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

NCT06813664 | Not Yet Recruiting Phase 2

• 1 other identifier: 24-6091
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic NSCLC - Non-Small Cell Lung Cancer; OligoProgressive Metastatic Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Subsequent progression-free-survival

  1 year

• Acute and Late Toxicities

  1 year

• Reported Adverse Events

  1 year

• Quality of Life Outcome

  1 year

• Quality of Life Outcome

  1 year

Study Arms (2)

Decreasing or undetectable ctDNA levels after SBRT/high-dose radiotherapy

EXPERIMENTAL

This group continues the same first-line standard of care or targeted systemic therapy after completion of SBRT.

Radiation: Radiotherapy

Persistent or increasing ctDNA levels after SBRT/high-dose radiotherapy

EXPERIMENTAL

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

Interventions

Radiotherapy RADIATION

SBRT/high-dose radiotherapy Standard of care targeted therapy

Decreasing or undetectable ctDNA levels after SBRT/high-dose radiotherapy

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

C. Jillian Tsai

CONTACT

416-946-4501; jillian.tsai@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: February 7, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

CA (1)