapy; stage III lung cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: RESCUE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD includes anonymized individual participant data collected throughout the course of the study and may include the analyzable data set.
• IPD Sharing Time Frame: study completion date, up to 60 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No