Hepatobiliary CancersNCT06777914
Familial Intrahepatic Cholestasis-related Genes Associated with Disease Susceptibility in Hepato-biliary Cancers
An observational study of Hepatobiliary Cancers and Progressive Familial Intrahepatic Cholestasis (PFIC), run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 5 sites in Italy.
Trial summary
This is a cross-sectional, multicenter tissue study with an exploratory aim to estimate the prevalence of genetic mutations that predispose individuals to diseases in the context of cholestatic disorders and hepatobiliary neoplasms. It is intended as a hypothesis-generating study for future empirical investigations. Read more about this study
- Who is it for?
- Ages 12 months and older
- Conditions the study is for
- Hepatobiliary Cancers, Progressive Familial Intrahepatic Cholestasis (PFIC), Cholestatic Liver Disease
- How many people
- 600 participants
- Where
- 5 sitesItaly
- Study dates
- 22 Oct 2024to Oct 2027
- 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 12 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Subjects with a diagnosis of HBCs who have undergone liver resection or liver transplantation, and a population of patients affected by CCLDs.
Who may be able to join
- Instrumental or histological diagnosis of HBCs, defined as primary liver and/or biliary tumors (hepatocellular carcinoma, cholangiocarcinoma, hepatocholangiocarcinoma) occurring in patients without apparent underlying chronic liver disease or in the context of cryptogenic chronic liver disease;
- Curative treatment through surgical resection of the neoplasm or liver transplantation
- Diagnosis of CCLDs defined as:
- GGT and/or alkaline phosphatase >1.5 times the normal values in two or more measurements taken at least 6 months apart,
- A history of pruritus combined with [BA] >10 mmol/l for a period of ≥6 months.
- Obtaining written informed consent
Who cannot join
- Other documented causes of chronic liver disease that can justify the clinical phenotype include:
- Primary biliary cholangitis Primary sclerosing cholangitis IgG4-related cholangiopathy Obstructive jaundice excluded by the demonstration of normal bile duct anatomy Negative virological tests for HBV, HCV, HEV Alcohol abuse Hemochromatosis Wilson's disease Alpha-1 antitrypsin deficiency
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Italy5 sites, 5 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Programma Chirurgia addominale nell'insufficienza d'organo terminale e nei pazienti con trapianto d'organo
Bologna, Bologna, 40138
Matteo Ravaioli, 051.214.4810, matteo.ravaioli6@unibo.it
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - UO Chirurgia Epatobiliare e dei Trapianti
Bologna, Bologna, 40138
Chiara Zanfi, 051.214.4750, chiara.zanfi@aosp.bo.it
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - UO Gastroenterologia
Bologna, Bologna, 40138
Francesco Azzaroli, 051.214.3888, francesco.azzaroli@unibo.it
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - UO Medicina Interna per il trattamento delle gravi insufficienze d'organo
Bologna, Bologna, 40138
Giovanni Vitale, 0512143702, giovanni.vitale@aosp.bo.it
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - UO Medicina Interna, malattie epatobiliari e immunoallergologiche
Bologna, Bologna, 40138
Fabio Piscaglia, 051.214.2568, fabio.piscaglia@unibo.it
About this study
This is a cross-sectional, multicenter tissue study with an exploratory aim to estimate the prevalence of genetic mutations that predispose individuals to diseases in the context of cholestatic disorders and hepatobiliary neoplasms. It is intended as a hypothesis-generating study for future empirical investigations.
Read the detailed description
This is a multicenter, cross-sectional tissue study designed to explore the prevalence of genetic mutations associated with cholestatic liver diseases and hepatobiliary neoplasms. It aims to generate hypotheses for future empirical research.
Patient data will be collected, including medical history, imaging tests (e.g., abdominal ultrasound, CT, and MRI), and liver function tests, along with [BA] levels. Non-invasive liver fibrosis assessment (FibroScan or Shear-Wave elastography) and, where applicable, liver biopsies will be included, all referenced to the time of genetic testing.
Molecular genetic analysis of PFIC will be conducted using a multiplex PCR NGS panel covering 37 genes. If clinical suspicion remains high despite negative NGS results, Whole Exome Sequencing (WES) will be used to identify previously unknown PFIC-related genes. WES will prioritize patients with hepatobiliary cancers on a healthy liver or without advanced fibrosis and those with a family history of PFIC or related conditions.
