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

Phase 2

Not yet recruiting

• Conditions: Metastatic NSCLC - Non-Small Cell Lung Cancer; OligoProgressive Metastatic Disease

• Registration Number: NCT06813664
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-24
• Study First Submitted QC: 2025-02-03
• Study First Posted: 2025-02-07
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-06
• Study Start: 2025-04-01
• Primary Completion: 2026-04-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Progression-free-survival	1 year	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

Secondary Outcome Measures

Name	Time	Method
Subsequent progression-free-survival	1 year	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.
Acute and Late Toxicities	1 year	For SBRT combined with TKI (using CTCAE Version 5.0)
Reported Adverse Events	1 year	PRO-CTCAE Questionnaire
Quality of Life Outcome	1 year	EORTC-QLQ-C30 Questionnaire
Cost-effectiveness	1 year	EQ-5D-5L Questionnaire

Trial Locations

Locations (1)

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network; 🇨🇦 Toronto, Ontario, Canada