BgRT + SBRT + Osimertinib for Non-Small Cell Lung Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Osimertinib

Must not be taking: Antiarrhythmics, QT prolonging drugs

Disqualifiers: Uncontrolled illness, Active infection, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 2 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of advanced radiation therapies and osimertinib, a targeted therapy drug, to treat EGFR positive non-small cell lung cancer that has spread to a few other parts of the body. The trial employs targeted radiation to destroy cancer cells while preserving healthy tissue and uses a drug that blocks a protein aiding cancer growth. Individuals with this type of lung cancer, whose disease has progressed after initial osimertinib treatment, might be suitable candidates for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as chemotherapy, radiation therapy, biological therapy, immunotherapy, strong CYP3A4 inducers/inhibitors, class 1A or class III antiarrhythmic agents, and drugs known to prolong the QT interval, within a specified period before starting the trial. However, you can continue taking osimertinib.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that osimertinib is generally safe for people with advanced non-small cell lung cancer (NSCLC) with the EGFR mutation. Most side effects are mild and easily managed. Common side effects include skin rash and diarrhea, but these are usually not severe.

Stereotactic body radiation therapy (SBRT) effectively treats non-small cell lung cancer. Studies indicate it controls tumor growth well and is usually well-tolerated by patients. While some risks of side effects exist, they are often manageable.

Biologically guided radiation therapy (BgRT) is a newer method, and detailed safety data remains limited. However, it aims to be precise by targeting only active tumor cells, potentially leading to fewer side effects.

Overall, both osimertinib and SBRT have shown good safety profiles. While BgRT is still under study, it is designed to minimize harm to healthy tissue. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for non-small cell lung cancer because it integrates innovative radiation techniques with a targeted therapy. Unlike standard treatments that often rely solely on chemotherapy or radiation, this approach uses BgRT (Biologically Guided Radiotherapy) and SBRT (Stereotactic Body Radiotherapy) alongside osimertinib, a targeted therapy known for its effectiveness against specific genetic mutations. BgRT and SBRT allow for precise targeting of tumors, potentially reducing damage to healthy tissues and enhancing treatment effectiveness. Osimertinib specifically targets and inhibits the EGFR mutation, which is a common driver of cancer growth in certain lung cancer patients. This combination offers a more personalized treatment strategy, aiming to improve outcomes and reduce side effects compared to traditional approaches.

What evidence suggests that BgRT, SBRT, and osimertinib could be effective for non-small cell lung cancer?

Research has shown that osimertinib, which participants in this trial will receive, effectively treats non-small cell lung cancer (NSCLC), particularly in patients with specific genetic changes called EGFR mutations. Studies have found that it helps patients live longer and is generally well-tolerated. In this trial, participants will also undergo radiation treatments, including biologically guided radiation therapy (BgRT) and stereotactic body radiation therapy (SBRT). BgRT uses special imaging to focus on active tumors, while SBRT delivers high-dose radiation precisely, reducing damage to healthy tissue. Together, these treatments offer promising results for controlling and reducing the spread of tumors in NSCLC. ^{5 6 7 8 9}

Who Is on the Research Team?

Arya Amini

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer (NSCLC) that has spread to a few sites and have been stable on osimertinib for over 6 months. They must be able to take oral meds, have a life expectancy of at least 6 months, and agree to birth control measures. Excluded are those with certain heart conditions, untreated brain metastases, significant illnesses, or taking drugs that affect the study medication.

Inclusion Criteria

I have only been treated with osimertinib for my advanced disease.

I can perform daily activities with minimal assistance.

My tumor has a specific EGFR mutation known to respond to certain treatments.

Exclusion Criteria

I haven't taken strong CYP3A4 drugs in the last 14 days.

I have a history of HIV or hepatitis B/C.

I had cancer before, but it was either treated over 5 years ago, was a low-risk type, or was skin/cervical cancer not spreading.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive osimertinib daily and undergo BgRT/SBRT every other day for 5 treatments

2 weeks

5 visits (in-person) for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at 1 week, 3 months, 6 months, and 12 months

12 months

4 visits (in-person)

Extension

Participants may receive additional BgRT/SBRT therapy if progression is found, and continue osimertinib in the absence of > 5 sites of progression or unacceptable toxicity

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Biologically Guided Radiation Therapy (BgRT)
• Osimertinib
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The trial tests biologically guided radiation therapy (BgRT) combined with stereotactic body radiation therapy (SBRT) and osimertinib in patients whose NSCLC has progressed in limited areas. BgRT targets active tumors during treatment while SBRT delivers precise high-dose radiation to minimize damage to healthy tissue.

How Is the Trial Designed?

Group I: Treatment (BgRT/SBRT) Experimental Treatment 6 Interventions

Patients continue to receive osimertinib PO QD in the absence of unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients then continue to receive osimertinib and are monitored via imaging. If additional progression is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the absence of \> 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib for more than 4 weeks. Patients undergo CT scan or PET/CT scan and blood sample collection throughout the study.

Osimertinib is already approved in United States, European Union for the following indications:

Approved in United States as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Approved in European Union as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In vitro studies identified the BRAF G469A mutation as a key mechanism of acquired resistance to osimertinib in non-small cell lung cancer cells, indicating that this mutation allows cancer cells to continue growing despite treatment.

Treatment with selumetinib and trametinib was effective in restoring sensitivity to osimertinib and increasing cell death in resistant clones, suggesting potential strategies to overcome resistance in patients with this mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion. La Monica, S., Minari, R., Cretella, D., et al.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

In a study of 61 advanced non-small-cell lung cancer patients with brain metastases, osimertinib combined with cranial radiotherapy did not show a significant improvement in overall response rates or progression-free survival compared to osimertinib alone.

However, patients with the L858R mutation experienced a longer overall survival with the combination treatment, while those with exon 19 deletions had better outcomes with osimertinib alone, indicating that the effectiveness of treatment may vary based on specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of osimertinib plus cranial radiotherapy compared to osimertinib alone in NSCLC patients with EGFR-activating mutations and brain metastases: a retrospective study. Zhai, X., Li, W., Li, J., et al.[2022]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

Citations

1. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.921473/full

The potential of biology-guided radiation therapy in ... We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301616331480

The Effect of Biologically Effective Dose and Radiation ... To determine the effect of biologically effective dose (BED10) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small ...

3. 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 ...

4. redjournal.org redjournal.org/article/S0360-3016(10)03241-4/fulltext

Higher Biologically Effective Dose of Radiotherapy Is ... A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival.

5. ccts.amegroups.org ccts.amegroups.org/article/view/52566/html

Advances in stereotactic body radiation therapy for early stage ... Stereotactic body radiation therapy (SBRT) has emerged as an effective, non-invasive treatment option for patients with medically inoperable NSCLC.

6. astro.org astro.org/meetings-and-education/micro-sites/2024/annual-meeting/daily-news/tuesday/abstract-191

Biologically Guided Radiation Therapy: Our Field's Answer ... ... non-small cell lung cancer ... Safety data was not provided in the abstract. Presently, there are a number of studies that have attempted to incorporate ...

7. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00193-9/fulltext

Safety and Efficacy of Stereotactic Magnetic Resonance ... For patients with non-small-cell lung cancer (NSCLC), stereotactic ablative body radiation therapy (SABR) is a standard of care for patients ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05830058

Positron Emission Tomography (PET) Guided Stereotactic ... This phase II trial tests the safety of positron emission tomography (PET) guided stereotactic body radiation therapy (SBRT) and how well it works to treat ...

9. 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, ...