ctDNA-Guided CURB for OPD mNSCLC on TKI (CURB-TKI) (CURB-TKI)

Consolidative Use of Radiotherapy to Block Oligoprogression in Patients With Metastatic Non-Small-Cell Lung Cancer on Tyrosine Kinase Inhibitor

This is an open-label, prospective single arm Phase II trial that investigates the role of ablative stereotactic body radiation therapy (SBRT) in oncogene driven metastatic non-small cell lung cancer (mNSCLC) patients with oligoprogressive disease (OPD) on targeted therapy (TKI) followed by circulating tumor DNA (ctDNA) analysis for tailoring targeted therapies.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic NSCLC - Non-Small Cell Lung Cancer; OligoProgressive Metastatic Disease
• Intervention / Treatment: Radiation: Radiotherapy; Radiation: Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: C. Jillian Tsai; Phone Number: 4866 416-946-4501; Email: jillian.tsai@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network
      • Contact: Jillian Tsai; Phone Number: 4866 416-946-4501; Email: jillian.tsai@uhn.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 or older.
2. Able to do most daily activities (ECOG 0-2).
3. Able and willing to sign an informed consent form to join the study.
4. Metastatic non-small cell lung cancer (NSCLC) with either an EGFR mutation or ALK rearrangement confirmed by imaging and biopsy.
5. Eligible for second-line therapy or targeted treatment (TKI) if in Group B.
6. Willing to give a blood sample for ctDNA analysis.
7. No limit to how many metastatic sites, but up to 5 progressive lesions that do not require immediate treatment.
8. Prior radiation therapy near progressive lesions is allowed if applicable.
9. Cancer lesions must be treatable with specific radiotherapy methods (like SBRT or ablative therapy).
10. Oligoprogressive disease is evaluated independently for each lesion using specific criteria.
11. Stable brain metastases allowed if asymptomatic and do not require corticosteroids.
12. Prior treatment with radiation for oligoprogressive lesions is allowed as long as they remain asymptomatic and re-treatment is possible.
13. Prior non-stereotactic radiation for palliative purposes is allowed, and if the lesion later progresses but is still asymptomatic and does not require immediate therapy, it can count towards the 5 oligoprogressive lesions.
14. Able and willing to complete quality of life and health utility questionnaires in English, French, or Spanish.
15. Accessible for treatment and follow-up.

Exclusion Criteria:

1. More than 5 extracranial sites of progressive disease.
2. Pregnant.
3. Leptomeningeal disease.
4. Serious health issues that prevent radiotherapy, like ataxia-telangiectasia or scleroderma.
5. Prior radiation therapy near the progressive lesion that would prevent treatment with SBRT due to exceeding limits of healthy tissue tolerance.
6. Any psychological, social, or geographic issues that could make it difficult to comply with the study.
7. Any other condition that the investigator believes makes participation in the study inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Decreasing or undetectable ctDNA levels after SBRT/high-dose radiotherapy; This group continues the same first-line standard of care or targeted systemic therapy after completion of SBRT.	Radiation: Radiotherapy; SBRT/high-dose radiotherapy Standard of care targeted therapy; Radiation: Radiotherapy; SBRT/high-dose radiotherapy Second-line targeted therapy
Experimental: Persistent or increasing ctDNA levels after SBRT/high-dose radiotherapy; This group of patients will be switched to a different targeted therapy (second line) or standard of care systemic therapy after completion of SBRT.	Radiation: Radiotherapy; SBRT/high-dose radiotherapy Standard of care targeted therapy; Radiation: Radiotherapy; SBRT/high-dose radiotherapy Second-line targeted therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free-survival	Progression-free-survival 1 (PFS1) will be determined from the first day of SBRT to oligoprogressive sites to the day of diagnosis of radiological progression in the subsequent imaging (irrespective of change in systemic therapy in group B, essentially second-line) or death	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subsequent progression-free-survival	Subsequent PFS will be calculated from the date of first radiological progression after SBRT to second radiological progression or change to 3rd line systemic therapy or death or loss to follow-up, whichever comes first.	1 year
Acute and Late Toxicities	For SBRT combined with TKI (using CTCAE Version 5.0)	1 year
Reported Adverse Events	PRO-CTCAE Questionnaire	1 year
Quality of Life Outcome	QLQ-LC13 Questionnaire	1 year
Quality of Life Outcome	EORTC-QLQ-C15 Questionnaire	1 year

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Radiotherapy
• Other Study ID Numbers: 24-6091

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No