Radiation + TKI Therapy for Lung Cancer

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must be taking: Tyrosine kinase inhibitors

Disqualifiers: Pregnancy, GI absorption issues, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 18 months

34 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have received prior targeted therapy for NSCLC, and you can have had up to 2 cycles of standard chemotherapy before joining the trial.

What data supports the effectiveness of the Radiation + TKI Therapy treatment for lung cancer?

Radiotherapy, including techniques like intensity-modulated radiation therapy (IMRT) and proton-beam therapy, is a major option for treating non-small-cell lung cancer, especially when combined with chemotherapy. These methods aim to maximize treatment benefits while minimizing side effects, and new techniques like stereotactic radiotherapy and proton-beam radiotherapy are being developed for early-stage tumors in non-operable patients. ^{1 2 3 4 5}

Is radiation therapy combined with TKI therapy generally safe for humans?

Advanced radiotherapy techniques like IMRT and IGRT have been used in prostate cancer treatment, showing some risk of gastrointestinal and genitourinary side effects, but they are generally considered safe with careful monitoring. Image-guided radiation therapy (IGRT) has improved safety and accuracy in treatment delivery, making it a common practice in various treatments. ^{3 6 7 8 9}

How is Radiation + TKI Therapy for Lung Cancer different from other treatments?

Radiation + TKI Therapy for Lung Cancer is unique because it combines advanced radiation techniques like intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) with targeted therapy using tyrosine kinase inhibitors (TKIs), which may improve precision and effectiveness in treating non-small cell lung cancer, especially in patients who cannot undergo surgery. ^{1 3 4 10 11}

What is the purpose of this trial?

This prospective, two-part, single-arm, phase II trial is designed to evaluate whether the use of definitive radiation to the primary lung lesion prolongs progression-free survival (PFS) in treatment-naïve, metastatic, driver-mutated non-small cell lung cancers (NSCLC) patients who are subsequently placed on a tyrosine kinase inhibitor (TKI).

Research Team

Jonathan Thompson, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for people with advanced non-small cell lung cancer that hasn't been treated yet. It's specifically for those whose cancer has certain genetic changes (driver mutations) and who are healthy enough to undergo radiation therapy followed by a targeted drug treatment.

Inclusion Criteria

My cancer is at an advanced stage and cannot be treated with a combination of therapies.

I haven't had targeted therapy for NSCLC but may have had up to 2 chemotherapy cycles.

Patient must have measurable disease as defined by RECIST v1.1

Exclusion Criteria

My doctor agrees I can safely receive radiation therapy.

I don't have severe side effects from previous cancer treatments, except for hair loss.

Women must not be pregnant or breast-feeding. All females of childbearing potential must have negative blood or urine pregnancy testing within 14 days of study enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive definitive radiation to the primary lung lesion

1-3 weeks

1-15 visits (in-person)

Treatment

Participants receive a standard-of-care TKI therapy

18 months

Assessments every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Radiation Therapy
• Targeted TKI therapy

Trial Overview The study is testing if giving radiation to the main lung tumor before starting TKI medication can help delay the cancer from getting worse. All participants will receive this sequence of treatments, and their progress will be closely monitored.

Participant Groups

Group I: Radiation therapy followed by mutation-matched TKI treatment Experimental Treatment 2 Interventions

Part 1 will enroll subjects who will be given radiation doses at the discretion of the treating physicians. Subjects with actionable driver mutation will continue to Part 2 and receive a standard-of-care TKI at the discretion of the treating oncologist.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

Patients with non-small-cell lung cancer treated with proton-beam therapy (PBT) experienced significantly less severe symptoms compared to those treated with intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiation therapy (3DCRT), indicating a potential advantage of PBT in minimizing treatment-related side effects.

Among the 82 patients studied, pain related to esophagitis increased more during and decreased more after therapy in the IMRT and 3DCRT groups compared to the PBT group, suggesting that PBT may lead to better symptom management and recovery post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy. Wang, XS., Shi, Q., Williams, LA., et al.[2018]

Different imaging techniques used in lung cancer treatments result in varying radiation doses to patients, with planar and stereoscopic imaging delivering low doses around 1 mGy, while volumetric imaging can range from 10-50 mGy.

