Ignite Creation Date:
2024-05-06 @ 6:49 PM
Last Modification Date:
2024-10-26 @ 2:55 PM
Study NCT ID:
NCT05794048
Status:
RECRUITING
Last Update Posted:
2024-02-07
First Post:
2022-10-17
Brief Title:
METabolic PROFILE of Hepatocarcinoma and Pancreatic Tumors
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
METabolic PROFILE of Hepatocarcinoma and Pancreatic Tumors
Status:
RECRUITING
Status Verified Date:
2024-02
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:
PROMETHEP
Brief Summary:
Hepatic hepatocellular carcinoma HCC and pancreatic pancreatic adenocarcinoma ADKP pancreatic neuroendocrine tumors TNEP primary tumors are the most common malignant tumors of the hepato-bilio-pancreatic system and represent a major public health issue At present the management of these tumors is based on recommendations based on the existence of rudimentary prognostic and theranostics markers that do not sufficiently accurately reflect the heterogeneity of tumor biology It therefore seems essential to identify new and more relevant markers in order to optimize the care of these patients in daily practice
Metabolic reprogramming is now recognized as an essential feature of cancer cells allowing them to fuel and maintain their proliferation and tumor growth Such metabolic reprogramming requires modification of several energy pathways the most commonly recognized being the transition from energy metabolism based on oxidative phosphorylation to energy metabolism based on glycolysis even under aerobic conditions Warburg effect In this context the investigators hypothesized that the consumption of nutrients by the tumor cell differs significantly from that of the normal cell in order to support its increased energy needs and that this important and specific metabolic reprogramming would be correlated with the histo-prognostic and theranostics factors of these tumors Preliminary analyses on surgical resection parts conducted by the various partners in 2019 made it possible to characterize the metabolic signatures of a series of HCC and ADKP resected using the Metafora biosystems technology platform These signatures reflect a metabolic program characteristic of these tumors which reveal strong specificities Similarly a candidate signature correlating with the presence of vascular microscopic invasion has been identified in HCC and the level of activation of glycolysis and glutaminolysis by certain ADKP cells also appears as a trait of interest vis-à-vis the aggressiveness of this cancer
Thus the current project will aim to confirm the feasibility of identifying specific prognostic and theranostics metabolic signatures early on biopsy samples and or circulating blood cells
Metabolic reprogramming is now recognized as an essential feature of cancer cells allowing them to fuel and maintain their proliferation and tumor growth Such metabolic reprogramming requires modification of several energy pathways the most commonly recognized being the transition from energy metabolism based on oxidative phosphorylation to energy metabolism based on glycolysis even under aerobic conditions Warburg effect In this context the investigators hypothesized that the consumption of nutrients by the tumor cell differs significantly from that of the normal cell in order to support its increased energy needs and that this important and specific metabolic reprogramming would be correlated with the histo-prognostic and theranostics factors of these tumors Preliminary analyses on surgical resection parts conducted by the various partners in 2019 made it possible to characterize the metabolic signatures of a series of HCC and ADKP resected using the Metafora biosystems technology platform These signatures reflect a metabolic program characteristic of these tumors which reveal strong specificities Similarly a candidate signature correlating with the presence of vascular microscopic invasion has been identified in HCC and the level of activation of glycolysis and glutaminolysis by certain ADKP cells also appears as a trait of interest vis-à-vis the aggressiveness of this cancer
Thus the current project will aim to confirm the feasibility of identifying specific prognostic and theranostics metabolic signatures early on biopsy samples and or circulating blood cells
Detailed Description:
Primary liver tumours hepatocellular carcinoma HCC and pancreatic tumours pancreatic adenocarcinoma ADKP pancreatic neuroendocrine tumours NETs are the most frequent malignant tumours of the hepatobiliopancreatic system and represent a major public health issue One of the main lines of research for these tumors consists in the early identification of prognostic and theranostic factors to adapt the management of patients as closely as possible to the specificities of their pathology This identification is currently sorely lacking in daily clinical practice Thus unlike what is done for other types of neoplastic pathologies such as breast cancer the management of primary liver and pancreatic tumors is still often based on recommendations based on the existence of rudimentary prognostic and theranostic markers that do not reflect sufficiently faithfully the heterogeneity of tumor biology It is therefore essential to identify new more relevant markers in order to optimize the management of these patients in daily practice
