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

60 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Radiotherapy for Non-Small Cell Lung Cancer?

Radiotherapy is shown to be effective in controlling tumors in non-small cell lung cancer, especially for patients who cannot undergo surgery. Advances in techniques, like three-dimensional conformal radiotherapy, have improved treatment outcomes by better targeting tumors and minimizing damage to surrounding healthy tissue. ^{1 2 3 4 5}

Is radiotherapy generally safe for treating non-small cell lung cancer?

Radiotherapy for lung cancer can have side effects, including impacts on quality of life and potential cardiac (heart-related) issues, but these vary among patients. It's important to discuss potential risks and monitoring protocols with your healthcare provider. ^{6 7 8 9 10}

How does radiotherapy differ from other treatments for non-small cell lung cancer?

Radiotherapy for non-small cell lung cancer is unique because it can be used in various stages of the disease, especially for patients who cannot undergo surgery. Techniques like three-dimensional conformal radiotherapy and stereotactic body radiotherapy allow for precise targeting of tumors, potentially improving outcomes and reducing side effects compared to traditional methods. ^{1 2 11 12 13}

What is the purpose of this trial?

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The role of radiotherapy and chemotherapy for curative management of medically inoperable and stage III nonsmall cell lung cancer, and radiotherapy for palliation of symptomatic disease. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of radiation therapy on non-small-cell lung cancer. [2020]

3. France pubmed.ncbi.nlm.nih.gov

[Stage IIIB non-small cell lung cancer. Optimization of radiotherapy in lung cancer: some interesting questions to be solved]. [2007]

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Radiotherapy treatment for lung cancer: Current status and future directions. [2021]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm. [2022]

8. Switzerland 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. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer. [2020]

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NSCLC Immunotherapy and Related Rare Toxicities: A Monocentric Real-Life Experience. [2022]

11. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. [2009]

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[Radio-oncologic therapeutic strategy in curative treatment of non-small-cell bronchial carcinoma]. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Hypofractionation in Early Stage Non-Small Cell Lung Cancer. [2022]