Clinical trial NCT06549725: Clinical Performance of Medical Device Software "Lipidica 1.0" for Processing Data Generated by Lipidomic Analysis in Pancreatic Cancer Screening
Official title: Clinical Performance of Medical Device Software "Lipidica 1.0" for Processing Data Generated by Lipidomic Analysis in Pancreatic Cancer Screening
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pancreas Cancer
Pancreatic Ductal Adenocarcinoma
Hereditary Diseases
Pancreatitis, Chronic
Lead sponsor: Lipidica, a.s.
Sponsor class: INDUSTRY
First posted: 2024-08-12
Enrollment: 419
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: Histologically confirmed diagnosis of resectable Pancreatic cancer Arm 2: Participants without PaC but at higher risk of Pancreatic cancer disease due to their predispositions
Primary purpose: SCREENING

Brief summary: Software "Lipidica" is intended to be used for processing data generated by the in-house in vitro diagnostic medical device for lipidomic testing for the purpose of screening Pancreatic cancer (PaC) in the population at high risk of this cancer due to familial risk, selected gene mutations or hereditary pancreatic diseases.

The primary objective is to verify that the investigational MDSW can discriminate between results of patients with Pancreatic cancer and persons without Pancreatic cancer but at higher risk of this cancer disease due to their predispositions.

Participants will:

* come to baseline and end of study visit for blood sampling and medical imaging
* some participant will undertake one more visit depending on their results on baseline

Detailed description: Pancreatic cancer (PaC) is one of the cancer diseases with the worst prognosis, as mortality almost equals the incidence. In the Czech Republic, the incidence of pancreatic ductal adenocarcinoma (PDAC) has had a clear upward trend since the late 1970s, and in 2018, 21.9 new cases per 100,000 persons were reported.

PDAC is associated with a poor prognosis for several reasons. Due to the usual asymptomatic course or occurrence of only non-specific symptoms, it is usually detected in an advanced stage. Moreover, the diagnosis by standard methods can be difficult in the early stages, and investigators lack sensitive and specific tumor markers. The disease forms distant metastases rapidly, which creates a very short time interval for effective curative interventions. So far, PaC screening possibilities in the Czech Republic are limited to several academic research screening cohorts.

Five-year survival, regardless of clinical stage, is 7-9%. The resectable disease is detected in 10% of patients with a 5-year survival of 42%. Locally advanced unresectable disease is found in about 30% of patients with a 5-year survival of 12%, and metastatic disease is diagnosed in about 60% of patients with a 5-year survival of only approx. 3%.

PaC screening is not suitable for an unselected population. By contrast, it is vital for individuals with a high risk of developing this disease due to family history and/or genetic predispositions. Early diagnosis resulted in more curative resections and longer survival in this population thanks to the screening programs. First economic evaluations described the possible cost-effectiveness of screening high-risk individuals.

Changes in plasma lipid concentrations were reported in various cancer types (bladder, breast, colorectal, gastric, liver, kidney, lung, oesophageal, ovarian, prostate, thyroid, and pancreas). The altered plasma lipid profile may originate not only from tumor cells, tumor stroma, and apoptotic cells but also from an immune response.

Previous study robustly proved a specific lipidomic phenotype in patients with PDAC across stages, age, treatments, or the presence of diabetes. Multiple lipid species were significantly downregulated in the plasma of PDAC patients, such as very long-chain monounsaturated sphingomyelins, ceramides and (lyso)phosphatidylcholines. The study showed that lipid profiling can discriminate between patients with PDAC and healthy controls or patients with pancreatitis. This clinical performance study (CPS) follows on from the previous study by Wolrab et al.

Eligibility criteria: Inclusion Criteria Arm1:

* Age ≥ 18 years
* Signed informed consent
* Histologically confirmed diagnosis of resectable PaC

Exclusion Criteria Arm 1:

* History of any other cancer disease
* Present incurable malignancy
* Unfit for radical curative resection of the tumor
* Vegan or vegetarian diet

Inclusion Criteria Arm2:

* Age ≥ 18 years
* Signed informed consent
* High risk of PaC due to the presence of one of the following risk factors:

  1. Family history of PaC (≥ 2 first-degree or second-degree relatives with PaC in the same family line)
  2. Confirmed germline mutation of STK11 (LKB1) regardless of family history
  3. Confirmed germline mutation of CDKN2A leading to the alteration of p16 regardless of family history
  4. Confirmed germline mutation of APC, ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, PALB2 or TP53 AND ≥ 1 first-degree or second-degree relative with PaC
  5. Present hereditary pancreatitis (recurrent acute pancreatitis or chronic pancreatitis and confirmed germline mutation of PRSS1)
* Age:

  1. Person with a family history of PaC: \> 50 years or 10 years before the diagnosis of PaC in the youngest family member (whichever comes first)
  2. Person with STK11 mutation: \> 35 years or 10 years before the diagnosis of PaC in the youngest family member (whichever comes first)
  3. Person with CDKN2A mutation: \> 40 years or 10 years before the diagnosis of PaC in the youngest family member (whichever comes first)
  4. Person with APC, ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, PALB2 or TP53 mutation: \> 45 years or 10 years before the diagnosis of PaC in the youngest family member (whichever comes first)
  5. Person with hereditary pancreatitis: \> 40 years or 20 years after the 1st attack (whichever comes first)

Exclusion Criteria Arm 2:

* Pregnancy of planning to conceive in the next 12 months
* History of any cancer disease
* Present incurable malignancy
* Inability to undergo planned medical imaging or blood sampling
* Vegan or vegetarian diet

Primary outcomes:
measure: The primary objective is to verify that the investigational MDSW can discriminate between results of patients with PaC and persons without PaC but at higher risk of this cancer disease due to their predispositions.
timeFrame: Interim analysis 1 year from first subject enrolled and through study completion (an average of 3 years)
Secondary outcomes:
Other outcomes:
measure: Glycosylated haemoglobin (HbA1c) levels with PaC diagnosis status
timeFrame: Through study completion (an average of 3 years)
measure: Effect of CA 19-9 and CEA tumor markers on sensitivity and specificity
timeFrame: Through study completion (an average of 3 years)
measure: Several predefined cut-off values
timeFrame: Through study completion (an average of 3 years)
measure: The effect of the normalization step on the calculation of lipid concentrations and its impact on the clinical performance of MDSW.
timeFrame: Through study completion (an average of 3 years)
measure: Verification of the clinical performance of next version(s) of MDSW "Lipidica"
timeFrame: Through study completion (an average of 3 years)
Locations:
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
city: Praha
country: Czechia
facility: Fakultni nemocnice Bulovka
city: Praha
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha
country: Czechia
facility: Fakultni Thomayerova nemocnice
city: Praha
country: Czechia
facility: Institut klinicke a experimentalni mediciny
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice
city: Ústí Nad Labem
country: Czechia
facility: Masarykova nemocnice v Usti nad Labem
city: České Budějovice
country: Czechia
facility: Nemocnice Ceske Budejovice
Study officials:
affiliation: Lipidica, a.s.
name: Karolina Kasparova
role: STUDY_DIRECTOR
References: