To establish the diagnostic and predictive value of different biomarkers in patients with pancreatic cancer by the investigation of:- Mutated ct-DNA levels in pancreatic juice and blood.- Chromosomal instability in pancreatic juice and blood.- Pro-…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter: CtDNA levels in pancreatic juice and blood in relation to
(progression-free) survival.
Secondary outcome
Secondary study parameters (in patients undergoing EUS or ERCP for (suspected)
PC)
- CtDNA levels in pancreatic juice and blood.
- CINdex in pancreatic juice and blood.
- The cellular composition of pancreatic juice: number of cancer cells,
clonality of the cancer cells, intracellular (single-cell) mutations (e.g.
KRAS, CDKN2A, SMAD-4, TP53), the capability to grow organoids.
- Molecular composition of pancreatic juice and blood: levels of pro- and
anti-inflammatory molecules, levels and function of inhibitory and activating
immune cells, levels of molecules related to fibrosis.
- (Progression free) survival (assessed after 12 and 18 months) based on
morphology on MRI and EUS.
- Tumour size.
- Presence of metastases.
Background summary
The incidence of pancreatic cancer (PC) in the Netherlands is low, yet the
prognosis is dismal. In 2030, PC is even expected to be the number one cause of
cancer related death, worldwide. At present, PC diagnosis is based on imaging,
yet the development of biomarkers is needed, not only to enable timely
detection, but also to allow personalized care and early prediction of
treatment response. Individual biomarkers seem to have a limited predictive
value. A broad approach is needed, investigating different molecular markers in
different biomaterials (pancreatic juice and blood) to develop a combination of
tests that will improve PC survival. We expect to detect cellular and
extra-cellular (ct-DNA, cytokines, fibrotic mediators) components of the tumour
in pancreatic juice and blood, serving as promising targets for biomarker
detection.
Study objective
To establish the diagnostic and predictive value of different biomarkers in
patients with pancreatic cancer by the investigation of:
- Mutated ct-DNA levels in pancreatic juice and blood.
- Chromosomal instability in pancreatic juice and blood.
- Pro- and anti-inflammatory molecules in pancreatic juice, tumour specimens
and blood.
- Fibrotic mediators in pancreatic juice and tumour specimens.
Secondary objectives:
- To evaluate the cellular compartment of pancreatic juice from PC patients and
the ability to grow organoids from it.
Study design
This is a single-centre prospective study, performed in 200 patients undergoing
EUS or ERCP for (suspected) PC. Molecular and cellular compartments of
pancreatic juice, blood-derived materials (serum and plasma) and tumour tissue
will be related to cancer presence, tumour size, the presence of metastases and
survival. Additionally, patients with PC will be compared with patients
undergoing EUS or ERCP for (suspected) pancreatitis, neuro-endocrine tumour or
a non-pancreatic reason (e.g. choledocholithiasis). Furthermore, organoids will
be grown from cancer-cells extracted from pancreatic juice and tissue.
*
Study burden and risks
The burden will consist of one blood collection from the drip per endoscopic
ultrasound or ERCP. In addition, secretin will be administered intravenously
during the procedure, to promote wash-out of pancreatic juice per endoscopic
ultrasound or ERCP.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
Patients with (suspected) pancreatic tumour, chronic pancreatitis and healthy
controls (non-pancreatic non-healthy) that undergo an endoscopic ultrasound or
ERCP.
The latter group is defined as all individuals undergoing endoscopic ultrasound
or ERCP for a non-pancreatic indication (e.g. choledocholithiasis), individuals
with a personal history with pancreatic disease (including pancreatic cysts,
pancreatitis or any other pancreas-related disease, post-surgery) or autoimmune
disease will not be included in this group. In addition, patients with a
history of malignancy could only be included if they have been treated
curatively >5 years ago.
Exclusion criteria
Age < 18 years.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL64724.078.18 |
| OMON | NL-OMON25284 |