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

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well biologically guided radiation therapy (BgRT) and stereotactic body radiation therapy (SBRT) with osimertinib works for the treatment of EGFR positive non-small cell lung carcinoma that has spread from where it first started (primary site) to a limited number of anatomic sites (oligoprogressive). BgRT is radiation that uses specialized imaging to during treatment to target the active tumor and direct radiation to tumors in order to kill and shrink tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving BgRT with SBRT and osimertinib may kill more tumor cells in patients with oligoprogressive EGFR positive non-small cell lung carcinoma.

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.

What data supports the effectiveness of the drug osimertinib for non-small cell lung cancer?

Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific genetic mutations, particularly the EGFR T790M mutation, as it significantly improved tumor response rates in clinical trials. It was approved by the FDA based on its ability to shrink tumors in patients who had developed resistance to previous treatments. ^{1 2 3 4 5}

Is the combination of BgRT, SBRT, and Osimertinib safe for humans?

Osimertinib, a drug used in this combination, has been generally well tolerated in humans with non-small cell lung cancer, with common side effects including diarrhea, rash, and dry skin. Serious side effects occurred in 28% of patients, and 5.6% stopped treatment due to these effects. No new safety concerns were identified in recent studies. ^{1 2 4 5 6}

What makes the drug osimertinib unique for treating non-small cell lung cancer?

Osimertinib is a unique drug for non-small cell lung cancer because it specifically targets the EGFR T790M mutation, which is often present in patients who have developed resistance to earlier treatments. It is a third-generation drug that works by blocking the signals that help cancer cells grow, and it is taken as a tablet, making it convenient for patients. ^{1 3 5 7 8}

Research Team

Arya Amini

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 (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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. [2022]

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

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

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

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

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

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

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

New Adjuvant Drug for Lung Cancer. [2023]

7. France 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. [2022]

8. England 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. [2022]