Osimertinib +/− Bevacizumab for Lung Cancer with Brain Metastasis

Recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers

Disqualifiers: Symptomatic brain metastases, Cardiovascular disease, 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: 21

Duration: Up to 2 years

112 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well osimertinib with or without bevacizumab works in treating patients with EGFR positive non-small cell lung cancer that has spread to the brain (brain metastases). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may stop or slow non-small cell lung cancer by blocking the growth of new blood vessels necessary for tumor growth. Giving osimertinib with or without bevacizumab may work better in treating patients with non-small cell lung cancer.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you should avoid medications or supplements that strongly affect CYP3A4 (an enzyme that helps process drugs in the body). It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the drug combination Osimertinib and Bevacizumab for lung cancer with brain metastasis?

Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific mutations, including those with brain metastases, by penetrating the blood-brain barrier and improving survival. Bevacizumab, when combined with other treatments, has been used to enhance the effectiveness of cancer therapies, although its specific role with Osimertinib in brain metastases needs further study. ^{1 2 3 4 5}

Is the combination of Osimertinib and Bevacizumab safe for humans?

Osimertinib has been generally well tolerated in clinical trials for lung cancer, with common side effects including diarrhea, rash, dry skin, and nail issues. Serious side effects occurred in about 28% of patients, leading to treatment discontinuation in 5.6% of cases. No new safety concerns were identified in trials for early-stage lung cancer. ^{1 2 6 7 8}

How is the drug combination of Osimertinib and Bevacizumab unique for treating lung cancer with brain metastasis?

The combination of Osimertinib and Bevacizumab is unique because Osimertinib can effectively penetrate the blood-brain barrier (a protective layer around the brain) and target specific mutations in lung cancer, while Bevacizumab may enhance its effects by inhibiting blood vessel growth in tumors, potentially improving outcomes for patients with brain metastases. ^{3 4 5 9 10}

Research Team

Sarah B. Goldberg

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

This trial is for adults with non-small cell lung cancer that has an EGFR mutation and spread to the brain. They should have a life expectancy over 3 months, be willing to use contraception, and not be breastfeeding or pregnant. No prior EGFR TKI treatment or immunotherapy is allowed, and they mustn't have symptomatic brain metastases or other active cancers.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My lung cancer has a specific change in the EGFR gene.

My cancer can be measured by scans or physical exams, but it's not a must.

Exclusion Criteria

I have had lung conditions that needed steroid treatment.

You are allergic to Chinese hamster ovary cell products or other genetically engineered human antibodies.

I am allergic to osimertinib or similar drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive osimertinib with or without bevacizumab in 21-day cycles, with regular CT scans, MRIs, tumor biopsies, and blood sample collections

Up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevacizumab
• Osimertinib

Trial Overview The study tests if osimertinib alone or combined with bevacizumab is more effective for patients whose lung cancer has spread to the brain. Osimertinib blocks enzymes needed by tumor cells; bevacizumab may prevent tumor growth by inhibiting blood vessel formation.

Participant Groups

Group I: Arm II (osimertinib) Experimental Treatment 1 Intervention

Patients receive osimertinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy and blood sample collection throughout the study.

Group II: Arm I (osimertinib, bevacizumab) Experimental Treatment 6 Interventions

Patients receive osimertinib PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy 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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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 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 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]

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 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, an EGFR inhibitor, shows promise as an effective treatment for patients with untreated non-small cell lung cancer that has spread to the brain.

In clinical studies, osimertinib demonstrated longer median progression-free survival and higher objective response rates compared to older EGFR inhibitors like gefitinib and erlotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib Treats CNS Metastases in NSCLC. [2022]

References

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

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

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

Osimertinib: First Global Approval. [2022]

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

Osimertinib Improves overall survival of EGFR-mutant NSCLC patients with leptomeningeal metastases. [2023]

4. 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]

5. 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]

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

New Adjuvant Drug for Lung Cancer. [2023]

7. France pubmed.ncbi.nlm.nih.gov

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

Osimertinib Treats CNS Metastases in NSCLC. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study. [2022]