Variants will be filtered based on clinical significance, gene-disease associations, and functional predictions, using resources like ClinVar, HGMD, and Personal Genomics PGVD. WES analysis will include at least one affected parent when available, with de novo mutations considered when both parents are involved.
Only pathogenic or potentially pathogenic variants will be reported, confirmed by Sanger sequencing. Genetic counseling will be offered for patients with significant findings. Tumor tissue samples will also be analyzed for somatic mutations, potentially guiding therapeutic decisions or family screening.
NGS for somatic mutations will use tumor samples collected for clinical purposes, with findings compared to germline mutations. This may inform treatment options and surveillance protocols for relatives. The data will be stored in an electronic archive using REDCap and analyzed by clinical staff. The collected data will include clinical history, liver function tests, response to ursodeoxycholic acid, liver fibrosis stage, and molecular results, along with relevant family histories and therapies.
For patients undergoing surgery, the data will also cover pre-operative assessments, surgical techniques, and post-operative outcomes.
- Conditions
- Hepatobiliary Cancers, Progressive Familial Intrahepatic Cholestasis (PFIC), Cholestatic Liver Disease
- Medical subject headings
- Cholestasis, progressive familial intrahepatic 1
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of Pathogenic and Variant Mutations in PFIC Genes in HBCs and CCLDs Patients
To estimate the prevalence of pathogenic germline mutations, probably pathogenic mutations, variants of uncertain significance, probably benign variants, and benign variants in the genes responsible for PFIC in individuals diagnosed with HBCs who have undergone liver resection or liver transplantation, and in a population of patients with CCLDs.
Measured: 3 years
Secondary outcomes (4)
Identifying New PFIC-Associated Genes in HBCs and CCLDs Patients Negative for NGS Analysis via WES
Estimate the percentage of patients carrying newly identified genes potentially responsible for PFIC, discovered through WES
Measured: 3 years
Identification of Somatic Mutations in Tumor Tissue Samples from Patients Undergoing Liver Resection or Transplantation for HBCs
Estimate percentage of patients carrying somatic mutations identified through NGS (in PFIC-related genes) or through WES.
Measured: 3 years
Laboratory and Clinical Features of HBCs and CCLDs Patients
Estimate percentage of patients with PFIC gene mutations and BRIC, LPAC, ICP, DIC phenotype, advanced fibrosis, pruritus, and/or neonatal jaundice
Measured: 3 years
Comparison of Allelic Frequency of PFIC-Related Mutations in the NGS Panel between the Study Population and gnomAD Database
Estimate the proportion of a specific allele among the total alleles identified in the NGS genetic analysis.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2025
- Study start22 Oct 2024
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatobiliary CancersStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- 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
- Other
- Time perspective
- Other
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giovanni Vitale, MD, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06777914
- Sponsor's protocol ID
- HBCs-PFIC
- Other IDs
- RC-2024-2790618
- Status last verified
- Nov 2024
- First submitted
- 3 Dec 2024
- Last updated
- 16 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Familial Intrahepatic Cholestasis-related Genes Associated with Disease Susceptibility in Hepato-biliary Cancers
- ClinicalTrials.gov ID
- NCT06777914
- Acronym / sponsor ID
- HBCs-PFIC
- Conditions
- Hepatobiliary Cancers, Progressive Familial Intrahepatic Cholestasis (PFIC), Cholestatic Liver Disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 22 Oct 2024 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 16 Jan 2025 (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.
This is a cross-sectional, multicenter tissue study with an exploratory aim to estimate the prevalence of genetic mutations that predispose individuals to diseases in the context of cholestatic disorders and hepatobiliary neoplasms. It is intended as a hypothesis-generating study for future empirical investigations.
Detailed description
This is a multicenter, cross-sectional tissue study designed to explore the prevalence of genetic mutations associated with cholestatic liver diseases and hepatobiliary neoplasms. It aims to generate hypotheses for future empirical research.
