Clinical trial NCT06813664: ctDNA-Guided CURB for OPD mNSCLC on TKI (CURB-TKI)
Official title: A Phase II Open-Label Trial: ctDNA-Guided CURB for OPD mNSCLC on TKI (CURB-TKI)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Metastatic NSCLC - Non-Small Cell Lung Cancer
OligoProgressive Metastatic Disease
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2025-02-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free-survival
timeFrame: 1 year
Secondary outcomes:
measure: Subsequent progression-free-survival
timeFrame: 1 year
measure: Acute and Late Toxicities
timeFrame: 1 year
measure: Reported Adverse Events
timeFrame: 1 year
measure: Quality of Life Outcome
timeFrame: 1 year
measure: Quality of Life Outcome
timeFrame: 1 year
measure: Cost-effectiveness
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network
state: Ontario
Study officials:
References: