Pancreatic CystNCT03578445
Utility of EUS-guided Microbiopsies in Pancreatic Cystic Lesions
A study testing EUS-guided microbiopsy and Next Generation Sequencing in people with Pancreatic Cyst and IPMN, run by Herlev Hospital at 1 site in Denmark.
Trial summary
The purpose of this study is to determine clinical impact of EUS-guided microbiopsy procedure and supplementary molecular analyses compared to standard diagnostic workup of pancreatic cysts. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cyst, IPMN, Mucinous Cyst
- What is being tested?
- EUS-guided microbiopsy and Next Generation Sequencing
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2018to 31 Aug 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years old or above
- Able to provide informed consent
- Pancreatic cyst with a diameter of 15 mm or above OR pancreatic cyst of any size with any one of either high-risk stigmata or worrisome features (obstructive jaundice in patients with a cyst in the head of the pancreas, solid component/mural nodule, thickened/enhancing cyst wall, main pancreatic duct ≥ 10 mm or abrupt change of main pancreatic duct diameter with distal atrophy)
Who cannot join
- Lactating and pregnant females
- Cystic lesions with a predominantly solid component, suspected of malignancy
- Patients with uncorrected coagulopathy (international normalized ratio > 1.5 or platelet count < 50 109/L)
- Patients with previous history of pancreatic cancer
- Patients with a history of major stomach surgery (e.g. Billroth 1 and 2, gastrectomy, gastric bypass, esophagectomy, resection of the liver or pancreas)
- Patients with disseminated malignant disease
Show all 10Show fewer
- Patients unfit for surgery
- Patients where EUS-guided puncture of the lesion is not presumed technically feasible and/or safe
- Patients with systemic immunosuppressive disease or receiving systemic immunosuppressive treatment
- Patients with a history of recent pancreatitis (within 3 months)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Utility of EUS-guided Microbiopsies Combined With Auxiliary Molecular Techniques in the Workup of Pancreatic Cystic Lesions
The purpose of this study is to determine clinical impact of EUS-guided microbiopsy procedure and supplementary molecular analyses compared to standard diagnostic workup of pancreatic cysts. The hypothesis is that a combination of previously mentioned modalities may change the management of some pancreatic cystic lesions, increase the diagnostic accuracy and optimize the discrimination between high- and low-risk pancreatic cysts.
Read the detailed description
Pancreatic ductal adenocarcinoma (PDAC) accounts for 6% of all cancer related deaths in Denmark, and the 5-year survival rate is only 8%. PDAC develops from precursor lesions with pancreatic intraepithelial neoplasia (panIN) being the most common, and cystic lesions as a second precursor. Unlike panINs, which are too small for detection with current imaging modalities, cystic lesions of the pancreas are increasingly diagnosed due to the extended use of cross-sectional imaging. Pancreatic cystic lesions may be observed in up to 13.5% of all MRI scans and 3% of all CT scans. There are several types of pancreatic cysts and each of them requires individual management, ranging from no treatment over watchful waiting to surgical resection according to their malignant potential.
Standard diagnostic workup includes cross-sectional imaging of the cystic lesions and, in selected cases endoscopic ultrasound (EUS) with aspiration of cyst fluid by fine needle aspiration (FNA), followed by cyst fluid cytology and tumor marker analysis. The diagnostic algorithm is based on International consensus guidelines established in 2006, and revised in 2012 and 2017, integrating clinical features with EUS-findings. The level of evidence in these guidelines is unfortunately low. A recent meta-analysis concluded that EUS and cyst fluid cytology have low sensitivity (54-63%), whereas the specificity is acceptable (88-92%) for detection of mucinous cysts. Low sensitivity is mainly due to absence of sufficient cellular material in the cyst fluid for definite diagnosis. Tumor marker analysis of cyst fluid, such as carcinoembryonic antigen (CEA), CA 72.4, CA 125, CA 19.9, and CA 15.3, have been studied extensively with CEA being the most accurate marker. A cut-off value of 192 ng/mL for CEA distinguishes mucinous from non-mucinous cysts with a good, albeit imperfect, accuracy of 80%. However, the value will not differentiate between IPMN and MCN, and more importantly, it does not correlate with the level of dysplasia or malignancy.