Fluoroscopy poses the highest risk, with doses reaching up to 150 mGy, but optimizing imaging protocols can significantly reduce overall patient exposure during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging dose assessment for IGRT in particle beam therapy. Steiner, E., Stock, M., Kostresevic, B., et al.[2018]

In a study involving 18 patients with early-stage central lung tumors, online adaptive intensity modulated proton therapy (IMPT) significantly reduced the mean dose to the bronchial tree compared to MR-guided radiotherapy (MRgRT), suggesting a safer treatment option with lower toxicity risks.

Both non-adaptive and online adaptive IMPT showed significant reductions in the mean doses to the ipsilateral lung and heart compared to MRgRT, indicating improved dose sparing for organs-at-risk during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. Rabe, M., Palacios, MA., van Sörnsen de Koste, JR., et al.[2023]

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]

Combining thoracic radio(chemo)therapy with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) poses a risk of overlapping pulmonary toxicity, making careful patient selection and monitoring essential for optimizing treatment outcomes.

Future strategies should focus on identifying patients who can benefit from this combination therapy while also assessing those at higher risk for severe side effects, using clinical evaluations and biomarkers to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined radiation- and immune checkpoint-inhibitor-induced pneumonitis - The challenge to predict and detect overlapping immune-related adverse effects from evolving laboratory biomarkers and clinical imaging. Guberina, N., Wirsdörfer, F., Stuschke, M., et al.[2023]

In a study of 260 men with localized prostate cancer treated with high-dose IGRT and IMRT, the combination resulted in a low rate of late toxicity, with only 4.4% experiencing grade 2 gastrointestinal issues and 7.1% with grade 2 genitourinary issues after 7 years.

The treatment showed high efficacy, with a 7-year prostate-specific antigen relapse-free survival rate of 97.1% for low-risk patients, indicating that this approach is both safe and effective for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Doležel, M., Odrážka, K., Vaňásek, J., et al.[2021]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

Prostate cancer patients receiving image-guided radiotherapy (IGRT) experienced significantly less severe acute toxicity, such as urinary frequency, diarrhoea, and fatigue, compared to those who did not receive IGRT, with 23% vs 7% for urinary frequency ≥G3 and 15% vs 3% for diarrhoea ≥G2.

The onset of these toxicities was earlier in the non-IGRT group, indicating that IGRT not only reduces the severity of symptoms but also delays their onset, leading to a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Gill, S., Thomas, J., Fox, C., et al.[2021]

In a study of 55 patients with inoperable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiation therapy (IMRT), the 2-year local control rate was 50% for stage I/II patients and 58% for stage III patients, indicating effective disease management.

The treatment was associated with manageable toxicity, with only 11% of patients experiencing grade 3 acute pulmonary toxicity and no acute treatment-related deaths, suggesting that IMRT is a safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience. Sura, S., Gupta, V., Yorke, E., et al.[2022]

Stereotactic body radiotherapy (SBRT) is now the standard treatment for patients with non-small cell lung cancer (NSCLC) who cannot undergo surgery, showing promising results, especially when combined with systemic treatments for oligometastatic cases.

Technological advancements in radiotherapy, such as image-guided techniques and the use of proton and carbon ion therapies, have improved the precision of treatment delivery, leading to better patient outcomes and increased overall survival rates in those with inoperable locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current radiotherapy techniques in NSCLC: challenges and potential solutions. Giaj-Levra, N., Borghetti, P., Bruni, A., et al.[2021]

References

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

Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Imaging dose assessment for IGRT in particle beam therapy. [2018]

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

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. [2023]

4. France pubmed.ncbi.nlm.nih.gov

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

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

Combined radiation- and immune checkpoint-inhibitor-induced pneumonitis - The challenge to predict and detect overlapping immune-related adverse effects from evolving laboratory biomarkers and clinical imaging. [2023]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. [2021]

10. Ireland pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Current radiotherapy techniques in NSCLC: challenges and potential solutions. [2021]