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

First listed
Jun 1, 2018
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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