Comparison of Secretin-Stimulated Duodenopancreatic Juice Aspiration Versus EUS-Guided FNA for Molecular Analysis in Intraductal Papillary Mucinous Neoplasia

Trial ID: 2024-519972-21-00
Protocol: RESCUE
Sponsor: Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

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Diseases & Conditions

Intraductal papillary mucinous neoplasm

Objectives

The primary objective of this study is to compare the **detection rate** of somatic mutations in **GNAS** and **KRAS** in liquid samples obtained by two techniques: Endoscopic Aspiration of Duodenopancreatic Juice after Secretin Stimulation (ADPJ-secr) and Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) in patients with Intraductal Papillary Mucinous Neoplasia (IPMN). This is clinically relevant as it may enhance the diagnostic accuracy for pancreatic cancer, potentially leading to improved patient outcomes through earlier and more precise intervention.

Secondary objectives include:

Comparing the detection rate of somatic mutations in **Tp53** in samples from patients with IPMN who underwent pancreatic resection within 12 months.
Comparing the concentration and quality of **DNA** obtained by both techniques.
Comparing the sensitivity and specificity of the two techniques for diagnosing IPMN in the specified patient subgroup.
Comparing the positive and negative predictive values of malignancy of **Tp53** mutations between the two techniques.
Correlating the mutational profile with clinical-epidemiological data, morphological characteristics, technical characteristics, and various data of the intracystic fluid.
Evaluating the feasibility of ADPJ-sec using a gastroscope with a cap and the incidence of adverse effects related to both techniques, including serious adverse events at 24 hours and 7 days post-procedure.

These secondary objectives aim to provide a comprehensive evaluation of the diagnostic capabilities and safety profiles of the techniques under study, potentially informing clinical practice in the management of pancreatic neoplasms.

Participants

The clinical trial involves participants diagnosed with **pancreatic cancer** or intraductal papillary mucinous neoplasia (IPMN). The study population includes both male and female subjects over the age of 18, with no specific upper age limit mentioned. Participants are required to be in general good health, aside from their diagnosed condition, and must be willing to comply with study procedures and provide informed consent. The trial population was selected based on specific diagnostic criteria related to IPMN, including imaging characteristics and intracystic fluid analysis. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, indicating that additional ethical considerations are in place to protect these individuals. Key inclusion criteria involve the willingness of women of childbearing potential to use effective contraceptive methods or practice sexual abstinence during the study period.

Plans and Procedures

The clinical trial is designed to evaluate the **diagnostic yield** of endoscopic aspiration of duodenopancreatic juice after **secretin** stimulation compared to endoscopic ultrasound-guided fine needle aspiration for molecular analysis of intraductal papillary mucinous neoplasia (IPMN). This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to run from September 13, 2023, to December 31, 2026, with participant involvement lasting up to 12 months from the time of inclusion.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, willingness to comply with study procedures, and specific diagnostic criteria for IPMN. Following the screening, eligible participants will be randomized to one of the two diagnostic techniques under investigation. Subsequent follow-up visits will be scheduled to monitor the participants' health status, collect samples, and assess the presence of somatic mutations in GNAS and KRAS genes. The end-of-study visit will occur 12 months after the initial procedure, where final assessments and sample collections will be conducted.

The expected length of participant involvement is approximately 12 months, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The primary endpoint is the proportion of patients with IPMN exhibiting GNAS and KRAS mutations in samples obtained by the two techniques. Secondary endpoints include the evaluation of additional mutations, DNA concentration, and the suitability of samples for molecular analysis. The study aims to provide valuable insights into the effectiveness of these diagnostic techniques in detecting genetic mutations associated with IPMN.

Treatment

The clinical trial involves the administration of the experimental medication **Chirhostim**, which contains the active substance **secretin synthetic human**. This medication is provided in the pharmaceutical form of a **lyophilisate for solution for injection**. The administration route is via **intravenous infusion**. The dosage is calculated based on body weight, with a maximum daily dose of 0.2 µg/kg. The total dose administered over the treatment period is also capped at 0.2 µg/kg. The treatment period is limited to a single day. The medication is not formulated specifically for pediatric use and is not classified as an orphan drug.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies or comparator treatments as deemed necessary by the study protocol. These non-experimental treatments are not specified in the provided data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial aims to compare the detection rate of somatic mutations in GNAS and KRAS in liquid samples obtained by the techniques under study in patients with intraductal papillary mucinous neoplasia.

Efficacy

Efficacy in this clinical trial will be assessed by comparing the detection rate of somatic mutations in **GNAS** and **KRAS** in liquid samples obtained through two different techniques: Endoscopic aspiration of duodenopancreatic juice after secretin stimulation (ADPJ-secr) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The primary endpoint is the proportion of patients with intraductal papillary mucinous neoplasia (IPMN) exhibiting these mutations in intracystic fluid obtained by EUS-FNA versus pancreatic juice obtained by ADPJ-secr.

Secondary endpoints include the proportion of patients with **Tp53** mutations in samples obtained by both techniques, DNA concentration in samples, and the suitability of samples for molecular analysis. Suitability is determined using a Qubit fluorometer, which detects full double-stranded DNA. Additional secondary endpoints involve evaluating the association between mutational status and various clinical, morphological, and biochemical variables, as well as technical characteristics of the procedures. The trial will also assess the proportion of patients experiencing adverse effects related to the techniques, as defined by the American Society of Gastrointestinal Endoscopy, at 24 hours and 7 days post-procedure.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Be a man or woman over 18 years of age.
Willing to comply with the study procedures described in the protocol.
Willing and able to give written informed consent.
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.
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.
4.3. IPMN with indication for surgical resection of the lesion.
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.
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.

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Exclusion Criteria

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.
Acute pancreatitis within the 30 days prior to inclusion.
Pregnant women, women with the possibility of pregnancy during the month prior to inclusion, or women who are breastfeeding.
Coagulopathy (PT < 25%, INR > 1.5, platelets < 50,000/mL) preventing FNA.
Renal failure with GFR < 30 mL/min or patients on dialysis.
Known hypersensitivity to any component of the ChiRhoStim® (human secretin) formulation.
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).