Trial Title:
GUIDE.MRD-01-CRC: Clinical Validation and Benchmarking of Top Performing CtDNA Diagnostics - Colorectal Cancer
NCT ID:
NCT06111105
Condition:
Colorectal Cancer Stage III
Liver Metastasis Colon Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Circulating tumor DNA
ctDNA diagnostics
Minimal residual disease
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Summary:
Improving personalized cancer treatments and finding the best strategies to treat each
patient relies on using new diagnostic technologies. Currently, for colorectal cancer,
the methods used to decide who gets additional post-surgery 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 after surgery. 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-01-CRC is a part of the GUIDE.MRD project.
Detailed description:
GUIDE.MRD-01-CRC 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 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-01-CRC is to prospectively
collect the clinical samples needed to enable assessment of the performance of ctDNA
diagnostics in the setting of colorectal cancer (CRC). There are two main scenarios where
ctDNA diagnostic is useful in CRC:
Stage III CRC (locally advanced, non-metastasized disease): This patient group is
particularly relevant because adjuvant therapy is recommended for all stage III patients,
due to their high recurrence risk, ~25%. Nevertheless, most patients do not recur, and
most of these do not need therapy at all, because they were already cured by surgery
alone, which leads to substantial overtreatment. Furthermore, the 25% 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 of stage III CRC. This
clinical dilemma will be addressed with the first cohort of GUIDE.MRD-01-CRC.
Metastatic CRC with isolated liver metastases. Metastatic CRC with liver metastases is a
unique tumor type in that surgical resection or complete ablation of the metastases, is
the standard of care. In virtually all other tumor types, resection of liver metastases
is considered only within clinical trials or in exceptional clinical circumstances. In
contrast, resection, or ablation of colorectal cancer liver metastases (CRLM) are
routinely performed with curative intention, and the overall 5-year survival is around
50%. Most relapses present within three years after operative intervention. The clinical
benefit of adjuvant chemotherapy is currently a matter of debate, due to limited data
from randomized controlled trials and recent results that indicate inferior overall
survival (OS) in patients who received adjuvant therapy (JCOG0603). Based on these and
earlier data (EORTC Trial 40983) that failed to show an OS benefit of adjuvant therapy
after CRLM resection, it can be assumed that most patients are treated unnecessarily with
chemotherapy, and those patients that could receive targeted agents are missed. No
histological or clinical markers are available to guide decisions on adjuvant treatment.
In this setting, ctDNA could be valuable to guide decisions on adjuvant chemotherapy
(yes/no), the addition of biologicals such as anti-VEGF and anti-EGFR agents, targeted
therapies in the case of BRAF mutations, or the presence of microsatellite instability
(MSI), for example.
Primary objectives:
- To assess the performance of ctDNA diagnostics using samples collected at the
two-landmark time-points "post-surgery" and "post-adjuvant therapy". 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 adjuvant
therapy
Criteria for eligibility:
Study pop:
Colorectal cancer stage III: patient with stage III colorectal cancer treated with
curative-intent surgery and adjuvant chemotherapy
Colorectal cancer liver metastasis: patient with colorectal cancer liver metastasis
Sampling method:
Non-Probability Sample
Criteria:
Colorectal cancer stage III
Inclusion Criteria:
- Colorectal cancer, UICC stage III
- Has received curative-intent resection and is a candidate for adjuvant chemotherapy
- Patient able to understand and sign written informed consent
Exclusion Criteria:
- Hereditary colorectal cancer linked to familial colonic polyposis or Lynch syndrome
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
- Verified distant metastases
- Not treated with adjuvant chemotherapy despite indication (incomplete treatment not
included)
- Treated with neoadjuvant chemo-radiation therapy
- No tissue sample available for the project, or tumor content in the tissue sample is
<20%
- Synchronous colorectal and non-colorectal cancer diagnosed per operative (except