Metabolic reprogramming is now recognized as an essential characteristic of cancer cells allowing them to fuel and maintain their proliferation and tumor growth Such metabolic reprogramming requires modification of several energy pathways the most commonly recognized being the shift from energy metabolism based on oxidative phosphorylation to energy metabolism based on glycolysis even under aerobic conditions Warburg effect Other metabolic pathways such as increased glutaminolysis have recently been identified In this context we hypothesized that the consumption of nutrients by the tumor cell differs significantly from that of the normal cell in order to support its increased energy needs and that this important and specific metabolic reprogramming would be correlated with the histo-prognostic and theranostic factors of these tumors Within ADKPs 2 molecular subtypes have been described a very aggressive basal-like subtype with increased glycolytic metabolism and metastatic properties and a classical subtype better differentiated with better prognosis The identification of these subtypes is currently only possible by RNA-seq a technology not practiced routinely Similarly metabolism appears to define a subgroup of aggressive NETs Indeed NETs with high glucose uptake visible on 18FDG PET-CT scan have a worse prognosis This type of examination also showed that there was spatial metabolic heterogeneity primary tumor vs metastasis and temporal metabolic heterogeneity in these tumors and that the latter was correlated with prognosis
Preliminary analyses conducted by the various partners in 2019 made it possible to characterize the metabolic signatures of a series of resected HCC and ADKP using Metafora biosystems technological platform
These signatures reflect a metabolic program characteristic of these tumors which reveal strong specificities Similarly a candidate signature correlating with the presence of microscopic vascular invasion has been identified in HCC and the level of activation of glycolysis and glutaminolysis by some ADKP cells also appears as a trait of interest vis-à-vis the aggressiveness of this cancer
As these results were obtained on surgical resection parts the current project will therefore aim to confirm the feasibility of identifying specific prognostic and theranostic metabolic signatures early on biopsy sampling or circulating blood cells
This multicenter study includes 300 patients 100 patients for each tumor type and aims to identify a prognostic metabolic signature from tumor tissue samples of HCC ADKP and pancreatic NETs
Metabolic reprogramming is now recognized as an essential characteristic of cancer cells allowing them to fuel and maintain their proliferation and tumor growth Such metabolic reprogramming requires modification of several energy pathways the most commonly recognized being the shift from energy metabolism based on oxidative phosphorylation to energy metabolism based on glycolysis even under aerobic conditions Warburg effect Other metabolic pathways such as increased glutaminolysis have recently been identified In this context we hypothesized that the consumption of nutrients by the tumor cell differs significantly from that of the normal cell in order to support its increased energy needs and that this important and specific metabolic reprogramming would be correlated with the histo-prognostic and theranostic factors of these tumors Within ADKPs 2 molecular subtypes have been described a very aggressive basal-like subtype with increased glycolytic metabolism and metastatic properties and a classical subtype better differentiated with better prognosis The identification of these subtypes is currently only possible by RNA-seq a technology not practiced routinely Similarly metabolism appears to define a subgroup of aggressive NETs Indeed NETs with high glucose uptake visible on 18FDG PET-CT scan have a worse prognosis This type of examination also showed that there was spatial metabolic heterogeneity primary tumor vs metastasis and temporal metabolic heterogeneity in these tumors and that the latter was correlated with prognosis
Preliminary analyses conducted by the various partners in 2019 made it possible to characterize the metabolic signatures of a series of resected HCC and ADKP using Metafora biosystems technological platform
These signatures reflect a metabolic program characteristic of these tumors which reveal strong specificities Similarly a candidate signature correlating with the presence of microscopic vascular invasion has been identified in HCC and the level of activation of glycolysis and glutaminolysis by some ADKP cells also appears as a trait of interest vis-à-vis the aggressiveness of this cancer
As these results were obtained on surgical resection parts the current project will therefore aim to confirm the feasibility of identifying specific prognostic and theranostic metabolic signatures early on biopsy sampling or circulating blood cells
This multicenter study includes 300 patients 100 patients for each tumor type and aims to identify a prognostic metabolic signature from tumor tissue samples of HCC ADKP and pancreatic NETs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None