Trial Title:
Clinical Validation and Benchmarking of Top Performing ctDNA Diagnostics - Stage III NSCLC
NCT ID:
NCT06111807
Condition:
Lung Cancer Stage III
Conditions: Official terms:
Lung Neoplasms
Conditions: Keywords:
Circulating tumor DNA
ctDNA diagnostics
Minimal residual disease
Sensitivity
Specificity
complete pathological response
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
ctDNA
Description:
ctDNA will be tested retrospectively, no treatment decisions will be made prospectively
Arm group label:
Chemo-radiotherapy
Arm group label:
Neoadjuvant and surgery
Arm group label:
Surgery and adjuvant immunotherapy
Summary:
Improving personalized cancer treatments and finding the best strategies to treat each
patient relies on using new diagnostic technologies. Currently, for non small cell lung
cancer (NSCLC), the methods used to decide who gets additional post radical (surgery or
definite chemo-radiotherapy) treatment are suboptimal. Some patients get too much
treatment, while others do not get enough.
There is a new way to explore if there is any cancer left in a patient's body using
circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs
more treatment. Even though many tests have been developed, it has yet to be determined
which test performs best at relevant time points.
The GUIDE.MRD consortium is a group of experts, including scientists, technology, and
pharmaceutical companies. The consortium is working on creating a reliable standard for
the ctDNA tests, validating their clinical utility, and collecting data to help decide on
the best treatment for each patient.
GUIDE.MRD-03-NSCLC is a part of the GUIDE.MRD project.
Detailed description:
GUIDE.MRD-03-NSCLC is a part of WP3 of the overarching GUIDE.MRD project. Each study
chair has a local clinical trial protocol where patients are recruited. After the end of
recruitment, samples will be analyzed under the GUIDE.MRD consortium.
The overall aim of GUIDE.MRD is to investigate the clinical utility of ctDNA analysis to
predict and guide the choice of multi-modal therapies prospectively. The fundamental
steps towards this aim are assessment and benchmarking of the many available ctDNA
diagnostics to identify the best-suited tests for clinical application. Clinical samples
will be used to benchmark ctDNA diagnostics and assess their true clinical performance.
The samples should reflect clinical situations where the ctDNA diagnostics are
particularly useful, such as post-operatively, post-adjuvant, during chemotherapy, and
longitudinally during post-treatment surveillance. In these situations, ctDNA diagnostics
could be used to either monitor treatment response (in case of MRD after surgery or
definite chemoradiotherapy) or to identify relapse at an early time point. Based on ctDNA
information, medical treatment could be changed, or radiology could be used to reveal the
location of residual disease.
The rationale for the observational clinical study GUIDE.MRD-03-NSCLC is to prospectively
collect the clinical samples needed to enable assessment of the performance of ctDNA
diagnostics in the setting of non small cell lung cancer (NSCLC). There are three main
scenarios where ctDNA diagnostic is useful in NSCLC in a MRD setting:
For this study stage III NSCLC will be included treated with curative intent using:
1. chemo-radiotherapy (concurrent or sequential) followed by adjuvant immunotherapy.
This patient group is particularly relevant because adjuvant therapy is recommended
for all stage III patients (in some countries for those with PD-L1>1% only), due to
their high recurrence risk around 58%. Additionally, most of these do not need
therapy at all, because they were already cured by chemo-radiotherapy alone, which
leads to substantial overtreatment. Furthermore, the 58% of patients who recur
despite both chemoradiotherapy and adjuvant immunotherapy, probably could benefit
from further multimodal therapies. The challenge is, however, that currently there
is no marker in clinical use that can identify those patients with residual disease
and need for therapy. Circulating tumor DNA is potentially such a marker.
2. Neoadjuvant treatment followed by surgery (or radiotherapy with curative intent). In
this setting up to 30% have a complete pathological response (pCR). These patients
are probably cured by the neoadjuvant treatment alone, where surgery thus might have
been avoided if the MRD biomarker would be sensitive enough. Patients that did not
receive a pCR do worse with a median overall survival around 24 month even when they
are treated with immunecheckpoint inhibitors adjuvantly. Better strategies for
selecting patients and treatments are urgently needed here as well. Again ctDNA
could be a marker that may help here when sensitive enough to select those that are
negative for no adjuvant and those that are positive for ctDNA guided multimodality
treatment.
3. Surgery followed by adjuvant chemotherapy and immunotherapy. Patients in this
setting may be treated by immunotherapy adjuvantly only when PD-L1>1% (FDA) or
PD-L1>50% (EMA). Also here recurrence risk is high around 50%. Additionally, most of
these do not need therapy at all, because they were already cured by surgery alone,
which leads to substantial overtreatment. Furthermore, the 50% of patients who recur
despite both surgery and adjuvant therapy, probably could benefit from further
multimodal therapies. The challenge is, however, that currently there is no marker
in clinical use that can identify those patients with residual disease and need for
therapy. Circulating tumor DNA is potentially such a marker.
However, currently, it is unknown, which, if any,of the many different ctDNA diagnostics
developed in recent years have the required, performance to provide clinical utility in
the management in these settings of stage III NSCLC.