EUS-guided through-the-needle microbiopsy using the Moray™ forceps is a novel adjunctive. The device can be inserted through a EUS-FNA needle and used to obtain microbiopsies from different tissues in relationship to the gastrointestinal system. This instrument can be used in combination with EUS-FNA to subsequently obtain microbiopsies from the pancreatic cyst wall. Microbiopsies seem to represent a break-through in pre-operative classification of pancreatic cysts, as they provide histological material for examination of tissue architecture not readily accessible in FNA material. However, very little experience has been obtained hitherto. Even though this technique is currently described only in a few studies, it seems feasible and theoretically offers a higher quality of material than what can be obtained by EUS-FNA alone.
- Conditions
- Pancreatic Cyst, IPMN, Mucinous Cyst, Pancreatic Adenocarcinoma
- Being tested
- EUS-guided microbiopsy, Next Generation Sequencing
- Keywords
- EUS, EUS-FNA, microbiopsy
- Medical subject headings
- Pancreatic Cyst, Mucocele
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EUS-guided microbiopsyDevice
Also called Moray
Use of EUS-guided through-the-needle microbiopsy forceps for obtainment of tissue from the wall of the cystic lesion
Next Generation SequencingDiagnostic test
Also called NGS
Prevalence of genetic mutations in known cancer-associated genes in the microbiopsy tissue examined using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, USA). The multigene panel explores selected regions of 50 cancer-associated genes, among others KRAS, GNAS, CDKN2A and SMAD4 genes.
| Study group | Role | What they receive |
|---|---|---|
| Patients with a pancreatic cystic lesion | Experimental | Not described Receives: Device: EUS-guided microbiopsy; Diagnostic Test: Next Generation Sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical impact of EUS-guided microbiopsies in patients with pancreatic cystic lesions
All patients are evaluated at a multidisciplinary conference prior to microbiopsy procedure. A primary decision is made based on available imaging modalities and/or cyst fluid analysis (operation, follow-up or discontinuation from follow-up). Subsequently, each patient is once again evaluated at a multidisciplinary conference, and a possible change in management is noted. Clinical impact is defined as a proportion of the patients where a change in clinical management is observed.
Measured: 3 weeks
Secondary outcomes (5)
Technical success of EUS-guided microbiopsy procedure
Technical success is defined as a proportion of patients where a pancreatic cystic lesion is successfully punctured by a 19G FNA needle, and where at least one microbiopsy is obtained with the microbiopsy forceps.
Measured: 3 weeks
Adverse events following EUS-guided microbiopsy procedure
Adverse events are defined in concordance with ASGE guidelines (Cotton PB, Eisen GM, Aabakken L et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454). All patients are contacted by telephone on day 3 following the procedure. Adverse event rate is an overall proportion of the patients where an adverse event is observed.
Measured: 3 weeks
Diagnostic yield of EUS-guided microbiopsies
Diagnostic yield is defined as a proportion of the patients included where a definite histopathological diagnosis could be made on microbiopsy material.
Measured: 3 weeks
Diagnostic performance of EUS-guided microbiopsies in the surgical subcohort
Sensitivity, specificity as well as positive and negative predictive values are calculated by comparing microbiopsy diagnosis with gold standard (resected specimens).
Measured: 2 years
Diagnostic values of gene mutations (NGS analyses) in microbiopsy material in the surgical subcohort
Sensitivity, specificity as well as positive and negative predictive values are calculated by correlating different mutations with final diagnosis in patients that undergo surgery. NGS analysis is performed using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, USA). The multigene panel explores selected regions of 50 cancer-associated genes, among others KRAS, GNAS, CDKN2A and SMAD4 genes.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2018
- Study start1 Feb 2018
- Primary completion31 Aug 2019
- Study completion31 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CystStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Principal investigator, Bojan Kovacevic, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03578445
- Sponsor's protocol ID
- H-17031060
- Status last verified
- Dec 2019
- First submitted
- 28 May 2018
- Last updated
- 9 Dec 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rift CV, Melchior LC, Kovacevic B, Klausen P, Toxvaerd A, Grossjohann H, Karstensen JG, Brink L, Hassan H, Kalaitzakis E, Storkholm J, Scheie D, Hansen CP, Lund EL, Vilmann P, Hasselby JP. Targeted next-generation sequencing of EUS-guided through-the-needle-biopsy sampling from pancreatic cystic lesions. Gastrointest Endosc. 2023 Jan;97(1):50-58.e4. doi: 10.1016/j.gie.2022.08.008. Epub 2022 Aug 12.
PubMed 35964683
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Utility of EUS-guided Microbiopsies Combined With Auxiliary Molecular Techniques in the Workup of Pancreatic Cystic Lesions
- ClinicalTrials.gov ID
- NCT03578445
- Acronym / sponsor ID
- H-17031060
- Conditions
- Pancreatic Cyst, IPMN, Mucinous Cyst, Pancreatic Adenocarcinoma
- Keywords
- EUS, EUS-FNA, microbiopsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 31 Aug 2019 (actual)
- First posted
- 6 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine clinical impact of EUS-guided microbiopsy procedure and supplementary molecular analyses compared to standard diagnostic workup of pancreatic cysts. The hypothesis is that a combination of previously mentioned modalities may change the management of some pancreatic cystic lesions, increase the diagnostic accuracy and optimize the discrimination between high- and low-risk pancreatic cysts.
Detailed description
Pancreatic ductal adenocarcinoma (PDAC) accounts for 6% of all cancer related deaths in Denmark, and the 5-year survival rate is only 8%. PDAC develops from precursor lesions with pancreatic intraepithelial neoplasia (panIN) being the most common, and cystic lesions as a second precursor. Unlike panINs, which are too small for detection with current imaging modalities, cystic lesions of the pancreas are increasingly diagnosed due to the extended use of cross-sectional imaging. Pancreatic cystic lesions may be observed in up to 13.5% of all MRI scans and 3% of all CT scans. There are several types of pancreatic cysts and each of them requires individual management, ranging from no treatment over watchful waiting to surgical resection according to their malignant potential.
Standard diagnostic workup includes cross-sectional imaging of the cystic lesions and, in selected cases endoscopic ultrasound (EUS) with aspiration of cyst fluid by fine needle aspiration (FNA), followed by cyst fluid cytology and tumor marker analysis. The diagnostic algorithm is based on International consensus guidelines established in 2006, and revised in 2012 and 2017, integrating clinical features with EUS-findings. The level of evidence in these guidelines is unfortunately low. A recent meta-analysis concluded that EUS and cyst fluid cytology have low sensitivity (54-63%), whereas the specificity is acceptable (88-92%) for detection of mucinous cysts. Low sensitivity is mainly due to absence of sufficient cellular material in the cyst fluid for definite diagnosis. Tumor marker analysis of cyst fluid, such as carcinoembryonic antigen (CEA), CA 72.4, CA 125, CA 19.9, and CA 15.3, have been studied extensively with CEA being the most accurate marker. A cut-off value of 192 ng/mL for CEA distinguishes mucinous from non-mucinous cysts with a good, albeit imperfect, accuracy of 80%. However, the value will not differentiate between IPMN and MCN, and more importantly, it does not correlate with the level of dysplasia or malignancy.
