Ignite Creation Date:
2025-12-24 @ 11:58 PM
Ignite Modification Date:
2026-01-05 @ 6:00 PM
Study NCT ID:
NCT03071458
Status:
COMPLETED
Last Update Posted:
2025-12-10
First Post:
2017-01-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Mutational Landscape in Hepatocellular Carcinoma
Sponsor:
Institut National de la Santé Et de la Recherche Médicale, France
Organization:
Study Overview
Official Title:
Translating Molecular Classifications and Genetic Alterations of Hepatocellular Carcinoma in Clinical Care (MUTHEC Project)
Status:
COMPLETED
Status Verified Date:
2017-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MUTHEC
Brief 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.
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.
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: