Non-small Cell Lung Cancer Stage III, Non-Small-Cell Lung Cancer Metastatic
Conditions
Keywords
Non-small Cell Lung Cancer, circulating tumor DNA, T790M, amplification refractory mutation system, digital droplet PCR
Brief summary
The purpose of this study is to compare the frequency and abundance of T790M mutation among the different Clinical modes of EGFR-TKI failure.
Detailed description
An observational, non-interventional, multi-central study of comparison of the frequency and abundance of T790M mutation using both amplification refractory mutation system (ARMS) and digital droplet PCR (ddPCR) methods among the different Clinical modes of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) failure
Interventions
Sponsors
First People's Hospital of Hangzhou
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed stage IIIB/IV NSCLC. * Investigator confirmed progression according RECIST 1.1 during EGFR-TKI treatment within 28 days of the enrollment * Activating mutation (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) in the EGFR gene or have had at least partial response with EGFR TKI lasting ≥ 6 months * Patient must be able to comply with the protocol
Exclusion criteria
* Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined disease progression for more than 28 days while on previous EGFR-TKI treatment. * Patient has been treated with any investigational agent for any indication within 4 weeks of study treatment. * Histologically confirmed small cell lung cancer or other metastatic tumors * Patient with no histologic or cytological diagnosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With T790M Mutation Detected by Amplification Refractory Mutation System (ARMS) Assay | up to 2 years | The investigators will describe the number of T790M mutation on ctDNA detected by ARMS assay in patients with non-small cell lung cancer (NSCLC) resistant to tyrosine kinase inhibitors (TKIs). |
| Abundance of T790M Mutation Detected by Digital Droplet PCR (ddPCR) Assay in Each Individual Patient | up to 2 years | The investigators will describe the abundance of T790M mutation on ctDNA detected by ddPCR assay in patients with NSCLC resistant to TKIs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | up to 2 years | The investigators will describe the number of participants with T790M mutation in each different clinical mode of TKI failure by ARMS and ddPCR, and employ chi-square test to analyze the distribution of T790M mutation by ARMS and ddPCR in patients among the different Clinical modes of TKI failure. |
| Differences of T790M Mutation by ddPCR Among the Different Clinical Modes of TKI Failure | up to 2 years | The investigators will employ Analysis of Variance (ANOVA) method to analyze the differences of T790M mutation by ddPCR in patients among the different Clinical modes of TKI failure. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TKI-PD Patients with advanced or recurrent NSCLC patients had progressed during EGFR-TKIs treatment | 314 |
| Total | 314 |
Baseline characteristics
| Characteristic | TKI-PD |
|---|---|
| Age, Continuous | 63 years |
| Region of Enrollment China | 314 participants |
| Sex: Female, Male Female | 177 Participants |
| Sex: Female, Male Male | 137 Participants |
| Stage IIIA | 54 participants |
| Stage IIIB | 21 participants |
| Stage IV | 239 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 314 |
| serious Total, serious adverse events | 0 / 314 |
Outcome results
Primary
Abundance of T790M Mutation Detected by Digital Droplet PCR (ddPCR) Assay in Each Individual Patient
The investigators will describe the abundance of T790M mutation on ctDNA detected by ddPCR assay in patients with NSCLC resistant to TKIs.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TKI-PD | Abundance of T790M Mutation Detected by Digital Droplet PCR (ddPCR) Assay in Each Individual Patient | 0 percentage of total ctDNA |
Primary
Number of Patients With T790M Mutation Detected by Amplification Refractory Mutation System (ARMS) Assay
The investigators will describe the number of T790M mutation on ctDNA detected by ARMS assay in patients with non-small cell lung cancer (NSCLC) resistant to tyrosine kinase inhibitors (TKIs).
Time frame: up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TKI-PD | Number of Patients With T790M Mutation Detected by Amplification Refractory Mutation System (ARMS) Assay | 97 participants |
Secondary
Differences of T790M Mutation by ddPCR Among the Different Clinical Modes of TKI Failure
The investigators will employ Analysis of Variance (ANOVA) method to analyze the differences of T790M mutation by ddPCR in patients among the different Clinical modes of TKI failure.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TKI-PD | Differences of T790M Mutation by ddPCR Among the Different Clinical Modes of TKI Failure | 0 percentage of total ctDNA |
| Brain Limited | Differences of T790M Mutation by ddPCR Among the Different Clinical Modes of TKI Failure | 0 percentage of total ctDNA |
| Other Sites Failures | Differences of T790M Mutation by ddPCR Among the Different Clinical Modes of TKI Failure | 0.56 percentage of total ctDNA |
p-value: <0.05ANOVA
Secondary
Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure
The investigators will describe the number of participants with T790M mutation in each different clinical mode of TKI failure by ARMS and ddPCR, and employ chi-square test to analyze the distribution of T790M mutation by ARMS and ddPCR in patients among the different Clinical modes of TKI failure.
Time frame: up to 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TKI-PD | Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | T790M positive by ARMS | 49 participants |
| TKI-PD | Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | T790M positive by ddPCR | 78 participants |
| Brain Limited | Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | T790M positive by ARMS | 2 participants |
| Brain Limited | Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | T790M positive by ddPCR | 7 participants |
| Other Sites Failures | Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | T790M positive by ddPCR | 62 participants |
| Other Sites Failures | Number of T790M Mutation by ARMS and ddPCR Assays in Each Different Clinical Modes of TKI Failure | T790M positive by ARMS | 46 participants |
p-value: <0.05Chi-squared