EUS-guided through-the-needle microbiopsy using the Moray™ forceps is a novel adjunctive. The device can be inserted through a EUS-FNA needle and used to obtain microbiopsies from different tissues in relationship to the gastrointestinal system. This instrument can be used in combination with EUS-FNA to subsequently obtain microbiopsies from the pancreatic cyst wall. Microbiopsies seem to represent a break-through in pre-operative classification of pancreatic cysts, as they provide histological material for examination of tissue architecture not readily accessible in FNA material. However, very little experience has been obtained hitherto. Even though this technique is currently described only in a few studies, it seems feasible and theoretically offers a higher quality of material than what can be obtained by EUS-FNA alone.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with a pancreatic cystic lesion | Experimental | Device: EUS-guided microbiopsy, Diagnostic Test: Next Generation Sequencing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients 18 years old or above
- Able to provide informed consent
- Pancreatic cyst with a diameter of 15 mm or above OR pancreatic cyst of any size with any one of either high-risk stigmata or worrisome features (obstructive jaundice in patients with a cyst in the head of the pancreas, solid component/mural nodule, thickened/enhancing cyst wall, main pancreatic duct ≥ 10 mm or abrupt change of main pancreatic duct diameter with distal atrophy)
Key exclusion criteria (10 listed)
- Lactating and pregnant females
- Cystic lesions with a predominantly solid component, suspected of malignancy
- Patients with uncorrected coagulopathy (international normalized ratio > 1.5 or platelet count < 50 109/L)
- Patients with previous history of pancreatic cancer
- Patients with a history of major stomach surgery (e.g. Billroth 1 and 2, gastrectomy, gastric bypass, esophagectomy, resection of the liver or pancreas)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EUS-guided microbiopsyAlso: MorayUse of EUS-guided through-the-needle microbiopsy forceps for obtainment of tissue from the wall of the cystic lesion | Device | Patients with a pancreatic cystic lesion |
| Next Generation SequencingAlso: NGSPrevalence of genetic mutations in known cancer-associated genes in the microbiopsy tissue examined using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, USA). The multigene panel explores selected regions of 50 cancer-associated genes, among others KRAS, GNAS, CDKN2A and SMAD4 genes. | Diagnostic test | Patients with a pancreatic cystic lesion |
Primary outcome
Clinical impact of EUS-guided microbiopsies in patients with pancreatic cystic lesions
Time frame: 3 weeks
All patients are evaluated at a multidisciplinary conference prior to microbiopsy procedure. A primary decision is made based on available imaging modalities and/or cyst fluid analysis (operation, follow-up or discontinuation from follow-up). Subsequently, each patient is once again evaluated at a multidisciplinary conference, and a possible change in management is noted. Clinical impact is defined as a proportion of the patients where a change in clinical management is observed.
5 secondary outcomes
Technical success of EUS-guided microbiopsy procedure
Time frame: 3 weeks
Adverse events following EUS-guided microbiopsy procedure
Time frame: 3 weeks
Diagnostic yield of EUS-guided microbiopsies
Time frame: 3 weeks
Diagnostic performance of EUS-guided microbiopsies in the surgical subcohort
Time frame: 2 years
Diagnostic values of gene mutations (NGS analyses) in microbiopsy material in the surgical subcohort
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Derived from this study: PubMed 35964683Rift CV, Melchior LC, Kovacevic B, Klausen P, Toxvaerd A, Grossjohann H, Karstensen JG, Brink L, Hassan H, Kalaitzakis E, Storkholm J, Scheie D, Hansen CP, Lund EL, Vilmann P, Hasselby JP. Targeted next-generation sequencing of EUS-guided through-the-needle-biopsy sampling from pancreatic cystic lesions. Gastrointest Endosc. 2023 Jan;97(1):50-58.e4. doi: 10.1016/j.gie.2022.08.008. Epub 2022 Aug 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EUS-guided microbiopsy and Next Generation Sequencing in people with Pancreatic Cyst and IPMN, run by Herlev Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical impact of EUS-guided microbiopsies in patients with pancreatic cystic lesions (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03578445, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.