Trial Title:
DANISH.MRD: Danish Assessment of Minimal Residual Disease by Liquid Biopsies
NCT ID:
NCT06076811
Condition:
Colorectal Neoplasms
Colorectal Cancer
Colorectal Adenocarcinoma
Colorectal Cancer Stage I
Colorectal Cancer Stage II
Colorectal Cancer Stage III
Conditions: Official terms:
Colorectal Neoplasms
Neoplasm, Residual
Conditions: Keywords:
Circulating tumor DNA
Surveillance
Risk stratification
Recurrence detection
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Summary:
Approximately two-thirds of all colorectal cancer patients undergo surgery with the aim
of curing them. However, despite the surgery, 20-25% of them experience relapse. It is
possible to reduce the risk of relapse with chemotherapy, but as chemotherapy is
associated with significant side effects, it is only given to patients at high risk of
relapse. Currently, the risk is assessed based on an examination of the removed tumor
tissue.
In a previous research project, blood samples were taken after patients' surgery and
examined for the presence of circulating tumor DNA (ctDNA). When cancer cells in solid
tumors die, they release DNA, which can be detected in the blood. DNA in the blood has a
half-life of less than 2 hours, so if ctDNA is found in a blood sample taken, e.g., 14
days after surgery, the patient most likely still has cancer cells in their body.
The results show that if a patient has ctDNA in their blood after surgery, the risk of
relapse is high. The presence of ctDNA in the blood has the potential to be a better
indicator of the risk of future relapse than the tumor examination used today. Therefore,
ctDNA analysis has the potential to become a marker that will be used in the future
clinical setting for monitoring colorectal cancer.
The overall objective of this study is to confirm that ctDNA found in a blood sample
after intended curative treatment for CRC is a marker of residual disease and risk of
recurrence and is applicable in clinical practice.
Detailed description:
Colorectal cancer (CRC) is the third most common cancer worldwide. Approximately 75% of
patients initially present with potentially curable disease, but despite curatively
intended treatment up to 25 % of them experience a relapse of the disease. Upon
diagnosis, survival of CRC can be improved by offering adjuvant chemotherapy to patients
with a high risk of recurrence, or by early detection of recurrence enabling early
intervention which improves patient survival significantly. To achieve this, it is
essential to have sensitive and specific tools for correctly identifying patients with a
high risk of recurrence and the need for adjuvant therapy, and for early detection of
recurrence facilitating early intervention. Non-invasive analysis of circulating tumor
DNA (ctDNA) is an emerging tool that has this potential.
Objectives
The overall objective of the study is to confirm that ctDNA detected after intended
curative treatment for CRC is a marker of residual disease and risk of recurrence and is
applicable in clinical practice.
Primary objectives
P1: To determine the prognostic value of a patient's ctDNA status and compare it with
other known prognostic factors. Specifically, the aim is to determine the association
between 3-year disease-free survival (DFS) and ctDNA detection status immediately after
1) curative-intended surgery and 2) adjuvant chemotherapy.
P2: To identify a cohort of UICC stage III CRC patients with planned adjuvant
chemotherapy. These patients will be offered enrollment in the DANISH.MRD part II
(Secondary objective 1 (S1)), and will further be included in a European collaboration
named GUIDE.MR-01-CRC, funded by the European Union via the Innovative Health Initiative.
Secondary objectives
S1: To technically assess, compare, and rank commercial ctDNA diagnostics and evaluate
their performance after intended-curative CRC treatment (postoperatively and post
adjuvant chemotherapy) to identify the best-performing method at each time point.
S2: To assess the effect of standard-of-care adjuvant chemotherapy on the level of ctDNA.
Especially, for patients with ctDNA detected after surgery, the aim is to measure and
compare the ctDNA levels in plasma samples drawn before and after adjuvant chemotherapy.
Further, the change in ctDNA level will be correlated to the oncological outcomes (time
to clinical recurrence, disease-free survival, and overall survival).
S3: To investigate if time to Molecular recurrence determined using serial ctDNA analyses
in longitudinally collected plasma samples is shorter than time to Clinical recurrence
using standard-of-care radiological imaging.
S4: To investigate the correlation between ctDNA analysis results and findings on CT
scans. ctDNA analysis will be restricted to blood sampling times that coincide with
standard-of-care CT scans (at 12 and 36 months postoperatively). If ctDNA analysis can
predict the outcome of the CT scan, the potential is that ctDNA analysis in the future
can guide when to perform CT scans.
S5: To investigate the prognostic power of ctDNA at the time point of indeterminate CT
scans.
S6: To investigate, if molecular characterization of CRC cancers can stratify patients
and predict i.e., treatment response, growth patterns, cancer aggressiveness, clinical
outcomes, and whether the tumor sheds ctDNA into the circulation.
Investigational plan
The DANISH.MRD study is logistically divided into two parts, and patients are offered
participation in each part separately. The parts are called "DANISH.MRD part I -
Surgery", and "DANISH.MRD part II - Surveillance".
In DANISH.MRD part I blood samples are collected before and after surgery. For patients
receiving neoadjuvant therapy, a blood sample will also be collected before initiation of
this treatment.
In DANISH.MRD part II blood samples are collected immediately after adjuvant chemotherapy
and during standard-of-care surveillance.
Patients included in DANISH.MRD part I will help address Primary objective 1 (P1). The
subset of the part I patients that are also included in DANISH.MRD part II will help to
address the Secondary objectives S1-S6.
Both Part I and Part II DANISH.MRD patients receive standard follow-up care, which
includes scheduled visits for up to 5 years following their surgery.
Sample collection for DANISH.MRD part I - Surgery (Objectives P1-2, S1-S5)
- Blood sampling preoperatively and after surgery (between days 20-30, but before
initiation of adjuvant chemotherapy)
- Sampling of tissue from the resected specimen
Sample collection in DANISH.MRD part II - Surveillance (objectives S1-S5)
- Blood sampling post-adjuvant chemotherapy (ACT): postACT (14-30 days after the end
of ACT), and at months 8, 12, 16, 20, 24, 30 and 36 postoperatively.
Criteria for eligibility:
Study pop:
DANISH.MRD part I - Surgery Patients with colorectal cancer clinical stage I-III
scheduled for curative-intent resectional surgery.
DANISH.MRD part I - Surveillance Patients participating in DANISH.MRD part 1, and
pathological stage III colorectal cancer, and candidates for adjuvant chemotherapy.
Sampling method:
Non-Probability Sample
Criteria:
DANISH.MRD part I - Surgery
Inclusion Criteria:
- Colon or rectal cancer, clinical tumor stage I-III.
- Patient able to understand and sign written informed consent.
- Scheduled for curative-intent resectional surgery (including "compromised" curative
resections).
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.
- Malignant colorectal polyps diagnosed after polypectomy.
- 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.
DANISH.MRD part II - Surveillance
Inclusion Criteria:
- Participation in DANISH.MRD part I - Surgery.
- Colorectal cancer, UICC stage III.
- Has received curative-intent resection and is a candidate for adjuvant chemotherapy
(3- or 6-months regime).
Exclusion Criteria:
- Not treated with adjuvant chemotherapy
- Treated with neoadjuvant chemo-radiation therapy.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
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
Start date:
August 1, 2023
Completion date:
July 30, 2030
Lead sponsor:
Agency:
University of Aarhus
Agency class:
Other
Collaborator:
Agency:
Aarhus University Hospital
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/NCT06076811
