Ignite Creation Date:
2024-05-06 @ 3:47 AM
Last Modification Date:
2024-10-26 @ 11:38 AM
Study NCT ID:
NCT02372448
Status:
COMPLETED
Last Update Posted:
2020-12-08
First Post:
2014-09-22
Brief Title:
Multicenter Validation of the Sensitivity of Theranostic ALK Rearrangement Detection by FISH Analysis and Prevalence of Escaping Mutations in Circulating Tumor Cells for the Non-invasive Management of Lung Cancer Patients
Sponsor:
Centre Hospitalier Universitaire de Nice
Organization:
Centre Hospitalier Universitaire de Nice
Study Overview
Official Title:
Multicenter Validation of the Sensitivity of Theranostic ALK Rearrangement Detection by FISH Analysis and Prevalence of Escaping Mutations in Circulating Tumor Cells for the Non-invasive Management of Lung Cancer Patients
Status:
COMPLETED
Status Verified Date:
2020-12
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:
STALKLUNG01
Brief Summary:
Patients eligibility to targeted therapies relies on a molecular test performed on a tumor sample collected by biopsy This invasive procedure is associated with a relative high risk of morbidity and requires the intervention of a costly and important technical platform Thus inoperable patients can be deprived from potentially more efficient therapies A liquid biopsy of Circulating Tumor Cells CTCs present in the blood and their molecular characterization is an appealing alternative to meet an urgent need for these patients Moreover no CTC-based molecular test is currently routinely available
The 5-year survival rate of patients with non-small cell lung carcinoma NSCLC is low Recent reports demonstrated that the detection of an ALK rearrangement in the tumor tissue allows patients with late-stages NSCLC to benefit from crizotinib treatment
However 1 the detection of an ALK rearrangement is currently performed on small biopsies or fine-needle aspirates and can be hindered by the limited tissue quantities available Tumor tissue is difficult to obtain in patients with advancedmetastatic lung cancer for whom surgery is rarely a component of treatment Finding alternative and more effective means of diagnosing an ALK rearrangement are critical issues for identifying patients who may benefit from treatment with crizotinib 2 some patients develop resistance to crizotinib due to de novo ALK mutations
In this setting circulating tumor cells CTCs which have been shown to be detectable by ISET Isolation by Size of Epithelial Tumor Cells method in 80 to 100 of late stages lung cancer patients represent a non-invasive and easily accessible source of tumor material for assessing ALK rearrangement and escaping mutations in a kinetic manner The ISET method was first published in 2000 and several independent teams have now established its high sensitivity and specificity of ISET for NSCLC With ISET specificity can be achieved using the same methods and criteria used by cytopathologists to diagnose solid tumors
The high sensitivity and specificity of ISET are two essential starting points for the feasibility of this present project Low-throughput molecular characterization of CTCs isolated by ISET has also been achieved The remaining challenge consists in developing high-throughput ISET-based molecular tests for personalized medicine that are transferable to the clinics
The Team 1 at the CHU de Nice and the Team 2 at the Gustave Roussy Institute have demonstrated that the detection of an ALK rearrangement in CTC isolated by ISET is feasible and consistent with results obtained in corresponding tumor tissues In this context the aim of this project is to obtain 1 a definitive prospective clinical validation of the use of CTC as an alternative to tumor tissue for ALK analysis-based patients stratification 2 a proof that escaping mutations can be detected early by kinetic analysis of CTC in patients treated by crizotinib ALK rearrangement will be prospectively investigated in CTCs isolated by ISET at diagnosis and during follow up from patients with stage IIIbIV lung cancer and de novo mutations will be searched in patients with resistance to crizotinib This study will provide both clinical and economic benefit to targeted treatment of patients with advanced lung cancer
This project is strongly original as no CTC-based ALK rearrangement test has been independently validated up to now with clinical samples The development of non-invasive theranostic test through the genetic analysis of CTCs is a clinically relevant goal for non-invasive stratification of cancer patients avoiding morbidity related to lung biopsy and surgery It would allow determining patients eligibility to targeted therapies on a blood sample analysis CTC-based ALK test could be useful to guide the choice of ALK targeted therapy in patients with lung cancer Furthermore developing biomarkers based on CTCs analysis would open the way to the non-invasive follow up of aggressive cancers early detection of mutations associated with resistance to targeted therapies and tailoring treatment to a real time analysis of the evolving tumor cell populations This test is expected to markedly improve patients quality of life avoiding invasive diagnostic procedures
The 5-year survival rate of patients with non-small cell lung carcinoma NSCLC is low Recent reports demonstrated that the detection of an ALK rearrangement in the tumor tissue allows patients with late-stages NSCLC to benefit from crizotinib treatment
However 1 the detection of an ALK rearrangement is currently performed on small biopsies or fine-needle aspirates and can be hindered by the limited tissue quantities available Tumor tissue is difficult to obtain in patients with advancedmetastatic lung cancer for whom surgery is rarely a component of treatment Finding alternative and more effective means of diagnosing an ALK rearrangement are critical issues for identifying patients who may benefit from treatment with crizotinib 2 some patients develop resistance to crizotinib due to de novo ALK mutations
In this setting circulating tumor cells CTCs which have been shown to be detectable by ISET Isolation by Size of Epithelial Tumor Cells method in 80 to 100 of late stages lung cancer patients represent a non-invasive and easily accessible source of tumor material for assessing ALK rearrangement and escaping mutations in a kinetic manner The ISET method was first published in 2000 and several independent teams have now established its high sensitivity and specificity of ISET for NSCLC With ISET specificity can be achieved using the same methods and criteria used by cytopathologists to diagnose solid tumors
The high sensitivity and specificity of ISET are two essential starting points for the feasibility of this present project Low-throughput molecular characterization of CTCs isolated by ISET has also been achieved The remaining challenge consists in developing high-throughput ISET-based molecular tests for personalized medicine that are transferable to the clinics
The Team 1 at the CHU de Nice and the Team 2 at the Gustave Roussy Institute have demonstrated that the detection of an ALK rearrangement in CTC isolated by ISET is feasible and consistent with results obtained in corresponding tumor tissues In this context the aim of this project is to obtain 1 a definitive prospective clinical validation of the use of CTC as an alternative to tumor tissue for ALK analysis-based patients stratification 2 a proof that escaping mutations can be detected early by kinetic analysis of CTC in patients treated by crizotinib ALK rearrangement will be prospectively investigated in CTCs isolated by ISET at diagnosis and during follow up from patients with stage IIIbIV lung cancer and de novo mutations will be searched in patients with resistance to crizotinib This study will provide both clinical and economic benefit to targeted treatment of patients with advanced lung cancer
This project is strongly original as no CTC-based ALK rearrangement test has been independently validated up to now with clinical samples The development of non-invasive theranostic test through the genetic analysis of CTCs is a clinically relevant goal for non-invasive stratification of cancer patients avoiding morbidity related to lung biopsy and surgery It would allow determining patients eligibility to targeted therapies on a blood sample analysis CTC-based ALK test could be useful to guide the choice of ALK targeted therapy in patients with lung cancer Furthermore developing biomarkers based on CTCs analysis would open the way to the non-invasive follow up of aggressive cancers early detection of mutations associated with resistance to targeted therapies and tailoring treatment to a real time analysis of the evolving tumor cell populations This test is expected to markedly improve patients quality of life avoiding invasive diagnostic procedures
Detailed Description:
None
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