Stereotactic Radiosurgery + Osimertinib for Lung Cancer with Brain Metastasis

Recruiting at 6 trial locations

Overseen By Helena Yu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: TKIs

Disqualifiers: Leptomeningeal disease, Hematologic malignancy, 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: Unknown

Duration: 3 months

56 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers are doing this study is to find out whether treating brain metastasis with SRS after 3 months of therapy with osimertinib is better than treating with osimertinib alone in people with NSCLC. The researchers will also look at how the study intervention impacts participants' quality of life. The researchers will measure quality of life by having participants complete questionnaires.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves treatment with osimertinib, it's best to discuss your current medications with the study team to ensure there are no interactions.

What data supports the effectiveness of the drug osimertinib for lung cancer with brain metastasis?

Research shows that osimertinib, a drug used for certain types of lung cancer, has good activity in the brain, helping to control cancer that has spread there. Studies suggest that combining osimertinib with radiation therapy may be more effective than using the drug alone for treating brain metastases. ^{1 2 3 4 5}

Is the combination of Stereotactic Radiosurgery and Osimertinib safe for humans?

Osimertinib, used for certain lung cancers, has been associated with side effects like diarrhea, rash, dry skin, and nail issues, with some patients experiencing more severe reactions. Stereotactic Radiosurgery is generally considered safe, but specific safety data for the combination of these treatments is not provided in the available research. ^{4 6 7 8 9}

How is the drug osimertinib unique for treating lung cancer with brain metastasis?

Osimertinib is unique because it is a third-generation drug specifically designed to target certain mutations in lung cancer cells, and it has strong activity in the brain, making it effective for treating brain metastases. When combined with stereotactic radiosurgery, it may offer enhanced control of brain tumors compared to using the drug alone. ^{1 2 3 4 10}

Research Team

Luke Pike, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals with non-small cell lung cancer (NSCLC) that has spread to the brain. Participants should be suitable for stereotactic radiosurgery (SRS), a precise radiation therapy, and able to take osimertinib, a targeted cancer drug.

Inclusion Criteria

I have either not started TKI treatment or began it within the last 3 months.

My lung cancer has a specific EGFR mutation.

I have a brain tumor larger than 1 cm that hasn't been treated with TKI therapy.

Exclusion Criteria

Evidence of leptomeningeal disease on MRI total spine and/or lumbar puncture cytology. The latter are not mandated by protocol but are rather at the discretion of the treating medical team as clinically indicated

My brain cancer has fully responded to treatment.

I have had radiation therapy targeted at my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive osimertinib for 3 months, followed by stereotactic radiosurgery (SRS) for those in the experimental arm

3 months

Follow-up

Participants are monitored for intracranial progression-free survival and quality of life

9 months

Treatment Details

Interventions

• Osimertinib
• Stereotactic Radiosurgery (SRS)

Trial Overview The study compares two approaches: one group receives SRS after 3 months of osimertinib treatment, while the other continues with only osimertinib. The goal is to see if adding SRS improves outcomes and quality of life, which will be assessed through questionnaires.

Participant Groups

Group I: osimertinib and stereotactic radiosurgery (SRS) Experimental Treatment 2 Interventions

Group II: osimertinib alone (standard systemic therapy) Active Control 1 Intervention

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a study of 37 patients with EGFR-mutant non-small cell lung cancer and untreated brain metastases, osimertinib showed a 1-year cumulative incidence of local recurrence in the brain of only 14%, with significantly lower rates (less than 4%) in patients achieving a complete or partial response.

Factors such as uncontrolled primary tumors, a higher number of prior systemic therapies, and worse performance status (ECOG score) were associated with increased risk of local recurrence, indicating that these patients may require closer monitoring and potential additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer. Hui, C., Qu, V., Wang, JY., 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]

In a study of 40 patients with EGFR-mutant non-small cell lung cancer, treatment with osimertinib alone showed similar clinical outcomes to those who received osimertinib combined with cranial irradiation, indicating that radiation may not be necessary for all patients with progressing brain metastases.

The median time to treatment failure, progression-free survival, and overall survival were comparable across groups, suggesting that delaying radiation therapy could reduce toxicity risks for patients who initially respond to osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study. Xie, L., Nagpal, S., Wakelee, HA., et al.[2022]

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 subgroup analysis of 128 patients with non-small-cell lung cancer and CNS metastases, osimertinib showed a confirmed CNS objective response rate of 54% and a disease control rate of 92%, indicating significant efficacy in treating brain metastases.

The safety profile of osimertinib in patients with CNS metastases was consistent with previous studies, suggesting it is a safe option for patients with advanced NSCLC who have progressed after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Goss, G., Tsai, CM., Shepherd, FA., et al.[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]

Osimertinib showed a high overall objective response rate (ORR) of 77% in treatment-naïve patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC), indicating its efficacy as a first-line treatment.

The median progression-free survival (PFS) was approximately 20.5 months across doses, and no acquired EGFR T790M mutations were detected in post-progression samples, suggesting that osimertinib may effectively manage resistance mechanisms in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. Ramalingam, SS., Yang, JC., Lee, CK., 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 (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 a study of 52 treatment-naïve NSCLC patients with brain metastasis and EGFR mutations, the combination of osimertinib and bevacizumab resulted in a high objective response rate of 75% and a median progression-free survival of 17 months.

The treatment was well-tolerated, with manageable side effects such as mild-to-moderate hand-foot syndrome and hypertension, indicating that this combination therapy could be a promising option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib combined with bevacizumab as the first-line treatment in non-small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations. Zhang, L., You, Y., Liu, X., et al.[2023]

References

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

Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer. [2022]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study. [2022]

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

Osimertinib: First Global Approval. [2022]

5. England pubmed.ncbi.nlm.nih.gov

CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. [2022]

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

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

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

Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. [2022]

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

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

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

New Adjuvant Drug for Lung Cancer. [2023]

10. Singapore pubmed.ncbi.nlm.nih.gov

Osimertinib combined with bevacizumab as the first-line treatment in non-small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations. [2023]