Aspiration of duodenopancreatic juice after secretin stimulation (ADPJsecr-) vs endoscopic aspiration (EUS-FNA) for molecular analysis of intraductal papillary mucinous intraductal neoplasia (IPMN).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Decision date (initial)

2025-01-14

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-519972-21-00

EudraCT number

2022-002764-79

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To compare the detection rate of somatic mutations in GNAS and KRAS in liquid samples obtained by the techniques under study (ADPJ-secr and EUS-FNA) in patients with MPIN.

Secondary objectives 16

1. Compare the detection rate of somatic mutations in Tp53 in samples obtained by the 2 techniques (AJPDsec and EUS-FNA) in the subgroup of patients with IPMN who underwent pancreatic resection within 12 months of study entry.
2. Compare the concentration of DNA obtained by both study techniques (AJPDsec and EUS-FNA).
3. Compare the quality of DNA obtained by both techniques (AJPDsec and EUS-FNA).
4. To compare the sensitivity between the two techniques under study (AJPDsec and EUS-FNA) for the diagnosis of intraductal papillary mucinous neoplasms (IPMN) in the subgroup of patients undergoing pancreatic resection within 12 months after inclusion in the study.
5. To compare the specificity between the two techniques under study (AJPDsec and EUS-FNA) for the diagnosis of intraductal papillary mucinous neoplasms (IPMN) in the subgroup of patients undergoing pancreatic resection within 12 months after inclusion in the study.
6. To compare the positive predictive value of malignancy of Tp53 mutations between the two techniques under study (AJPD-sec and EUS-FNA) in the subgroup of patients undergoing pancreatic resection within 12 months after inclusion in the study.
7. To compare the negative predictive value of malignancy of the absence of Tp53 mutations between the two techniques under study (AJPD-sec and EUS-FNA) in the subgroup of patients undergoing pancreatic resection within 12 months after inclusion in the study.
8. To correlate the mutational profile with the patient's clinical-epidemiological data.
9. To correlate the mutational profile with the morphological characteristics of the lesion obtained by EUS.
10. To correlate the mutational profile with the technical characteristics of EUS-FNA and AJPD-sec.
11. To correlate the mutational profile with macroscopic data of the intracystic fluid.
12. To correlate the mutational profile with biochemical data of the intracystic fluid.
13. To correlate the mutational profile with cytological data of the intracystic fluid.
14. To evaluate the feasibility of AJPD-sec using a gastroscope with a cap without the need for rescue with a duodenoscope.
15. To evaluate the incidence of adverse effects related to both techniques.
16. To evaluate the incidence of serious adverse events at 24 hours and 7 days after the procedures under study.

Conditions and MedDRA coding

Pancreatic cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Be a man or woman over 18 years of age.
2. 2. Willing to comply with the study procedures described in the protocol.
3. 3. Willing and able to give written informed consent.
4. 4. Meeting at least one of the following three criteria related to the diagnosis or prognosis of IPMN: 4.1. Diagnosis of IPMN based on evidence of the major criterion or the presence of at least 2 minor criteria. -Major criterion: Characteristic imaging on MRI and/or EUS (single or multiple cysts with clear ductal communication and/or focal or diffuse dilation ≥ 5 mm in diameter of the main pancreatic duct without apparent obstructive cause). -Minor criteria: a) Mucus-secreting cells and/or extracellular mucin in the cytological examination of intracystic fluid. b) Clearly mucoid or filamentous appearance of the intracystic fluid. c) CEA concentration in intracystic fluid >192 ng/mL or intracystic glucose < 50 mg/dL.
5. 4.2. IPMN with cysts with a diameter ≥ 10 mm and/or focal or diffuse dilatation of the main pancreatic duct with a diameter ≥ 7 mm requiring EUS-FNA for diagnostic purposes or to assess risk or existence of malignancy following the main clinical practice guidelines.
6. 4.3. IPMN with indication for surgical resection of the lesion.
7. 5. If the participant is a woman of childbearing potential, she must be willing to use highly effective contraceptive methods or practice sexual abstinence from the screening visit until one week after undergoing the procedure under study. Highly effective contraceptive methods include: combined (containing estrogen and progestogen) oral, intravaginal, or transdermal hormonal contraception associated with ovulation inhibition; progestogen-only oral, injectable, or implantable hormonal contraception associated with ovulation inhibition; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized partner; and sexual abstinence.
8. 6. If the participant is a woman of reproductive age, she must be willing to undergo a urine pregnancy test prior to inclusion in the study.

Exclusion criteria 7

1. History of surgery that prevents endoscopic access to the ampulla of Vater in the case of AJPD-sec, or to the area of the stomach or intestine from which to perform FNA.
2. Acute pancreatitis within the 30 days prior to inclusion.
3. Pregnant women, women with the possibility of pregnancy during the month prior to inclusion, or women who are breastfeeding.
4. Coagulopathy (PT < 25%, INR > 1.5, platelets < 50,000/mL) preventing FNA.
5. Renal failure with GFR < 30 mL/min or patients on dialysis.
6. Known hypersensitivity to any component of the ChiRhoStim® (human secretin) formulation.
7. Any clinically relevant medical condition that, in the opinion of the investigator, makes the patient unfit to participate in the study (underlying haematological disorders, autoimmune disease, immunodeficiency, gastrointestinal, psychiatric, renal, hepatic and cardiopulmonary disorders).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with IPMN with GNAS and KRAS mutations in intracystic fluid obtained by EUS-FNA versus pancreatic juice obtained by ADPJ-secr after both techniques.

Secondary endpoints 19

1. 1. Proportion of patients with IPMN with Tp53 mutations in samples obtained by EUS-FNA versus AJPD-sec after performing both techniques, in the subgroup of patients undergoing pancreatic resection within 12 months after inclusion in the study.
2. 2. DNA concentration expressed in ng/μl in samples obtained by EUSFNA versus ADPJ-secr after performing both techniques.
3. 3. Proportion of suitable samples obtained by the two techniques under study (ADPJ-secr and EUS-FNA) for molecular analysis. * A sample is defined as suitable when it is read by the Qubit fluorometer, which only detects full double-stranded DNA suitable for molecular analysis.
4. 4. Proportion of patients undergoing pancreatic resection with a pathological diagnosis of IPMN who have mutations in GNAS and/or KRAS in samples obtained by EUS-FNA versus ADPJ-secr within 12 months of study entry.
5. 5. Proportion of patients undergoing pancreatic resection without a pathological diagnosis of IPMN who do not have GNAS and/or KRAS mutations in samples obtained by EUS-FNA versus ADPJ-secr within 12 months of study entry.
6. 6. Proportion of patients undergoing pancreatic resection with Tp53 mutations in samples obtained by both techniques under study (ADPJsecr vs EUS-FNA) who have advanced neoplasia in the surgical resection specimen after surgery performed within 12 months after study inclusion.
7. 7. Proportion of patients undergoing pancreatic resection without Tp53 mutations in samples obtained by both techniques under study (ADPJsecr vs EUS-FNA) who do not have advanced neoplasia in the surgical resection specimen after surgery performed within 12 months after inclusion in the study.
8. 8.1. To evaluate the association between mutational status (GNAS/KRAS mutated versus GNAS/KRAS non-mutated [wild type]) in samples obtained by both techniques under study (EUS-FNA vs AJPD-sec) in relation to the following clinical-analytical variables: age, sex, toxic habits (smoking, chronic alcohol consumption)
9. 8.2. Comorbidities, history of acute pancreatitis, previous diagnosis of chronic pancreatitis, first-degree family history of pancreatic cancer, duration since IPMN diagnosis, morphological type of IPMN (IPMN-MC, IPMN-MP, mixed IPMN), blood levels of amylase, lipase, creatinine, total bilirubin, AST/ALT, GGT/ALP, creatinine, hemoglobin, platelets, CA 19-9, CEA, and glycated hemoglobin.
10. 9. To evaluate the association between mutational status in samples obtained by both techniques under study in relation to the following morphological characteristics of the lesion obtained by EUS: diameter of the largest cystic lesion, maximum diameter of the main pancreatic duct, type of pancreatic duct dilation, lesion location, presence of cystic lesion, mural nodules, signs of chronic pancreatitis, intraductal calcifications, pancreatic atrophy, and final EUS diagnosis of the lesion.
11. 10. To evaluate the association between mutational status in samples obtained by both techniques under study in relation to the following technical characteristics of EUS-FNA and AJPD-sec: access route for FNA, punctured lesion, location of the punctured lesion, needle gauge used, type of needle used, number of passes, amount of fluid obtained by both techniques, type of endoscope used for AJPD-sec.
12. 11. To evaluate the association between mutational status (GNAS/KRAS mutated versus GNAS/KRAS non-mutated [wild type]) in samples obtained by both techniques under study (EUS-FNA vs AJPD-sec) in relation to the following morphological characteristics of the intracystic fluid: filamentous or non-filamentous.
13. 12. To evaluate the association between mutational status (GNAS/KRAS mutated versus GNAS/KRAS non-mutated [wild type]) in samples obtained by both techniques under study (EUS-FNA vs AJPD-sec) in relation to the following biochemical characteristics: CEA, glucose, and amylase.
14. 13. To evaluate the association between mutational status (GNAS/KRAS mutated versus GNAS/KRAS non-mutated [wild type]) in samples obtained by both techniques under study (EUS-FNA vs AJPD-sec) in relation to the following cytological characteristics of the intracystic fluid: mucus-secreting cells, mucin, and final cytological diagnosis.
15. 14. Proportion of patients in whom AJPD-sec could be performed with a gastroscope with a cap without the need for rescue with a duodenoscope.
16. 15. Evaluate whether any of the variables assessed in objectives 8, 9, 10, 11, 12, or 13 predict the inability to obtain a pancreatic juice sample using a cap-fitted gastroscope after performing both techniques under study.
17. 16. Proportion of patients with adverse effects related to the techniques under study (EUS-FNA and AJPD-secr) defined according to the criteria of the American Society of Gastrointestinal Endoscopy (PB Cotton, et al. Gastrointest Endosc, 2010) at 24 hours and 7 days after the procedures.
18. 17. Evaluate whether any of the variables assessed in objectives 8, 9, 10, 11, 12, or 13 predict the occurrence of adverse effects associated with the techniques under study at 24 hours and 7 days after the procedures.
19. 18. Proportion of patients with Serious Adverse Events at 24 hours and 7 days after the procedures under study.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Sponsor organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Dra. Àngels Ginès

Public contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Dra. Àngels Ginès

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications