Combination of Osimertinib and Aspirin to Treat EGFR Mutation NSCLC Patients

NCT04184921 | Completed Phase 2 DMC

• 1 other identifier: COAST 3
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

The third generation epidermal growth factor 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.

Conditions

Lung Cancer Non-small Cell Stage IV

Outcome Measures

Primary Outcomes (1)

• progression-free survival according to resist 1.1

  To evaluate the response to therapy and progression-free survival rate of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

  5 years

Secondary Outcomes (3)

• overall survival（OS）

  5 years

• Objective Response Rate(ORR) according to resist 1.1

  2 years

• Time to progression(TTP) according to resist 1.1

  2 years

Study Arms (2)

osimertinib and aspirin

EXPERIMENTAL

Osimertinib and Aspirin starting at a dose of 80 mg and 100mg 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.

Drug: Aspirin 100mg; Drug: Osimertinib 80 MG

osimertinib

ACTIVE COMPARATOR

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.

Drug: Osimertinib 80 MG

Interventions

Osimertinib 80 MG 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.

osimertinib; osimertinib and aspirin

Aspirin 100mg DRUG

Aspirin, also known as acetylsalicylic acid (ASA), is a very safe medication used to treat pain, fever, or inflammation.

osimertinib and aspirin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced (stage IIIB) or metastatic (stage IV) EGFR-mutant NSCLC. Presence of EGFR-sensitive mutations suitable for treatment with Osimertinib. Intended to receive Osimertinib as first-line therapy, with an expected survival period of more than 3 months.
• At least one measurable tumor lesion that meets the following criteria:
• Not previously irradiated. Accurately measurable. Baseline longest diameter ≥10 mm (for non-lymph node lesions) or short axis ≥15 mm (for lymph node lesions).
• Measurement can be performed via chest CT or PET-CT, provided the method allows reliable repeated measurements.

You may not qualify if:

• Currently receiving other anticoagulant treatments. Patients planning to receive anticancer therapies other than Osimertinib. Presence of contraindications to the use of Osimertinib or Aspirin.

Sponsors & Collaborators

• Daping Hospital and the Research Institute of Surgery of the Third Military Medical University: lead

Study Sites (1)

Daping Hospital

Chongqing, Chongqing Municipality, 400000, China

Location

Related Publications (5)

• Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.

  PMID: 27959700 RESULT

• Shi P, Oh YT, Deng L, Zhang G, Qian G, Zhang S, Ren H, Wu G, Legendre B Jr, Anderson E, Ramalingam SS, Owonikoko TK, Chen M, Sun SY. Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation. Clin Cancer Res. 2017 Nov 1;23(21):6567-6579. doi: 10.1158/1078-0432.CCR-17-1574. Epub 2017 Aug 1.

  PMID: 28765329 RESULT

• Ma J, Cai Z, Wei H, Liu X, Zhao Q, Zhang T. The anti-tumor effect of aspirin: What we know and what we expect. Biomed Pharmacother. 2017 Nov;95:656-661. doi: 10.1016/j.biopha.2017.08.085. Epub 2017 Sep 4.

  PMID: 28881293 RESULT

• Li L, Han R, Xiao H, Lin C, Wang Y, Liu H, Li K, Chen H, Sun F, Yang Z, Jiang J, He Y. Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal. Clin Cancer Res. 2014 May 15;20(10):2714-26. doi: 10.1158/1078-0432.CCR-13-2613. Epub 2014 Mar 18.

  PMID: 24644001 RESULT

• Li S, Dai W, Mo W, Li J, Feng J, Wu L, Liu T, Yu Q, Xu S, Wang W, Lu X, Zhang Q, Chen K, Xia Y, Lu J, Zhou Y, Fan X, Xu L, Guo C. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma. Int J Cancer. 2017 Dec 15;141(12):2571-2584. doi: 10.1002/ijc.31022. Epub 2017 Sep 14.

  PMID: 28857200 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Aspirin; osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: November 29, 2019
• First Posted: December 4, 2019
• Study Start: January 1, 2019
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2024
• Last Updated: February 3, 2026

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)