HepatoCellular CarcinomaMUTHECNCT03071458
Mutational Landscape in Hepatocellular Carcinoma
An observational study of HepatoCellular Carcinoma and Cirrhosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
The MUTHEC project aims to describe the mutational and transcriptomic landscape of HCC treated by curative treatments (resection, radio frequency ablation, transplantation) as well as advanced HCC together with the analysis of circulating tumor DNA. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HepatoCellular Carcinoma, Cirrhosis
- How many people
- 808 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2008to May 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
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 diagnosed with hepatocellular carcinoma
Who may be able to join
- Written consent of the patient according to the French Law: the French Liver Biobanks network - AFAQ NF S96-900 and Hepatobio bank
- Histologically proven hepatocellular carcinoma
- Available frozen samples
- HCC assessible to a curative treatment (Treated by resection, liver transplantation, radio frequency ablation) or advanced HCC with available biopsy
Who cannot join
- Less than 18 years old
- Pregnancy at the date of the sample
- Parafinn embedded tissue only available
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Translating Molecular Classifications and Genetic Alterations of Hepatocellular Carcinoma in Clinical Care (MUTHEC Project)
The MUTHEC project aims to describe the mutational and transcriptomic landscape of HCC treated by curative treatments (resection, radio frequency ablation, transplantation) as well as advanced HCC together with the analysis of circulating tumor DNA.
Read the detailed description
Scientific context
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. A transcriptomic classification (G1-G6) described by our lab have underlined the heterogeneity of HCC and identified relationship between transcriptomic group and clinical and genetic features. Recently, a diagnostic and molecular algorithm has been developed to perform the diagnosis of benign and malignant hepatocellular tumors and assess the prognosis of resected HCC. Whole-exome sequencing has also identified new oncogenes and tumor suppressor genes in HCC. However, these studies have focused on HCC treated by liver resection and they have to be validated in biopsy and surgical pieces in larges series of patients treated by resection, liver transplantation and radiofrequency ablation (RFA). In addition, next-generation sequencing allows to sequence circulating tumor DNA in plasma of patients with advanced cancer but it has never tested in patients with HCC.
Description of the project The MUTHEC project involves 4 teams in France and aims to perform translation of molecular and genetic classification of HCC in clinical care.
First, the investigators want to draw a genetic landscape of HCC in different clinical settings. The investigators will sequence 30 genes, previously identified by whole exome sequencing, in a series of 120 HCC treated by RFA, 200 HCC treated by liver transplantation and 40 advanced HCC. The investigators also aim to validate our diagnostic and prognostic molecular algorithm (56 genes including the prognostic 5-gene score using quantitative RT-PCR) in different clinical settings and test their uses in formalin-fixed, paraffin-embedded (FFPE) tissues. In addition, the investigators will test surrogate markers of genetic alterations and oncogenic pathways using immunohistochemistry in these series of tumors. All the HCC will be reviewed by expert pathologist in order to perform genotype/phenotype classification. Lastly, the investigators want to conduct a pilot study to sequence circulating tumor DNA. The investigators will use next generation sequencing to detect in the plasma the somatic mutation observed in tumor biopsy. It will allow a non-invasive diagnosis of tumor mutation in the plasma of patients before and after treatment by RFA.
Expected results The investigators aim to extend our knowledge of HCC genetic alterations in the different types of curative treatment (resection, liver transplantation and RFA) and in advanced HCC. In addition, the investigators want to translate this classification using immunohistochemistry to facilitate it uses in routine. These results will be used in the future to identify subgroups predict to response to targeted treatment. In addition, the investigators will validate our diagnostic and prognostic molecular signature in different clinical situation and in FFPE samples. Assessment of prognosis after curative treatment will help to stratify adjuvant treatment in the future and guide therapeutic decision. Finally, sequencing circulating tumor DNA would allow monitoring somatic mutations ("liquid biopsy") after curative treatment and under the selective pressure of targeted therapies.