skin cancer other than melanoma)
- Other cancers (excluding colorectal cancer or skin cancer other than melanoma)
within 3 years from eligibility screening
- 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
Colorectal cancer liver metastasis
Inclusion Criteria:
- Colorectal cancer liver metastasis
- Planned for curative-intent treatment
- Performance status 0-1
Exclusion Criteria:
- Liver cirrhosis
- Extrahepatic metastases
- Other cancer within the last 5 years
- Intervention not performed with curative intent
- No tissue available from CRLM or primary tumor
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Abteilung für Onkologie, Medizinische Universität Graz
Address:
City:
Graz
Zip:
8010
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Armin Gerger, MD, PhD
Phone:
+43-316-385-80625
Email:
armin.gerger@medunigraz.at
Facility:
Name:
Ordenskrankenhaus Graz Mitte
Address:
City:
Graz
Zip:
8010
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Felix Aigner, MD, PhD
Phone:
+43-316-7067-13002
Email:
Felix.Aigner@bbgraz.at
Facility:
Name:
Bispebjerg Hospital
Address:
City:
Copenhagen
Zip:
2400
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Nis Hallundbæk Schlesinger
Email:
Nis.Hallundbaek.Schlesinger@regionh.dk
Facility:
Name:
Herlev Hospital
Address:
City:
Herlev
Zip:
2730
Country:
Denmark
Status:
Not yet recruiting
Contact:
Last name:
Mads F Klein, MD, Ph.D
Email:
mads.falk.klein@regionh.dk
Contact backup:
Last name:
Jeppe Kildsig, MD
Email:
Jeppe.Kildsig@regionh.dk
Facility:
Name:
Aarhus University Hospital
Address:
City:
Aarhus
Zip:
8000
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Lene H Iversen, MD, DMSc
Email:
lene.h.iversen@dadlnet.dk
Facility:
Name:
Gødstrup Hospital
Address:
City:
Herning
Zip:
7400
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Claudia Jaensch, MD, PhD
Email:
Claudia.Jaensch@goedstrup.rm.dk
Facility:
Name:
Regional Hospital Horsens
Address:
City:
Horsens
Zip:
8700
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Kåre A Gotschalck, MD, Ph.D
Email:
kaarsune@rm.dk
Facility:
Name:
Regional Hospital Randers
Address:
City:
Randers
Zip:
8930
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Peter Bondeven, MD, PhD
Email:
petefred@rm.dk
Facility:
Name:
Regional Hospital Viborg
Address:
City:
Viborg
Zip:
8800
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Uffe S Løve, MD, PhD
Email:
uffescho@rm.dk
Facility:
Name:
Aalborg University Hospital
Address:
City:
Aalborg
Zip:
9000
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Ole Thorlacius-Ussing, MD, PhD
Email:
otu@rn.dk
Facility:
Name:
Odense University Hospital
Address:
City:
Odense
Zip:
5000
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Per Vadgaard Andersen, MD, PhD
Email:
Per.vadgaard.andersen@rsyd.dk
Facility:
Name:
LCCRH (Laboratoire Cellules Circulantes Rares Humaines) - CHU de Montpellier
Address:
City:
Montpellier
Zip:
34295
Country:
France
Status:
Recruiting
Contact:
Last name:
Catherine Alix-Panabiéres, PhD
Phone:
+33 (0)4 11 75 99 31
Email:
c-panabieres@chu-montpellier.fr
Contact backup:
Last name:
Thomas Bardol, MD
Phone:
+33 (0)4 11 75 99 31
Email:
t-bardol@chu-montpellier.fr
Facility:
Name:
Department of General-, Visceral- and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Thilo Hackert, MD, MBA
Phone:
+49 (0) 40 7410 - 52401
Email:
allgemeinchirurgie@uke.de
Contact backup:
Last name:
Nathaniel Melling, MD
Phone:
+49 (0) 40 7410 - 50162
Email:
n.melling@uke.de
Facility:
Name:
Universitätsklinikum Hamburg-Eppendorf
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Daniel J Smit, MD, PhD
Phone:
+49 (0) 40 7410 - 57495
Email:
d.smit@uke.de
Facility:
Name:
Karolinska University Hospital
Address:
City:
Huddinge
Zip:
14183
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Marco Gerling, MD
Phone:
0468-123 800 00
Email:
marco.gerling@ki.se
Start date:
August 1, 2023
Completion date:
July 31, 2030
Lead sponsor:
Agency:
Claus Lindbjerg Andersen
Agency class:
Other
Collaborator:
Agency:
Medical University of Graz
Agency class:
Other
Collaborator:
Agency:
University Medical Centre of Montpellier
Agency class:
Other
Collaborator:
Agency:
Universitätsklinikum Hamburg-Eppendorf
Agency class:
Other
Collaborator:
Agency:
University of Aarhus
Agency class:
Other
Collaborator:
Agency:
Karolinska Institutet, Stockholm, Sweden
Agency class:
Other
Source:
University of Aarhus
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06111105
https://www.guidemrd-horizon.eu/
