Radiotherapy for Non-Small Cell Lung Cancer

(CURB-TKI Trial)

Overseen By C. Jillian Tsai

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Targeted therapy

Disqualifiers: Pregnant, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of high-dose radiotherapy in treating metastatic non-small cell lung cancer (mNSCLC). Researchers focus on patients whose cancer is driven by specific genetic changes and who have a limited number of progressing cancer lesions, despite targeted therapy. The trial analyzes blood samples to observe changes in cancer DNA levels after radiotherapy, guiding the next treatment steps. Individuals with mNSCLC who can perform most daily activities and have up to five untreated cancer lesions may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from cutting-edge therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study involves targeted therapy, it's possible that you may need to continue certain treatments. Please consult with the trial team for specific guidance.

What prior data suggests that this radiotherapy is safe for non-small cell lung cancer patients?

Research shows that stereotactic body radiation therapy (SBRT) is generally safe for treating non-small cell lung cancer (NSCLC). Studies have found that SBRT is effective and well-tolerated, particularly for early-stage NSCLC, with most patients experiencing no severe side effects.

SBRT has been a breakthrough for treating lung cancer in patients who cannot undergo surgery, such as those with small tumors or those not healthy enough for surgical procedures. While some individuals may experience mild side effects like tiredness or skin irritation, serious complications are rare.

Overall, SBRT has a strong safety record with few harmful side effects, providing confidence in its safety based on these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this approach to treating non-small cell lung cancer because it tailors treatment based on ctDNA levels after radiotherapy. Unlike standard treatments, which don't typically adjust based on real-time molecular changes, this method uses circulating tumor DNA to guide the next steps. For patients with decreasing or undetectable ctDNA levels, continuing the current therapy is possible, potentially reducing unnecessary changes. Meanwhile, those with persistent ctDNA receive a different targeted therapy, aiming to improve outcomes by adapting to the cancer's response. This personalized approach could lead to more effective and timely treatment adjustments.

What evidence suggests that radiotherapy could be an effective treatment for non-small cell lung cancer?

Research has shown that stereotactic body radiation therapy (SBRT) holds promise for non-small cell lung cancer (NSCLC). Studies have found that SBRT effectively controls tumors in patients with early-stage NSCLC, offering long-term survival benefits. It is safe and effective, particularly for patients unable to undergo surgery. SBRT delivers high doses of radiation precisely to the tumor, protecting nearby healthy tissue. This method has revolutionized lung cancer treatment, providing a non-invasive option with positive results. Participants in this trial will receive SBRT/high-dose radiotherapy, with their treatment path determined by ctDNA levels after therapy. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with metastatic non-small cell lung cancer (NSCLC) that have specific genetic changes (EGFR mutation or ALK rearrangement). They can have multiple cancer sites but only up to 5 showing growth. Participants must be able to perform daily activities, complete questionnaires in English, French, or Spanish, and provide blood samples for DNA analysis. Pregnant individuals or those with serious health conditions preventing radiotherapy cannot join.

Inclusion Criteria

My lung cancer has spread and tests show I have EGFR or ALK changes.

My cancer has spread, but I have up to 5 growing spots that don't need immediate treatment.

My cancer can be treated with targeted radiation like SBRT.

Exclusion Criteria

I cannot have radiotherapy due to certain serious health conditions.

Pregnant

My cancer has spread to the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive ablative stereotactic body radiation therapy (SBRT) to oligoprogressive sites

4-6 weeks

Treatment

Participants continue with targeted systemic therapy or switch to a different therapy based on ctDNA levels

Up to 1 year

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Radiotherapy

Trial Overview The trial is testing the effectiveness of targeted stereotactic body radiation therapy (SBRT) on patients whose NSCLC has limited progression while on TKI therapy. It also examines how circulating tumor DNA can guide future targeted treatments after SBRT.

How Is the Trial Designed?

Group I: Persistent or increasing ctDNA levels after SBRT/high-dose radiotherapy Experimental Treatment 1 Intervention

This group of patients will be switched to a different targeted therapy (second line) or standard of care systemic therapy after completion of SBRT.