- Conditions
- HepatoCellular Carcinoma, Cirrhosis
- Medical subject headings
- Carcinoma, Hepatocellular, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with HCC | The cohort is composed of patients with HCC with available tumor and non tumor samples collected retrospectively. These patients have HCC of different stages (localized and advanced stages) It is an observational retrospective study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic and transcriptomic landscape
Identification of the main genetic driver and transcriptomic subgroups among a large panel of HCC
Measured: Up to 3 years
Secondary outcomes (3)
Translation in immunohistochemical markers
The investigators aim to translate the major genetic drivers and oncogenic pathway dysregulated in HCC using immunohistochemistry. The investigators will test surrogate markers of the main genetic alterations and activation of oncogenic pathway using immunohistochemistry in HCC extensively reviewed by expert pathologists.
Measured: Up to 3 years
Detection and sequencing of circulating tumor DNA as a liquid biopsy in HCC
The aim is to conduct a pilot and innovative study to detect mutations in DNA circulating in peripheral blood (ctDNA) in patients with early and advanced HCC. The results will be compared to that obtained in the tumor.
Measured: Up to 3 years
Validation of the molecular classification by integrative analysis
At the end, the investigators aim to perform an integrative analysis of all the data generated by tumor analyses and collected in a database using the various approaches: clinical data, pathological and immunohistochemical features, molecular classification and genetic alterations.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2017
- Study startJan 2008
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HepatoCellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 808 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- jessica zucman-rossi, Md,Phd, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, Francejean-charles Nault, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03071458
- Sponsor's protocol ID
- C 16-71
- Acronym
- MUTHEC
- Status last verified
- Mar 2017
- First submitted
- 2 Jan 2017
- Last updated
- 10 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Blaise L, Ziol M, Campani C, Ganne-Carrie N, Nahon P, Nkontchou G, Zucman-Rossi J, Del Pozo L, Barget N, Boros C, Desjonqueres E, Demory A, Grando V, Pescatori L, Seror O, Sutter O, Nault JC. Utility of tumor and non-tumor biopsies during percutaneous radiofrequency ablation for hepatocellular carcinoma. JHEP Rep. 2025 Apr 22;7(9):101430. doi: 10.1016/j.jhepr.2025.101430. eCollection 2025 Sep.
PubMed 40823168
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translating Molecular Classifications and Genetic Alterations of Hepatocellular Carcinoma in Clinical Care (MUTHEC Project)
- ClinicalTrials.gov ID
- NCT03071458
- Acronym / sponsor ID
- MUTHEC / C 16-71
- Conditions
- HepatoCellular Carcinoma, Cirrhosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 808 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- Jan 2008
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 7 Mar 2017 (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.
The MUTHEC project aims to describe the mutational and transcriptomic landscape of HCC treated by curative treatments (resection, radio frequency ablation, transplantation) as well as advanced HCC together with the analysis of circulating tumor DNA.
Detailed description
Scientific context
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. A transcriptomic classification (G1-G6) described by our lab have underlined the heterogeneity of HCC and identified relationship between transcriptomic group and clinical and genetic features. Recently, a diagnostic and molecular algorithm has been developed to perform the diagnosis of benign and malignant hepatocellular tumors and assess the prognosis of resected HCC. Whole-exome sequencing has also identified new oncogenes and tumor suppressor genes in HCC. However, these studies have focused on HCC treated by liver resection and they have to be validated in biopsy and surgical pieces in larges series of patients treated by resection, liver transplantation and radiofrequency ablation (RFA). In addition, next-generation sequencing allows to sequence circulating tumor DNA in plasma of patients with advanced cancer but it has never tested in patients with HCC.
Description of the project The MUTHEC project involves 4 teams in France and aims to perform translation of molecular and genetic classification of HCC in clinical care.
