Combination of Osimertinib and Aspirin to Treat 1st Generation EGFR-TKI Resistance in NSCLC

Sponsor
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study ID
NCT03543683
Phase
PHASE2
Status
Completed

Conditions

  • EGFR T790M
  • Non-Small Cell Lung Cancer Stage IIIB
  • Non-small Cell Lung Cancer Stage IV

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Osimertinib — DRUG
    Osimertinib, also known as azd9291, is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. It has been approved in clinical applications by the FDA in 2015.
  • Aspirin — DRUG
    Aspirin, also known as acetylsalicylic acid (ASA), is a very safe medication used to treat pain, fever, or inflammation.

Study Details

The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor（EGFR-TKI） osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

Key Dates

Start date
Jan 1, 2018
Status verified
Jun 2024
Primary completion
Jan 31, 2023
Completion
Jun 1, 2024

Study Design

Enrollment
115 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: osimertinib and aspirin
    Osimertinib starting at a dose of 80 mg once a day, orally with meals.The intervention is aspirin which is starting at a dose of 100 mg once a day, orally with meals.Aspirin treatment will be initiated one week before beginning TKI therapy, if possible, but TKI therapy will not be delayed for Aspirin loading. Drug: Osimertinib and Aspirin will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.
  • Active Comparator: osimertinib
    Osimertinib starting at a dose of 80 mg once a day, orally with meals. Drug: Osimertinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.

Primary Outcome Measure

progression-free survival（PFS） rates according to resist 1.1 [ Time Frame: 3years ]

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