Group II: Decreasing or undetectable ctDNA levels after SBRT/high-dose radiotherapy Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

In a study of 1361 patients undergoing radiation therapy for locally advanced lung cancer, over half (53%) reported significant declines in their quality of life (QoL) by the end of treatment, indicating that treatment can have a substantial impact on patient well-being.

While clinician-reported adverse events (AEs) were linked to declines in QoL, the correlation was only moderate, suggesting that patient-reported outcomes (PROs) are crucial for understanding the full impact of treatment and may help identify when interventions are needed to improve patient experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Physician- and Patient-Reported Symptoms in Patients Treated With Definitive Radiation Therapy for Locally Advanced Lung Cancer in a Statewide Consortium. Wilkie, JR., Hochstedler, KA., Schipper, MJ., et al.[2022]

Concurrent chemoradiation is the standard treatment for locally advanced unresectable non-small-cell lung cancer, highlighting its efficacy as a major therapeutic option.

New radiotherapy techniques, such as respiratory gating and intensity-modulated radiotherapy, are being developed to improve treatment precision, while stereotactic and proton-beam therapies may offer better options for early-stage tumors in non-operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. Girard, N., Mornex, F.[2009]

In a study of 16,527 non-small cell lung cancer patients, the most common adverse events linked to pharmacotherapy were hypocalcemia, elevated creatine phosphokinase, and hypertriglyceridemia, highlighting the need for monitoring these conditions during treatment.

The modified Apriori algorithm proved to be more effective than the conventional method in identifying associations between chemotherapy drugs and adverse events, suggesting it could be a valuable tool for improving patient safety in cancer pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm. Chen, W., Yang, J., Wang, HL., et al.[2022]

In a study of 63 non-small cell lung cancer (NSCLC) patients receiving immunotherapy, serious immune-related adverse events (irAEs) occurred in a small percentage, including bowel perforations (3.2%) and severe liver issues (3.2%), highlighting the need for careful monitoring during treatment.

While most irAEs are mild and reversible, the occurrence of life-threatening events necessitates a change in treatment strategy, indicating that further clinical trials are essential to better understand and manage these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NSCLC Immunotherapy and Related Rare Toxicities: A Monocentric Real-Life Experience. Divisi, D., De Vico, A., Zaccagna, G., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6318482/

Stereotactic body radiation therapy for non-small cell lung ... This literature review provides an updated analysis of prospective clinical trials evaluating clinical outcomes following SBRT for early stage NSCLC.

2. por-journal.com por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2024.1611709/full

Stereotactic body radiotherapy in lung cancer The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of ...

3. nature.com nature.com/articles/s41598-024-73177-2

Long-term survival and failure patterns in inoperable early- ... This study is to analyse the failure patterns and long-term survival after stereotactic body radiotherapy (SBRT) in patients with T1-3N0M0 inoperable non-small ...

4. ascopubs.org ascopubs.org/doi/10.1200/OP.22.00475

Stereotactic Body Radiotherapy for the Management of ... Having been shown to be safe, effective, and favorable for a vulnerable patient population, SBRT has revolutionized the treatment of early-stage NSCLC.

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-025-02699-4

A prospective outcomes and cost-effective analysis of surgery ... A prospective outcomes and cost-effective analysis of surgery compared to stereotactic body radiation therapy for stage I non-small cell lung ...

6. redjournal.org redjournal.org/article/S0360-3016(24)00480-2/fulltext

Stereotactic Radiation for Ultra-Central Non-Small Cell ... The goals of this study were to determine the maximum tolerated dose (MTD) of SBRT and to assess treatment-related toxicity, oncologic outcomes, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1525730416303746

Stereotactic Body Radiotherapy for Large (> 5 cm) Non– ... Stereotactic body radiotherapy (SBRT) is a well-established treatment option for early stage non–small-cell lung cancer (NSCLC) tumors < 5 cm.