Primary objectives:
To assess the performance of ctDNA diagnostics using samples collected at four to five
-landmark time-points "baseline"; "post neoadjuvant treatment"; "post-surgery or
chemoradiotherapy"; "post-adjuvant therapy" and "at the end of study or disease
progression".Sensitivity, specificity, and positive and negative predictive values of the
ctDNA diagnostics will be determined to enable a head-to-head performance assessment and
benchmarking of ctDNA diagnostics.
Secondary objectives To assess the ctDNA stratified 3-year recurrence-free survival
(RFS). To assess the lead time between ctDNA detection and clinical recurrence. To assess
the capacity of the ctDNA diagnostics to predict response to neoadjuvant therapy.
To assess the capacity of the ctDNA diagnostics to predict response to adjuvant therapy.
Criteria for eligibility:
Study pop:
Stage III NSCLC with curative intent treatment
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- NSCLC, clinical tumor stage III (cT1-4, cN0-3, M0).
- Patient 18 years or older.
- Scheduled for curative intent treatment (surgery and/or radiotherapy).
- Patient able to understand and sign written informed consent.
- Baseline contrast enhanced CT thorax abdomen (or PET/CT), MRI (or CT) brain,
Pulmonary function tests (at least FEV1 and DLCO/KCO).
- Ability to obtain sufficient tumor material (≥50ng tumor DNA, FFPE ). Either at
baseline or after surgery.
Exclusion Criteria:
- Verified distant metastases.
- With synchronous NSCLC cancer and non-NSCLC cancer (except skin cancer other than
melanoma).
- With other cancers (excluding NSCLC or skin cancer other than melanoma, or cancers
treated curatively with follow up of more than 5 years without recurrence).
- Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude),
inability to return for subsequent visits) and/or otherwise considered by the
Investigator to be unlikely to complete the study.
- No tissue sample available for the project, or tumor content in the tissue sample is
<20%
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Locations:
Facility:
Name:
Centre Hospitalier Universitaire de Nice
Address:
City:
Nice
Zip:
06000
Country:
France
Status:
Recruiting
Contact:
Last name:
Jonathan Benzaquen, MD,PhD
Phone:
4 92 03 82 81
Phone ext:
+33
Email:
benzaquen.j@chu-nice.fr
Contact backup:
Last name:
Jennifer Griffonnet
Phone:
4 92 03 82 81
Phone ext:
+33
Email:
griffonnet.j@chu-nice.fr
Investigator:
Last name:
Paul Hofman, MD,PhD
Email:
Principal Investigator
Investigator:
Last name:
Jonathan Benzaquen, MD
Email:
Sub-Investigator
Investigator:
Last name:
Victoria Ferrari, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jean Philippe Berthet, MD
Email:
Sub-Investigator
Facility:
Name:
Antoine Lacassagne Center
Address:
City:
Nice
Zip:
06189
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Ferrari Victoria, MD
Phone:
4 92 03 15 38
Phone ext:
+33
Email:
Victoria.FERRARI@nice.unicancer.fr
Contact backup:
Last name:
Nicola Martin, MD
Phone:
4 92 03 15 38
Phone ext:
+33
Email:
nicolas.martin@nice.unicancer.fr
Facility:
Name:
Department of thoracic oncology- LungenClinic Großhansdorf
Address:
City:
Großhansdorf
Zip:
22927
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Mustafa Abdo, MD
Phone:
04102601-2412
Phone ext:
0049
Email:
m.abdo@lungenclinic.de
Investigator:
Last name:
Martin Reck, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Mustafa Abdo, MD
Email:
Principal Investigator
Facility:
Name:
Ommelander Ziekenhuis Groningen
Address:
City:
Scheemda
Zip:
9679BJ
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Remge Pieterman, MD
Phone:
088066100
Phone ext:
+31
Email:
r.pieterman@ozg.nl
Contact backup:
Last name:
Alice Staats-Niemeijer, BSC
Phone:
088066100
Phone ext:
+31
Email:
a.niemeijer@ozg.nl
Facility:
Name:
University Medical Center Groningen, Departments of Pulmonology and Pathology
Address:
City:
Groningen
Zip:
9713GZ
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
T.Jeroen Hiltermann, MD
Phone:
503612357
Phone ext:
0031
Email:
t.j.n.hiltermann@umcg.nl
Contact backup:
Last name:
Ed Schuuring, Dr
Phone:
503619623
Phone ext:
0031
Email:
e.schuuring@umcg.nl
Investigator:
Last name:
T.Jeroen Hiltermann, MD, PhD
Email:
Principal Investigator
Start date:
November 10, 2023
Completion date:
July 31, 2030
Lead sponsor:
Agency:
University Medical Center Groningen
Agency class:
Other
Collaborator:
Agency:
LungenClinic Grosshansdorf
Agency class:
Other
Collaborator:
Agency:
Centre Hospitalier Universitaire de Nice
Agency class:
Other
Source:
University Medical Center Groningen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06111807
http://www.guidemrd-horizon.eu/