Patient data will be collected, including medical history, imaging tests (e.g., abdominal ultrasound, CT, and MRI), and liver function tests, along with [BA] levels. Non-invasive liver fibrosis assessment (FibroScan or Shear-Wave elastography) and, where applicable, liver biopsies will be included, all referenced to the time of genetic testing.
Molecular genetic analysis of PFIC will be conducted using a multiplex PCR NGS panel covering 37 genes. If clinical suspicion remains high despite negative NGS results, Whole Exome Sequencing (WES) will be used to identify previously unknown PFIC-related genes. WES will prioritize patients with hepatobiliary cancers on a healthy liver or without advanced fibrosis and those with a family history of PFIC or related conditions.
Variants will be filtered based on clinical significance, gene-disease associations, and functional predictions, using resources like ClinVar, HGMD, and Personal Genomics PGVD. WES analysis will include at least one affected parent when available, with de novo mutations considered when both parents are involved.
Only pathogenic or potentially pathogenic variants will be reported, confirmed by Sanger sequencing. Genetic counseling will be offered for patients with significant findings. Tumor tissue samples will also be analyzed for somatic mutations, potentially guiding therapeutic decisions or family screening.
NGS for somatic mutations will use tumor samples collected for clinical purposes, with findings compared to germline mutations. This may inform treatment options and surveillance protocols for relatives. The data will be stored in an electronic archive using REDCap and analyzed by clinical staff. The collected data will include clinical history, liver function tests, response to ursodeoxycholic acid, liver fibrosis stage, and molecular results, along with relevant family histories and therapies.
For patients undergoing surgery, the data will also cover pre-operative assessments, surgical techniques, and post-operative outcomes.
Study design
- Observational model
- Other
- Time perspective
- Other
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects with a diagnosis of HBCs who have undergone liver resection or liver transplantation, and a population of patients affected by CCLDs.
Key inclusion criteria (6 listed)
- Instrumental or histological diagnosis of HBCs, defined as primary liver and/or biliary tumors (hepatocellular carcinoma, cholangiocarcinoma, hepatocholangiocarcinoma) occurring in patients without apparent underlying chronic liver disease or in the context of cryptogenic chronic liver disease;
- Curative treatment through surgical resection of the neoplasm or liver transplantation
- Diagnosis of CCLDs defined as:
- Obtaining written informed consent
Key exclusion criteria (2 listed)
- Other documented causes of chronic liver disease that can justify the clinical phenotype include:
- Primary biliary cholangitis Primary sclerosing cholangitis IgG4-related cholangiopathy Obstructive jaundice excluded by the demonstration of normal bile duct anatomy Negative virological tests for HBV, HCV, HEV Alcohol abuse Hemochromatosis Wilson's disease Alpha-1 antitrypsin deficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of Pathogenic and Variant Mutations in PFIC Genes in HBCs and CCLDs Patients
Time frame: 3 years
To estimate the prevalence of pathogenic germline mutations, probably pathogenic mutations, variants of uncertain significance, probably benign variants, and benign variants in the genes responsible for PFIC in individuals diagnosed with HBCs who have undergone liver resection or liver transplantation, and in a population of patients with CCLDs.
4 secondary outcomes
Identifying New PFIC-Associated Genes in HBCs and CCLDs Patients Negative for NGS Analysis via WES
Time frame: 3 years
Identification of Somatic Mutations in Tumor Tissue Samples from Patients Undergoing Liver Resection or Transplantation for HBCs
Time frame: 3 years
Laboratory and Clinical Features of HBCs and CCLDs Patients
Time frame: 3 years
Comparison of Allelic Frequency of PFIC-Related Mutations in the NGS Panel between the Study Population and gnomAD Database
Time frame: 3 years
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 16 Jan 2025.
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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.
Giovanni Vitale, MD principal investigator
IRCCS Azienda Ospedaliero-Universitaria di Bologna
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatobiliary Cancers and Progressive Familial Intrahepatic Cholestasis (PFIC), run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 5 sites 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 6 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
Contact Giovanni Vitale (051.214.3702, giovanni.vitale@aosp.bo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of Pathogenic and Variant Mutations in PFIC Genes in HBCs and CCLDs Patients (time frame: 3 years). 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 16 Jan 2025.