AZD9291 for Lung Cancer

(FLAURA Trial)

Recruiting at 149 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Gefitinib, Erlotinib

Must not be taking: CYP3A4 inducers

Disqualifiers: Active malignancy, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: 18 months

674 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications or supplements that strongly affect a liver enzyme called CYP3A4. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug AZD9291 for lung cancer?

Research shows that gefitinib (Iressa) and erlotinib (Tarceva), which are similar to AZD9291, have been effective in treating advanced non-small-cell lung cancer (NSCLC) by targeting specific cancer cell growth pathways. These drugs have shown tumor regression and are approved for use in certain lung cancer treatments. ^{1 2 3 4 5}

What safety data exists for AZD9291 and similar treatments for lung cancer?

Gefitinib (Iressa) and Erlotinib (Tarceva), similar treatments to AZD9291, have been generally well tolerated in patients with advanced lung cancer. Common side effects include diarrhea and rash, but these treatments have been used safely in humans. ^{1 2 4 6 7}

How is the drug AZD9291 different from other lung cancer treatments?

AZD9291, also known as osimertinib, is unique because it specifically targets and inhibits the epidermal growth factor receptor (EGFR) with a mutation that is resistant to other treatments like gefitinib and erlotinib, making it effective for patients with certain types of non-small cell lung cancer (NSCLC) that have developed resistance to first-line EGFR inhibitors. ^{3 4 8 9 10}

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer that can't be treated with surgery or radiation. Participants must have specific EGFR mutations, no prior treatment for metastatic NSCLC, and a good performance status. They should not have severe diseases, uncontrolled heart conditions, or a history of certain lung issues.

Inclusion Criteria

Provision of informed consent prior to any study specific procedures, sampling, and analysis

I can provide a sample of my tumor for EGFR mutation testing.

My lung cancer is confirmed to be adenocarcinoma.

Exclusion Criteria

Your heart's electrical activity (QT interval) is too long when measured on an ECG.

I haven't had extensive radiation to my bone marrow or wide field radiation in the last 4 weeks.

I am not taking any strong CYP3A4 inducers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD9291 or a standard of care EGFR-TKI (gefitinib or erlotinib) as first-line treatment for locally advanced or metastatic NSCLC

18 months

Every 6 weeks for the first 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Every 12 weeks until progression

Open-label extension (optional)

Participants in the Standard of Care arm may opt to receive open-label AZD9291 after disease progression

Treatment Details

Interventions

• AZD9291
• Erlotinib
• Gefitinib

Trial Overview The study tests the effectiveness and safety of AZD9291 compared to standard treatments Erlotinib or Gefitinib in patients with advanced NSCLC. It involves taking either AZD9291 with placebo or one of the standard drugs alone.

Participant Groups

Group I: AZD9291+ placebo Experimental Treatment 3 Interventions

AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150mg or 100mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule.

Group II: Standard of Care + placebo AZD9291 Active Control 3 Interventions

Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

ZD1839 ('Iressa') is a selective inhibitor of the epidermal growth factor receptor that effectively blocks cancer cell growth and survival, showing promising results in preclinical studies with various tumor cell lines and human tumor xenografts.

Preliminary phase I trials indicate that ZD1839 is well-tolerated and shows clinical efficacy, especially in non-small cell lung cancer (NSCLC), leading to its ongoing phase III development for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD1839 ('Iressa') as an anticancer agent. Baselga, J., Averbuch, SD.[2018]

References

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

Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer. [2023]

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

Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. [2023]

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

Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer. [2020]

4. Ireland pubmed.ncbi.nlm.nih.gov

Outcomes of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839, "Iressa") on an expanded access study. [2018]

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

Current knowledge and future directions of the selective epidermal growth factor receptor inhibitors erlotinib (Tarceva) and gefitinib (Iressa). [2022]

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

Erlotinib (Tarceva) for advanced non-small cell lung cancer. [2015]

7. China pubmed.ncbi.nlm.nih.gov

[ZD1839 (Iressa) in the treatment of non-small cell lung cancer patients]. [2011]

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

ZD1839 ('Iressa') as an anticancer agent. [2018]

9. England pubmed.ncbi.nlm.nih.gov

ZD1839 (Iressa): for more than just non-small cell lung cancer. [2019]

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

Successful treatment of multifocal bronchioloalveolar cell carcinoma with ZD1839 (Iressa) in two patients. [2018]