First, the investigators want to draw a genetic landscape of HCC in different clinical settings. The investigators will sequence 30 genes, previously identified by whole exome sequencing, in a series of 120 HCC treated by RFA, 200 HCC treated by liver transplantation and 40 advanced HCC. The investigators also aim to validate our diagnostic and prognostic molecular algorithm (56 genes including the prognostic 5-gene score using quantitative RT-PCR) in different clinical settings and test their uses in formalin-fixed, paraffin-embedded (FFPE) tissues. In addition, the investigators will test surrogate markers of genetic alterations and oncogenic pathways using immunohistochemistry in these series of tumors. All the HCC will be reviewed by expert pathologist in order to perform genotype/phenotype classification. Lastly, the investigators want to conduct a pilot study to sequence circulating tumor DNA. The investigators will use next generation sequencing to detect in the plasma the somatic mutation observed in tumor biopsy. It will allow a non-invasive diagnosis of tumor mutation in the plasma of patients before and after treatment by RFA.
Expected results The investigators aim to extend our knowledge of HCC genetic alterations in the different types of curative treatment (resection, liver transplantation and RFA) and in advanced HCC. In addition, the investigators want to translate this classification using immunohistochemistry to facilitate it uses in routine. These results will be used in the future to identify subgroups predict to response to targeted treatment. In addition, the investigators will validate our diagnostic and prognostic molecular signature in different clinical situation and in FFPE samples. Assessment of prognosis after curative treatment will help to stratify adjuvant treatment in the future and guide therapeutic decision. Finally, sequencing circulating tumor DNA would allow monitoring somatic mutations ("liquid biopsy") after curative treatment and under the selective pressure of targeted therapies.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with HCC | – | –The cohort is composed of patients with HCC with available tumor and non tumor samples collected retrospectively. These patients have HCC of different stages (localized and advanced stages) It is an observational retrospective study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with hepatocellular carcinoma
Key inclusion criteria (4 listed)
- Written consent of the patient according to the French Law: the French Liver Biobanks network - AFAQ NF S96-900 and Hepatobio bank
- Histologically proven hepatocellular carcinoma
- Available frozen samples
- HCC assessible to a curative treatment (Treated by resection, liver transplantation, radio frequency ablation) or advanced HCC with available biopsy
Key exclusion criteria (3 listed)
- Less than 18 years old
- Pregnancy at the date of the sample
- Parafinn embedded tissue only available
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
Genetic and transcriptomic landscape
Time frame: Up to 3 years
Identification of the main genetic driver and transcriptomic subgroups among a large panel of HCC
3 secondary outcomes
Translation in immunohistochemical markers
Time frame: Up to 3 years
Detection and sequencing of circulating tumor DNA as a liquid biopsy in HCC
Time frame: Up to 3 years
Validation of the molecular classification by integrative analysis
Time frame: Up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Results publication: PubMed 40823168Blaise L, Ziol M, Campani C, Ganne-Carrie N, Nahon P, Nkontchou G, Zucman-Rossi J, Del Pozo L, Barget N, Boros C, Desjonqueres E, Demory A, Grando V, Pescatori L, Seror O, Sutter O, Nault JC. Utility of tumor and non-tumor biopsies during percutaneous radiofrequency ablation for hepatocellular carcinoma. JHEP Rep. 2025 Apr 22;7(9):101430. doi: 10.1016/j.jhepr.2025.101430. eCollection 2025 Sep.
- Individual participant dataSharing planned: No
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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.
jessica zucman-rossi, Md,Phd principal investigator
Institut National de la Santé Et de la Recherche Médicale, France
jean-charles Nault principal investigator
Assistance Publique - Hôpitaux de Paris
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 HepatoCellular Carcinoma and Cirrhosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
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 4 inclusion and 3 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: finished, as of the sponsor's last update on 10 Dec 2025. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Genetic and transcriptomic landscape (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03071458, which also lists 1 linked publication.
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 10 Dec 2025.