Pancreatic Neuroendocrine TumorFORESEENCT06406387
ATRX/DAXX in EUS-FNB Specimens of Pan-NETs
An observational study of Pancreatic Neuroendocrine Tumor, run by Azienda Ospedaliera Universitaria Integrata Verona at 1 site in Italy.
Trial summary
P-NENs are classified as functional (F-) or non-functional (NF-) depending on the presence or absence of a clinical hormonal hypersecretion syndrome. Moreover, the WHO 2017 classification of pNENs distinguishes between well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly differentiated pancreatic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neuroendocrine Tumor
- What is being tested?
- ATRX/DAXX immunohistochemistry
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2024to 30 Nov 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Patients with a diagnosis of pancreatic neuroendocrine tumors
Who may be able to join
- Age ≥18 years
- Cyto/histologic diagnosis of pNETs
- Signed informed consent
Who cannot join
- Functional pNETs
- Multiple pancreatic nodules
- Diagnosis of MEN-1 or Von-Hippel Lindau
- Mixed types (e.g., mixed neuroendocrine-acinar/adenocarcinoma) or neuroendocrine carcinomas
- Predominantly cystic lesions (more than 50% of the volume).
- Metastatic tumors at the time of diagnosis
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- Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma
- Use of anticoagulants that cannot be discontinued
- INR >1.5 or platelet count <50.000
- Pregnancy or breastfeeding
- Failure to sign the patient's or closest relative's informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Association Between Endoscopic Ultrasound Based Preoperative ATRX/DAXX Immunohistochemistry Expression and Prognosis of Sporadic, Non-FunctiOnal pancREatic Neuroendocrine tumorS: a prospEctivE Cohort Study
P-NENs are classified as functional (F-) or non-functional (NF-) depending on the presence or absence of a clinical hormonal hypersecretion syndrome. Moreover, the WHO 2017 classification of pNENs distinguishes between well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs). pNETs are then divided according to a grading scheme based on Ki67 index in pNETs-G1 (Ki67 index ≤3%) and pNETs-G2 (Ki67 index between 4% and 20%). pNECs are all G3, with a Ki67 index >20%. Endoscopic ultrasound with fine-needle biopsy (EUS-FNB) demonstrated safe and effective preoperative grading based on the Ki-67 proliferative index. However, downstaging rate is not neglectable, reaching 15% in a recent metanalysis. Moreover, recent whole-exome and whole genome sequencing studies revealed that the mutually exclusive inactivating mutations in death domain-associated protein (DAXX) and/or in α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes are associated with more aggressive disease. In a retrospective study, the investigators recently evaluated the correspondence of DAXX/ATRX expression on 41 EUS-FNB samples with corresponding surgical specimens demonstrating a 95.1% (almost perfect agreement, κ = 0.828; p < 0.001) and 92.7% (substantial agreement, κ = 0.626; p < 0.001) concordance for DAXX and ATRX expression, respectively. This study aims to evaluate the potential clinical/prognostic role of DAXX/ATRX expression as implementation of the currently used Ki67-based grading, evaluated on EUS-FNB samples in a prospective cohort of patients with NF-pNETs
- Conditions
- Pancreatic Neuroendocrine Tumor
- Being tested
- ATRX/DAXX immunohistochemistry
- Medical subject headings
- Adenoma, Islet Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATRX/DAXX immunohistochemistryDiagnostic test
Immunohistochemistry will be performed using an Autostainer Leica (Leica Biosystems) according to the manufacturer's instructions. Four μm formalin-fixed paraffin-embedded sections will be immunostained with antibodies for Cytokeratin AE1/AE3 (AE1-AE3, 1:100 dilution, Novocastra/United Kingdom) Chromogranin A (DAK-A3, 1:2500, Dako/Denmark), and Synaptophysin (27G12, 1:100, Novocastra), Ki67 (MIB1, 1:100, Dako/Denmark), ATRX (1:400, Sigma-Aldrich), DAXX (1:200, Sigma-Aldrich). After antigen retrieval, immunostaining will be performed in an automated Bond instrument (Vision-Biosystem, Leica, Milan, Italy) using a sensitive peroxidase-based 'Bond polymer Refine' detection system.
| Study group | Role | What they receive |
|---|---|---|
| ATRX/DAXX loss | The "positive" group including patients with loss of DAXX or ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens Receives: Diagnostic Test: ATRX/DAXX immunohistochemistry | |
| ATRX/DAXX preserved | The "negative" group including those with preserved DAXX and ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens Receives: Diagnostic Test: ATRX/DAXX immunohistochemistry |
What is being measured
The primary outcome is the main question the study is designed to answer.
ATRX/DAXX loss-tumor aggressiveness association
To assess the association between ATRX/DAXX loss of expression assessed on endoscopic ultrasound biopsy specimens and pathological features indicative of tumor aggressiveness evaluated on surgical pathology
Measured: 18 months
Secondary outcomes (4)
Ki-67 concordance
To evaluate the concordance rate of Ki67-based tumor grade between endoscopic ultrasound biopsy samples and surgical specimens.
