Osimertinib + Surgery + Radiation for Lung Cancer

Recruiting at 3 trial locations

Overseen By Yasir Elamin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inducers

Disqualifiers: CNS metastases, Uncontrolled hypertension, ILD, 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

173 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of osimertinib, surgery, and radiation therapy in patients with advanced lung cancer with specific genetic mutations. It focuses on patients who haven't responded to or have become resistant to previous treatments. The treatment aims to stop cancer cell growth, remove tumors, and eliminate remaining cancer cells. Osimertinib is a medication approved for treating certain types of lung cancer, including those resistant to earlier treatments.

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

The trial requires participants to avoid medications or supplements that strongly affect CYP3A4, an enzyme that processes drugs in the body, at least three weeks before starting the study treatment. If you're taking such medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Osimertinib for lung cancer?

Research shows that Osimertinib significantly prolongs disease-free survival in patients with early-stage, EGFR mutation-positive non-small cell lung cancer (NSCLC) after surgery, as demonstrated in the ADAURA trial. It is effective in treating NSCLC with specific mutations and is generally well tolerated. ^{1 2 3 4 5}

Is the combination of Osimertinib, surgery, and radiation therapy generally safe for humans?

Osimertinib has been studied in patients with lung cancer and is generally well tolerated, with common side effects including diarrhea, rash, dry skin, and nail issues. Serious side effects occurred in about 28% of patients, and a small percentage stopped treatment due to these effects. No new safety concerns were identified in recent studies. ^{1 3 5 6 7}

What makes the drug osimertinib unique for lung cancer treatment?

Osimertinib is unique because it is a third-generation drug specifically designed to target a common mutation (EGFR T790M) in lung cancer that often causes resistance to other treatments, and it can also enhance the effectiveness of radiation therapy. ^{4 5 8 9 10}

Research Team

Saumil Gandhi, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with stage IIIB or IV non-small cell lung cancer that has specific EGFR mutations. They must be in good physical condition, not have had certain previous treatments, and be able to take oral medication. Women of childbearing age must use contraception and not be pregnant or breastfeeding.

Inclusion Criteria

I can swallow pills.

My NSCLC has specific EGFR mutations and I haven't had certain treatments.

You have a tumor that can be measured according to specific guidelines.

Exclusion Criteria

You have had a bad reaction to osimertinib or similar drugs in the past.

Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement

I have brain metastases causing symptoms and affecting my stability.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive osimertinib orally once daily for 6-12 weeks

6-12 weeks

Local Consolidation Therapy (LCT)

Participants undergo surgery and/or radiation therapy daily for 5 consecutive days every week for up to 8 weeks, while continuing osimertinib

Up to 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 6 months

Treatment Details

Interventions

• Osimertinib
• Radiation Therapy
• Therapeutic Conventional Surgery

Trial Overview The NORTHSTAR study is testing the combination of osimertinib (a drug blocking enzymes that promote tumor growth), surgery, and radiation therapy to see if they are more effective together in treating advanced lung cancer with EGFR mutations.

Participant Groups

Group I: Group II (no LCT) Experimental Treatment 1 Intervention

Patients receive osimertinib PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Group I (LCT) Experimental Treatment 3 Interventions

Patients receive osimertinib PO QD for 6-12 weeks. Patients then undergo surgery and/or radiation therapy daily for 5 consecutive days every week for up to 8 weeks. Patients continue osimertinib during and after radiation therapy. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Findings from Research

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

In a phase 3 trial involving 556 patients with advanced non-small-cell lung cancer (NSCLC), osimertinib demonstrated significantly longer progression-free survival (18.9 months) compared to standard EGFR-TKIs (10.2 months), indicating its superior efficacy as a first-line treatment.

Osimertinib also had a similar safety profile to standard EGFR-TKIs but resulted in fewer serious adverse events (34% vs. 45%), making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. Soria, JC., Ohe, Y., Vansteenkiste, J., et al.[2022]

In a study of 94 patients with advanced non-small-cell lung cancer (NSCLC) who had previously been treated, osimertinib showed a 47.3% overall objective response rate and a 90.1% disease control rate, indicating its effectiveness in this population.

Patients with the T790M mutation experienced significantly longer progression-free survival (PFS) compared to those without the mutation, highlighting osimertinib's targeted efficacy, especially in those with specific genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. Mu, Y., Xing, P., Hao, X., 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]

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) 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 (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]

The study established an osimertinib-resistant cell line (HCC827/OSIR) from EGFR-sensitive HCC827 cells, demonstrating that these resistant cells have higher resistance to multiple EGFR tyrosine kinase inhibitors compared to the original cells.

Increased expression of IRE1α was identified as a potential mechanism for resistance to osimertinib, and targeting IRE1α with an inhibitor showed promise in reducing the number of viable resistant cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. Tang, ZH., Su, MX., Guo, X., et al.[2022]

In a phase 2 study involving 210 patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), osimertinib demonstrated significant efficacy, with 70% of patients achieving an objective response, including 3% with complete responses.

Osimertinib was found to have manageable side effects, although serious adverse events occurred in 25% of patients, with interstitial lung disease being the only fatal event possibly related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Goss, G., Tsai, CM., Shepherd, FA., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. [2022]

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

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. [2022]

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

Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. [2022]

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

Osimertinib: First Global Approval. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

New Adjuvant Drug for Lung Cancer. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer. [2022]

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

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. [2022]