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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining the drug osimertinib with surgery and radiation can more effectively treat advanced non-small cell lung cancer with specific EGFR mutations. Osimertinib aims to halt cancer cell growth, while surgery and radiation directly target and reduce tumors. The trial divides participants into two groups: one receives only osimertinib, and the other receives osimertinib along with surgery and radiation. Ideal participants have advanced non-small cell lung cancer with confirmed EGFR mutations and have not previously received osimertinib or similar drugs. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that osimertinib is generally well-tolerated by patients with non-small cell lung cancer. In one study, about 22% of patients experienced serious side effects. These side effects vary, but only a small number of patients (0.7%) faced a critical issue like interstitial lung disease, which affects the lungs.

When combined with radiation therapy, osimertinib maintains a manageable safety profile. Studies suggest that this combination effectively controls the disease. Patients have demonstrated better outcomes without a significant increase in serious side effects. The medication has been used for some time in treating lung cancer, and its safety is well-documented. Overall, it appears to be a promising and relatively safe option for patients considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Osimertinib is unique because it targets specific mutations in lung cancer cells, specifically EGFR mutations, which are not addressed by many standard treatments like chemotherapy. What sets osimertinib apart is its ability to penetrate the central nervous system, offering potential benefits for patients with brain metastases, a common complication in lung cancer. Additionally, when combined with surgery and radiation, osimertinib may enhance the overall effectiveness of treatment by tackling cancer from multiple angles, potentially leading to better outcomes than traditional methods alone. Researchers are excited because this targeted approach could mean more effective and personalized treatment options for lung cancer patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that osimertinib effectively treats non-small cell lung cancer (NSCLC) with specific EGFR gene changes. Studies have found that patients taking osimertinib experience a longer period before their cancer worsens compared to those on other treatments. In this trial, some participants will receive osimertinib alone, while others will receive it in combination with surgery and/or radiation therapy. Evidence indicates that osimertinib, when used with radiation therapy, is generally well-tolerated and may enhance cancer cells' responsiveness to radiation. Additionally, osimertinib has demonstrated significant survival benefits in different stages of lung cancer. These findings suggest that combining osimertinib with surgery and radiation could be an effective approach to treating this type of lung cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Saumil Gandhi, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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]

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]

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]

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]

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]

Citations

1. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/tagrisso-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years.html

Tagrisso plus chemotherapy demonstrated a median ... Over the past decade, Tagrisso has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung ...

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/TAGRISSO-osimertinib-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years-the-longest-benefit-ever-reported-in-a-global-Phase-III-trial-in-EGFR-mutated-advanced-lung-cancer.html

TAGRISSO® (osimertinib) plus chemotherapy ... TAGRISSO® (osimertinib) plus chemotherapy demonstrated a median overall survival of nearly four years, the longest benefit ever reported in a ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2402614

Osimertinib after Chemoradiotherapy in Stage III EGFR- ... Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S246829422500036X

Real-world comparative outcomes of EGFR-TKIs for first- ... Patients treated with osimertinib had a prolonged time to progression and longer time maintain the treatment compared to 1/2G-TKI. This real-world evidence is ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11304135/

Real-world efficacy of low dose osimertinib as second-line ... Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39576954

A Systematic Review and Single-Arm Meta-Analysis Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33). Conclusion: Osimertinib ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00367-0/fulltext

Osimertinib plus consolidative radiotherapy for advanced ... At a median follow-up of 35.7 months, median PFS was 32.3 months (95% CI, 21.9–51.7), median OS was 45 months (95% CI, 39.3–56.4), and median ...

8. tagrissohcp.com tagrissohcp.com/metastatic/flaura/safety-side-effects.html

Safety Profile of TAGRISSO® (osimertinib) for Metastatic ... There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO- ...