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
NCT ID: NCT02372448
Last Updated: 2020-12-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
NA
206 participants
INTERVENTIONAL
2015-01-23
2019-11-21
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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 advanced/metastatic 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 IIIb/IV 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 patient's 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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
DIAGNOSTIC
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
ALK-positive
ALK positive analysis on CTCs detected by ISET
ALK analysis on CTCs detected by ISET
ALK-negative
ALK negative analysis on CTCs detected by ISET
ALK analysis on CTCs detected by ISET
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
ALK analysis on CTCs detected by ISET
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Histologically confirmed stage IIIb/IV non-squamous NSCLC undergoing biopsy or surgery
* Presence of ALK rearrangement result by FISH analysis (gold standard method) on tumor tissue
* Signed specific informed consent approved by the Institutional Review Board prior to patient entry
* Affiliation to the social security system
Exclusion Criteria
* Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Centre Hospitalier Universitaire de Nice
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Paul HOFMAN, Pr
Role: PRINCIPAL_INVESTIGATOR
Centre Hospitalier Universitaire de Nice
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centre François Baclesse
Caen, , France
Grenoble university hospital
Grenoble, , France
Marseille University Hospital
Marseille, , France
Nancy university hospital
Nancy, , France
Centre Antoine Lacassagne
Nice, , France
CHU de Nice
Nice, , France
Hôpital Tenon
Paris, , France
Institut arnault tzanck
Saint-Laurent-du-Var, , France
Toulouse University Hospital
Toulouse, , France
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, , France
Institut Gustave Roussy
Villejuif, , France
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
13-APN-01
Identifier Type: -
Identifier Source: org_study_id