SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03543683

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase II,Single-arm Study to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 1st Generation EGFR-TKI Due to Acquisition of EGFR T790M

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.

NCT03543683 Non-Small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV EGFR T790M
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Osimertinib

Description: 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.

Type: Drug

osimertinib and aspirin

Name: Aspirin

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

Type: Drug

osimertinib and aspirin


Primary Outcomes

Description: To evaluate the response to therapy and 1 year median progression-free survival(PFS) rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .

Measure: 1-year median progression-free survival(PFS) rates according to resist 1.1

Time: 3years

Secondary Outcomes

Description: To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .

Measure: median PFS according to resist 1.1

Time: 3years

Description: To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI

Measure: median overall survival(OS) according to resist 1.1

Time: 3years

Purpose: Treatment

Single Group Assignment


There are 2 SNPs

SNPs


1 C797S

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---


2 T790M

A Phase II,Single-arm Study to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 1st Generation EGFR-TKI Due to Acquisition of EGFR T790M. --- T790M ---

Combination of Osimertinib and Aspirin to Treat 1st Generation Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor(EGFR-TKI)Resistance Non-small Cell Lung Cancer ( NSCLC) 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. --- T790M ---

The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations. --- T790M ---

To evaluate the response to therapy and 1 year median progression-free survival(PFS) rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .. median PFS according to resist 1.1. --- T790M ---

To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .. median overall survival(OS) according to resist 1.1. --- T790M ---

To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI. --- T790M ---

Non-Small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV EGFR T790M Lung Neoplasms Carcinoma, Non-Small-Cell Lung Reversible small-molecule EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have shown dramatic therapeutic efficacy in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations, and have been recommended as the standard first-line therapy in these patients. --- T790M ---

Osimertinib is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. --- T790M ---

Here, investigators'group observed that in clinic, several patients who took osimertinib and aspirin together have shown excellent effect.Investigators therefore conduct this clinical trial to observe whether the combination of Aspirin and Osimertinib could enhance efficacy of Osimertinib in lung cancer patients resistant to 1st generation EGFR-TKI with T790M. --- T790M ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1