Measured: 18 months
DAXX/ATRX concordance
To evaluate the concordance rate of DAXX/ATRX expression between endoscopic ultrasound biopsy samples and surgical specimens
Measured: 18 months
Ki-67-tumor aggressiveness association
To assess the association between preoperative Ki67-based grade 2/3 on endoscopic ultrasound samples and pathological features indicative of tumor aggressiveness evaluated on surgical pathology
Measured: 18 months
Preoperative prognosis assessment
To evaluate the association between DAXX/ATRX expression on endoscopic ultrasound biopsy samples, Ki67-based grade 2/3 on endoscopic ultrasound biopsy samples, and tumor size on endoscopic ultrasound and progression-free survival and relapse-free survival.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2024
- Study start1 Jun 2024
- Primary completion30 Mar 2025
- Study completion30 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Neuroendocrine TumorStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera Universitaria Integrata Verona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06406387
- Sponsor's protocol ID
- FORESEE
- Acronym
- FORESEE
- Status last verified
- Jan 2025
- First submitted
- 6 May 2024
- Last updated
- 13 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between Endoscopic Ultrasound Based Preoperative ATRX/DAXX Immunohistochemistry Expression and Prognosis of Sporadic, Non-FunctiOnal pancREatic Neuroendocrine tumorS: a prospEctivE Cohort Study
- ClinicalTrials.gov ID
- NCT06406387
- Acronym / sponsor ID
- FORESEE / FORESEE
- Conditions
- Pancreatic Neuroendocrine Tumor
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Azienda Ospedaliera Universitaria Integrata VeronaUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 30 Mar 2025 (actual)
- Study completion
- 30 Nov 2029 (estimated)
- First posted
- 9 May 2024 (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.
P-NENs are classified as functional (F-) or non-functional (NF-) depending on the presence or absence of a clinical hormonal hypersecretion syndrome. Moreover, the WHO 2017 classification of pNENs distinguishes between well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs). pNETs are then divided according to a grading scheme based on Ki67 index in pNETs-G1 (Ki67 index ≤3%) and pNETs-G2 (Ki67 index between 4% and 20%). pNECs are all G3, with a Ki67 index >20%. Endoscopic ultrasound with fine-needle biopsy (EUS-FNB) demonstrated safe and effective preoperative grading based on the Ki-67 proliferative index. However, downstaging rate is not neglectable, reaching 15% in a recent metanalysis. Moreover, recent whole-exome and whole genome sequencing studies revealed that the mutually exclusive inactivating mutations in death domain-associated protein (DAXX) and/or in α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes are associated with more aggressive disease. In a retrospective study, the investigators recently evaluated the correspondence of DAXX/ATRX expression on 41 EUS-FNB samples with corresponding surgical specimens demonstrating a 95.1% (almost perfect agreement, κ = 0.828; p < 0.001) and 92.7% (substantial agreement, κ = 0.626; p < 0.001) concordance for DAXX and ATRX expression, respectively. This study aims to evaluate the potential clinical/prognostic role of DAXX/ATRX expression as implementation of the currently used Ki67-based grading, evaluated on EUS-FNB samples in a prospective cohort of patients with NF-pNETs
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATRX/DAXX loss | – | Diagnostic Test: ATRX/DAXX immunohistochemistryThe "positive" group including patients with loss of DAXX or ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens |
| ATRX/DAXX preserved | – | Diagnostic Test: ATRX/DAXX immunohistochemistryThe "negative" group including those with preserved DAXX and ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a diagnosis of pancreatic neuroendocrine tumors
Key inclusion criteria (3 listed)
- Age ≥18 years
- Cyto/histologic diagnosis of pNETs
- Signed informed consent
Key exclusion criteria (11 listed)
- Functional pNETs
- Multiple pancreatic nodules
- Diagnosis of MEN-1 or Von-Hippel Lindau
- Mixed types (e.g., mixed neuroendocrine-acinar/adenocarcinoma) or neuroendocrine carcinomas
- Predominantly cystic lesions (more than 50% of the volume).
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 |
|---|---|---|
| ATRX/DAXX immunohistochemistryImmunohistochemistry will be performed using an Autostainer Leica (Leica Biosystems) according to the manufacturer's instructions. Four μm formalin-fixed paraffin-embedded sections will be immunostained with antibodies for Cytokeratin AE1/AE3 (AE1-AE3, 1:100 dilution, Novocastra/United Kingdom) Chromogranin A (DAK-A3, 1:2500, Dako/Denmark), and Synaptophysin (27G12, 1:100, Novocastra), Ki67 (MIB1, 1:100, Dako/Denmark), ATRX (1:400, Sigma-Aldrich), DAXX (1:200, Sigma-Aldrich). After antigen retrieval, immunostaining will be performed in an automated Bond instrument (Vision-Biosystem, Leica, Milan, Italy) using a sensitive peroxidase-based 'Bond polymer Refine' detection system. | Diagnostic test | ATRX/DAXX loss, ATRX/DAXX preserved |
Primary outcome
ATRX/DAXX loss-tumor aggressiveness association
Time frame: 18 months
To assess the association between ATRX/DAXX loss of expression assessed on endoscopic ultrasound biopsy specimens and pathological features indicative of tumor aggressiveness evaluated on surgical pathology
4 secondary outcomes
Ki-67 concordance
Time frame: 18 months
DAXX/ATRX concordance
Time frame: 18 months
Ki-67-tumor aggressiveness association
Time frame: 18 months
Preoperative prognosis assessment
Time frame: 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
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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?
An observational study of Pancreatic Neuroendocrine Tumor, run by Azienda Ospedaliera Universitaria Integrata Verona at 1 site in Italy.
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 11 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: under way, not looking for participants, as of the sponsor's last update on 13 Jan 2026. 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
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?
ATRX/DAXX loss-tumor aggressiveness association (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2026.