The study aims to investigate the efficacy and safety of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
Name: AZD9291 80mg oral each day
Name: Radiation therapy
Description: To assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI by PFSo
Measure: PFSo (overall progression free survival) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: PFSe (extracranial progression-free survival) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: PFSi (intracranial progression-free survival) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: ORRo (overall objective response rate) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: ORRe (extracranial objective response rate) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: ORRi (intracranial objective response rate) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: DCRo (overall disease control rate) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: DCRe (extracranial disease control rate) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: DCRi (intracranial disease control rate) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: DoRo (overall duration of response) Time: 3 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: DoRe (extracranial duration of response) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: DoRi (intracranial duration of response) Time: 2 yearsDescription: To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc.
Measure: OS(overall survival) Time: 3 yearsDescription: To evaluate the safety and tolerability profile of AZD9291 and subgroups such as AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy and etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
Measure: Adverse events/Serious adverse events Time: 2 yearsDescription: To assess disease-related symptoms and QoL in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
Measure: QoL Time: 2 yearsDescription: To assess disease-related symptoms and cognitive function in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.
Measure: Cognitive function Time: 2 yearsDescription: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
Measure: T790M mutation positive rate Time: 2 yearsDescription: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
Measure: Concordance of T790M status between CSF and plasma Time: 2 yearsDescription: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
Measure: Change of imputed ctDNA concentration before and after treatment Time: 2 yearsDescription: To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.
Measure: Proportion of each genetic mutation Time: 2 yearsDescription: To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology.
Measure: Change from baseline in glucose and protein levels Time: 2 yearsDescription: To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology.
Measure: Change from baseline in tumor cell count Time: 2 yearsDescription: To explore potential relation between relevant efficacy measures, biomarkers or safety variables and plasma or CSF concentration of AZD9291 (or metabolites).
Measure: AZD9291 concentration level in CSF/plasma Time: 2 yearsAllocation: N/A
Single Group Assignment
There is one SNP
Open Label, Multi-center, Prospective Study to Investigate the Efficacy and Safety of AZD9291 in Brain Metastases From Patients With EGFR T790M Positive NSCLC Who Have Received Prior Therapy With an EGFR-TKI. --- T790M ---
Open Label, Prospective Study to Investigate Efficacy and Safety of AZD9291 in BM From NSCLC Patients With EGFR T790M The study aims to investigate the efficacy and safety of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI. --- T790M ---
Open Label, Prospective Study to Investigate Efficacy and Safety of AZD9291 in BM From NSCLC Patients With EGFR T790M The study aims to investigate the efficacy and safety of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI. --- T790M --- --- T790M ---
To assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI by PFSo. --- T790M ---
To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. --- T790M ---
To evaluate the safety and tolerability profile of AZD9291 and subgroups such as AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy and etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.. QoL. --- T790M ---
AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.. Cognitive function. --- T790M ---
AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.. T790M mutation positive rate. --- T790M ---
AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.. T790M mutation positive rate. --- T790M --- --- T790M ---
To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.. Concordance of T790M status between CSF and plasma. --- T790M ---
To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.. Concordance of T790M status between CSF and plasma. --- T790M --- --- T790M ---
To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.. Change of imputed ctDNA concentration before and after treatment. --- T790M ---
To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.. Proportion of each genetic mutation. --- T790M ---
To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples.. Change from baseline in glucose and protein levels. --- T790M ---
To explore potential relation between relevant efficacy measures, biomarkers or safety variables and plasma or CSF concentration of AZD9291 (or metabolites).. Inclusion Criteria: 1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures 2. Metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation. --- T790M ---
Inclusion Criteria: 1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures 2. Metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation. --- T790M ---
EGFR-TKI Resistant Mutation Nonsmall Cell Lung Cancer AZD9291 Brain Metastases Neoplasm Metastasis Carcinoma, Non-Small-Cell Lung Patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI and concurrent with brain metastasis will be enrolled into the study. --- T790M ---