Ignite Creation Date:
2024-05-06 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 12:23 PM
Study NCT ID:
NCT03136523
Status:
COMPLETED
Last Update Posted:
2019-03-14
First Post:
2017-04-21
Brief Title:
Tissue Microarrays TMAs Construction in Lung Cancer Samples
Sponsor:
Kostas NSyrigos
Organization:
Oncology Center of Biochemical Education And Research
Study Overview
Official Title:
Evaluation of the Prognostic and Predictive Significance of EGFR Kirsten Rat Sarcoma KRAS Anaplastic Lymphoma Kinase Programmed Death-Ligand 1 PD-L1 Protein and Microsatellite Instability MSI in Lung Cancer
Status:
COMPLETED
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LUNGTMA
Brief Summary:
Construction of a large cohort of lung cancer patients to evaluate the Prognostic and Predictive Significance of the molecular biomarkers Epidermal growth factor receptor EGFR KRAS Anaplastic lymphoma kinase EML4-ALK Programmed Death-Ligand 1 PD-L1 protein and Microsatellite Instability MSI in lung cancer A tissue microarray-based study of 500 cases
Detailed Description:
Research hypothesis The research hypothesis for this study is that the expressionstatus of various molecular biomarkers mainly including EGFR KRAS ALK PD-L1 and MSI may confer additional prognostic in terms of disease outcome ie PFS and OS andor predictive in terms of treatment response information for lung cancer patients
The research hypothesis is reflected in the primary objective of this study which is to further evaluate the prognostic and predictive significance of currently existing molecular markers EGFR KRAS ALK PD-L1 and MSI as well as of future biomarkers that may evolve Secondary objectives include the evaluation of the differential expressionstatus of the examined biomarkers EGFR KRAS ALK PD-L1 and MSI and standard clinicopathologic parameters including PFS OS and treatment response as well as age gender smoking historystatus performance status PS serum lactate dehydrogenase LDH and albumin levels disease stage tumor size histology and grade presence or absence of brain metastases presence or absence of liver metastases and number of metastatic sites all at diagnosis and treatment data type of treatments received and treatment response Potential correlationsinteractions between the examined biomarkers will also be explored
Rationale for conducting this study Rationale for biomarker selection The primary aim of this study is to further clarify the differential expressionstatus and frequency of EGFR and KRAS mutations ALK rearrangements PD-L1 protein and MSI as well as their association with various clinicopathologic parameters including treatment response progression-free survival PFS and overall survival OS in a large and heterogeneous cohort of patients with lung cancer including both NSCLC and SCLC
EGFR KRAS and ALK are among the most clinically important biomarkers of treatment response in NSCLC EGFR and ALK represent major therapeutic targets in NSCLC However relatively little is known as regards their expression and potential clinical significance in SCLC
PD-L1 protein represents a candidate biomarker of prognosis as well as therapeutic target Previous experimental and clinical research data have strongly suggested that immune check point inhibitors including anti-PD-1 and anti-PD-L1 agents may increase tumor cell vulnerability to immune destruction and potentially improve survival of patients with lung cancer The MSI phenotype may also affect prognosis of NSCLC patients and response to treatment including immune checkpoint blockade with PD-1 inhibitors
Rationale for the use of TMAs TMA-based immunohistochemistry represents an innovative diagnostic approach with several important advantages as compared to conventional immunohistochemical methods As widely acknowledged the main and foremost advantage of this technology is its impressive potential to maximize and preserve tissue resources Moreover it provides an efficient and cost-effective alternative to conventional histopathologic processing for the performance of large-scale analyses with considerable savings in time labor reagents and other laboratory consumables 31 Most importantly and aside from cost reductions alone another advantage of the TMA technique is the identical treatment of all studied samples Since TMAs contain multiple tissue samples on a single slide all these specimens are simultaneously subjected to the exact same environmental and experimental conditions ie temperature reagents concentration incubation time antigen retrieval procedure This stands in sharp contrast to the substantial slide-to-slide variability associated with individual processing of whole tissue sections thus underlying the superior standardization of the TMA technology 30
Briefly construction of TMAs will allow for simultaneous analysis of a large number of biomarkers either at the protein or at the RNA level
Benefitrisk and ethical assessment Potential risks and benefits As this is a non-interventional study there are no physical potential risks to participants other than potential breach of confidentiality for the same reason there are no potential benefits to participants
The research hypothesis is reflected in the primary objective of this study which is to further evaluate the prognostic and predictive significance of currently existing molecular markers EGFR KRAS ALK PD-L1 and MSI as well as of future biomarkers that may evolve Secondary objectives include the evaluation of the differential expressionstatus of the examined biomarkers EGFR KRAS ALK PD-L1 and MSI and standard clinicopathologic parameters including PFS OS and treatment response as well as age gender smoking historystatus performance status PS serum lactate dehydrogenase LDH and albumin levels disease stage tumor size histology and grade presence or absence of brain metastases presence or absence of liver metastases and number of metastatic sites all at diagnosis and treatment data type of treatments received and treatment response Potential correlationsinteractions between the examined biomarkers will also be explored
Rationale for conducting this study Rationale for biomarker selection The primary aim of this study is to further clarify the differential expressionstatus and frequency of EGFR and KRAS mutations ALK rearrangements PD-L1 protein and MSI as well as their association with various clinicopathologic parameters including treatment response progression-free survival PFS and overall survival OS in a large and heterogeneous cohort of patients with lung cancer including both NSCLC and SCLC
EGFR KRAS and ALK are among the most clinically important biomarkers of treatment response in NSCLC EGFR and ALK represent major therapeutic targets in NSCLC However relatively little is known as regards their expression and potential clinical significance in SCLC
PD-L1 protein represents a candidate biomarker of prognosis as well as therapeutic target Previous experimental and clinical research data have strongly suggested that immune check point inhibitors including anti-PD-1 and anti-PD-L1 agents may increase tumor cell vulnerability to immune destruction and potentially improve survival of patients with lung cancer The MSI phenotype may also affect prognosis of NSCLC patients and response to treatment including immune checkpoint blockade with PD-1 inhibitors
Rationale for the use of TMAs TMA-based immunohistochemistry represents an innovative diagnostic approach with several important advantages as compared to conventional immunohistochemical methods As widely acknowledged the main and foremost advantage of this technology is its impressive potential to maximize and preserve tissue resources Moreover it provides an efficient and cost-effective alternative to conventional histopathologic processing for the performance of large-scale analyses with considerable savings in time labor reagents and other laboratory consumables 31 Most importantly and aside from cost reductions alone another advantage of the TMA technique is the identical treatment of all studied samples Since TMAs contain multiple tissue samples on a single slide all these specimens are simultaneously subjected to the exact same environmental and experimental conditions ie temperature reagents concentration incubation time antigen retrieval procedure This stands in sharp contrast to the substantial slide-to-slide variability associated with individual processing of whole tissue sections thus underlying the superior standardization of the TMA technology 30
Briefly construction of TMAs will allow for simultaneous analysis of a large number of biomarkers either at the protein or at the RNA level
Benefitrisk and ethical assessment Potential risks and benefits As this is a non-interventional study there are no physical potential risks to participants other than potential breach of confidentiality for the same reason there are no potential benefits to participants
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ESR-15-11047 | OTHER_GRANT | Astrazeneca SA | None |