Radiation + TKI Therapy for Lung Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Jonathan Thompson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Medical College of Wisconsin

Must be taking: Tyrosine kinase inhibitors

Disqualifiers: Pregnancy, GI absorption issues, others

No Placebo Group

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

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).

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}

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.

I am 18 years old or older.

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

Trial 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 (Radiation)
• Targeted TKI therapy (Targeted 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Froedtert Hospital & the Medical College of Wisconsin Milwaukee, WI

Who Is Running the Clinical Trial?

Medical College of Wisconsin Lead Sponsor

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] Intensity-modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT), and proton-beam therapy (PBT) are chemoradiotherapy modalities for treating locally advanced non-small-cell lung cancer. Although therapy is carefully planned to maximize treatment benefit while minimizing risk for adverse side effects, most patients develop radiation-induced symptom burden.

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

Imaging dose assessment for IGRT in particle beam therapy. [2018] Image-guided advanced photon and particle beam treatments are promising options for improving lung treatments. Extensive use of imaging increases the overall patient dose. The aim of this study was to determine the imaging dose for different IGRT solutions used in photon and particle beam therapy.

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] Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking.

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

[Radiotherapy for non-small cell lung cancer]. [2009] Radiotherapy is a major therapeutic option in non small-cell lung cancer. Concurrent chemoradiation is the standard treatment of locally advanced unresectable tumours. Current modalities of thoracic radiotherapy include three-dimensional conformal techniques, allowing dose escalation and combination with new generation cytotoxic drugs to occur. New techniques of radiotherapy are currently under development: respiratory gating and intensity-modulated techniques may allow a better focalisation of the ballistics; stereotactic radiotherapy and proton-beam radiotherapy, less available in Europe at the time, would be indicated in the exclusive treatment of early-stage tumours in non-operable patients.

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] The risk of overlapping pulmonary toxicity induced by thoracic radio(chemo)therapy and immune checkpoint inhibitor therapy in the treatment of patients suffering from non-small cell lung cancer (NSCLC) is one important challenge in successful radioimmunotherapy. In the present opinion we highlight factors that we find important to be considered before treatment initiation, during the treatment sequence, and after treatment completion combined or sequential application of radio(chemo)therapy and immune checkpoint inhibitor therapy. A major aim is to optimize the therapeutic index and to avoid immune related adverse effects. The goals in the future will be focused not only on identifying patients already in the pretreatment phase who could benefit from this complex treatment, but also in identifying patients, who are most likely to have higher grade toxicity. In this respect, proper assessment of clinical performance status, monitoring for the presence of certain comorbidities, evaluation of laboratory parameters such as TGF-α and IL-6 levels, human leukocyte antigens (HLA), and consideration of other potential biomarkers which will evolve in near future are essential. Likewise, the critical parameters must be monitored during the treatment phase and follow-up care to detect potential side effects in time. With the help of high-end imaging which is already used on a daily basis in image guided radiotherapy (IGRT) for intensity modulated radiotherapy (IMRT), its advanced form volumetric modulated arc therapy (VMAT), and adaptive radiation therapy (ART), clinically relevant changes in lung tissue can be detected at an early stage of disease. Concurrent radiotherapy and immunotherapy requires a special focus on adverse events, particularly of the lung, but, when properly approached and applied, it may offer new perspectives for patients with locally advanced NSCLC to be seriously considered as a curative option.

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

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. [2021] The combination of intensity modulated radiation therapy (IMRT) and image guided radiotherapy (IGRT) plays a significant role in sparing normal tissue during prostate cancer treatment. We report the clinical outcomes of 260 patients treated with high-dose IGRT as well as the toxicity of high-dose IGRT in these patients.

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

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021] The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8-5.4, p

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023] This updated report on image guided radiation therapy (IGRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology addressing patient safety. Since the first white papers were published, IGRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The use of IGRT has now extended beyond high-precision treatments, such as stereotactic radiosurgery and stereotactic body radiation therapy, and into routine clinical practice for many treatment techniques and anatomic sites. Therefore, quality and patient safety considerations for these techniques remain an important area of focus.

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

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. [2021] Image-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically.

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] Intensity-modulated radiation therapy (IMRT) is an advanced treatment delivery technique that can improve the therapeutic dose ratio. Its use in the treatment of inoperable non-small cell lung cancer (NSCLC) has not been well studied. This report reviews our experience with IMRT for patients with inoperable NSCLC.

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

Current radiotherapy techniques in NSCLC: challenges and potential solutions. [2021] Introduction: Radiotherapy is an important therapeutic strategy in the management of non-small cell lung cancer (NSCLC). In recent decades, technological implementations and the introduction of image guided radiotherapy (IGRT) have significantly increased the accuracy and tolerability of radiation therapy.Area covered: In this review, we provide an overview of technological opportunities and future prospects in NSCLC management.Expert opinion: Stereotactic body radiotherapy (SBRT) is now considered the standard approach in patients ineligible for surgery, while in operable cases, it is still under debate. Additionally, in combination with systemic treatment, SBRT is an innovative option for managing oligometastatic patients and features encouraging initial results in clinical outcomes. To date, in inoperable locally advanced NSCLC, the radical dose prescription has not changed (60 Gy in 30 fractions), despite the median overall survival progressively increasing. These results arise from technological improvements in precisely hitting target treatment volumes and organ at risk sparing, which are associated with better treatment qualities. Finally, for the management of NSCLC, proton and carbon ion therapies and the recent development of MR-Linac are new, intriguing technological approaches under investigation.