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JOURNAL ONKOLOGIE – STUDIE

GUIDE.MRD-01-CRC: Clinical Validation and Benchmarking of Top Performing ctDNA Diagnostics - Colorectal Cancer

Rekrutierend

NCT-Nummer:
NCT06111105

Studienbeginn:
August 2023

Letztes Update:
08.08.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Colorectal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Claus Lindbjerg Andersen

Collaborator:
Medical University of Graz, University Medical Centre of Montpellier, Karolinska Institutet, Universitätsklinikum Hamburg-Eppendorf, University of Aarhus,

Studienleiter

Ellen Heitzer, PhD
Study Chair
Medical University of Graz
Klaus Pantel, MD
Study Chair
Universitätsklinikum Hamburg-Eppendorf
Catherine Alix-Panabiéres, PhD
Study Chair
University Medical Centre of Montpellier
Matthias Löhr, MD
Study Chair
Karolinska Institutet
Claus L Andersen, PhD
Study Director
Aarhus University Hospital

Kontakt

Studienlocations
(3 von 15)

Department of General-, Visceral- and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
20246 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Thilo Hackert, MD, MBA
Phone: +49 (0) 40 7410 - 52401
E-Mail: allgemeinchirurgie@uke.de

Nathaniel Melling, MD
Phone: +49 (0) 40 7410 - 50162
E-Mail: n.melling@uke.de» Ansprechpartner anzeigen
Brustzentrum am Universitätsklinikum Hamburg-Eppendorf
Martinistraße 52
20251 Hamburg
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Daniel J Smit, MD, PhD
Phone: +49 (0) 40 7410 - 57495
E-Mail: d.smit@uke.de» Ansprechpartner anzeigen
Abteilung für Onkologie, Medizinische Universität Graz
8010 Graz
AustriaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Armin Gerger, MD, PhD
Phone: +43-316-385-80625
E-Mail: armin.gerger@medunigraz.at» Ansprechpartner anzeigen
Herlev Hospital
2730 Herlev
DenmarkNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Mads F Klein, MD, Ph.D
E-Mail: mads.falk.klein@regionh.dk

Jeppe Kildsig, MD
E-Mail: Jeppe.Kildsig@regionh.dk» Ansprechpartner anzeigen
LCCRH (Laboratoire Cellules Circulantes Rares Humaines) - CHU de Montpellier
34295 Montpellier
FranceRekrutierend» Google-Maps
Ansprechpartner:
Catherine Alix-Panabiéres, PhD
Phone: +33 (0)4 11 75 99 31
E-Mail: c-panabieres@chu-montpellier.fr

Thomas Bardol, MD
Phone: +33 (0)4 11 75 99 31
E-Mail: t-bardol@chu-montpellier.fr» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Collection of clinical plasma samples at relevant time points (Time Frame - 8 months after end of recruitment):
For head-to-head performance assessment and benchmarking of ctDNA diagnostics



Secondary outcome:

1. The 3-year recurrence-free survival (Time Frame - 3 years after end of recruitment)

2. Lead time between ctDNA detection and clinical recurrence (Time Frame - 3 years after end of recruitment)

3. Prognostic value of ctDNA analysis at relevant time points (Time Frame - 3 years after end of recruitment)

Studien-Arme

  • Colorectal cancer stage III
  • Colorectal cancer liver metastasis

Quelle: ClinicalTrials.gov


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