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Targeted radiotherapy to control limited progression in metastatic non-small cell lung cancer

Consolidative Use of Radiotherapy to Block (CURB2) Oligoprogression In Patients With Metastatic Non-Small-Cell Lung Cancer

Phase 3 Interventional Canadian Cancer Trials Group · NCT06686771

This study will try adding focused high-dose radiotherapy (SBRT) to standard immunotherapy or chemo-immunotherapy for people with metastatic non-small cell lung cancer who have a few sites starting to grow (oligoprogression).

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment320 (estimated)
Ages18 Years and up
SexAll
SponsorCanadian Cancer Trials Group Research network
Drugs / interventionschemotherapy, radiation
Locations64 sites (Duarte, California and 63 other locations)
Trial IDNCT06686771 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial compares adding stereotactic body radiotherapy (SBRT) to continuing standard first- or second-line systemic therapy versus the usual approach of changing systemic therapy for patients with oligoprogression during immune checkpoint inhibitor therapy with or without chemotherapy. Eligible participants have stage IV NSCLC without an actionable driver mutation and have shown oligoprogression after at least three cycles of ICI ± chemotherapy, with all progressing sites judged safely treatable by SBRT. Radiation plans must account for prior radiotherapy and available technologies, and patients with treated stable brain metastases may be allowed. The study will track disease control, time to further progression, and safety outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults with stage IV NSCLC without an actionable driver mutation who have a few progressing tumors after at least three cycles of immune checkpoint inhibitor therapy (with or without chemotherapy) and whose progressing sites can be safely treated with SBRT.

Not a fit: Patients with widespread progression, tumors that cannot be safely treated with ablative radiotherapy, or cancers with actionable driver mutations better treated by targeted drugs are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding SBRT could keep cancer controlled longer at progressing sites and delay the need to switch systemic therapies, potentially preserving quality of life.

How similar studies have performed: Smaller randomized and phase II studies and retrospective series in oligometastatic and oligoprogressive NSCLC suggest local ablative radiotherapy can delay progression and extend disease control, but definitive Phase 3 evidence is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Metastatic disease (stage IV) detected on imaging and histologically and/or cytologically confirmed NSCLC as per the WHO Classification of Tumors and AJCC 8th Edition TNM Classification, without a driver mutation with an actionable first-line targeted therapy, for whom either ICI alone or combination ICI + chemotherapy is indicated
* Oligoprogression on first-line ICI +/- chemotherapy systemic therapy after at least 3 cycles.
* All sites of oligoprogression can be safely treated with SBRT or ablative radiotherapy as determined by radiation treatment preplan, including availability and tolerability of necessary technologies (e.g., active breathing control, MRLinac, fiducial insertion, etc.) and accounting for previous radiotherapy overlap. Safety must be assessed and determined by a radiation oncologist.
* Patients with treated CNS disease who have radiologic and clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization).
* Candidate for regulatory approved SOC first-line orsecond-line systemic therapy options.
* Participants must be ≥ 18 years of age.
* ECOG performance status of 0, 1 or 2.
* Participants that received prior adjuvant/neoadjuvant/consolidation systemic therapy (including chemotherapy and ICI ) are eligible if at least 6 months have elapsed between the completion of prior therapy and start of first-line treatment for metastatic disease.
* Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior systemic therapy. If participants experienced prior immune-mediated toxicity and have not yet re-initiated ICI therapy, please contact CCTG. Please also contact CCTG if participants have ongoing toxicity ≥ grade 1 felt to be clinically insignificant.
* Previous surgery related to NSCLC in the curative or metastatic disease setting is permitted. Previous major surgery is permitted provided that surgery occurred at least 28 days prior to participant enrollment and that wound healing has occurred.
* Prior external beam radiation related to NSCLC in the metastatic disease setting is permitted provided a minimum of 14 days (2 weeks) have elapsed between the last dose of radiation and date of enrollment. Patients that received prior external beam radiation therapy in the NSCLC curative disease setting (including the primary lesion) are eligible. Oligoprogressive lesions previously treated with external beam radiation are eligible as long they are clinically asymptomatic, and re-treatment is possible according to the investigator.
* Prior conventional, non-stereotactic radiotherapy for palliative purposes is allowed, and if the palliated lesion subsequently progressed but asymptomatic not requiring immediate RT, the lesion can still be counted toward one of the five oligoprogressive lesions.
* For Arm 1, SBRT must be initiated within 3 weeks of participant enrollment.
* Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in either English, French, or Spanish.
* Reimbursement of continued SOC ICI and chemotherapy systemic therapies may not be uniform across all sites. In the event that site/investigator is unable to provide access to the drug, participant will not be eligible for this trial.
* Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* Participants of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria:

* Large-cell neuroendocrine carcinoma (LCNEC), pulmonary carcinoid tumour or mixed small cell and non-small cell lung cancer are not eligible.
* Presence of leptomeningeal disease.
* Pregnancy.
* Serious medical conditions in which radiotherapy of target lesions is contraindicated (e.g., scleroderma, Ataxia Telangiectasia (ATM), interstitial lung disease (ILD), Child-Pugh C liver function).
* Any other condition in which in the judgement of the investigator would make the patient inappropriate for study entry.
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Concomitant medications should only exclude participants from trial participation when clinically relevant known or predicted drug-drug interactions or potential overlapping toxicities will impact safety or efficacy; please consult the relevant product monographies.
* Concurrent treatment with other anti-cancer therapy, including investigational agents.
* Live attenuated vaccination administered within 30 days prior to enrollment/randomization.

Where this trial is running

Duarte, California and 63 other locations

+14 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-small Cell Lung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.