Ignite Creation Date:
2024-05-06 @ 6:43 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05754788
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2023-05-26
First Post:
2023-01-10
Brief Title:
Gene Expression Profile of Resected Pancreatic and Ampullary Adenocarcinoma at Favorable Prognosis
Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Organization:
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Study Overview
Official Title:
Identification of Gene Expression Profile Associated With Favorable Prognosis in Patients Undergoing Radical Surgery for Pancreatic and Ampullary Adenocarcinoma
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2023-05
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:
None
Brief Summary:
The study aims at evaluating spatially resolved gene expression profiles of pancreatic and ampullary adenocarcinoma at favorable prognosis after surgical resection in order to identify molecular features associated to a less aggressive biologic behavior that may benefit from upfront surgery
Detailed Description:
Despite technical improvements surgery for pancreatic adenocarcinoma is still burdened by poor survival outcomes of only 10 at 5 years due to very high locoregional and distant recurrence rates In order to improve such disappointing results several studies are now focusing on the role of neoadjuvant treatment Recent evidence shows that neoadjuvant treatment may achieve improved intention-to-treat survival outcome increased rates of margin-negative resections and decreased incidence of lymph node metastases However all surgical series report that a limited subset of patients achieve long-term survival following radical surgical resection
After a systematic review of the available evidence on molecular profiling of pancreatic adenocarcinoma published until today the investigators have undertaken a retrospective study aimed at investigating the presence of possible genetic factors associated to a less aggressive clinical behavior Clinical biological and pathological features collected in a prospectively maintained database of radical surgery for pancreatic adenocarcinoma will be retrospectively reviewed together with an analysis of molecular features on surgical samples belonging to patients radically operated at the National Institute of Cancer of Milan Such features may be used to identify those patients who may benefit from upfront surgery in such group vascular resections and reconstructions could be considered more liberally
The study will consist of 2 phases
1 A preliminary exploratory phase group A based on approximately 20 surgical samples of patients with surgically resected pancreatic adenocarcinoma not treated by neoadjuvant chemotherapy in order to evaluate the intrinsic role of tumor biology and avoid the selection of molecular features associated to treatment response This cohort will consist of 2 groups of 10 patients each with prognostically favorable RFS60 months and unfavorable tumors RFS12 months respectively Patients from the 2 groups will be matched for clinicopathological tumor-related features Spatially resolved transcriptomic analysis will be performed by the GeoMx Digital Spatial Profiler DSP NanoString Technologies Seattle WA USA on samples of the two groups and the resulting gene expression profiles will be compared in order to identify different patterns of gene expression in prognostically different pancreatic adenocarcinomas Such patterns will also be compared with the TCGA database
2 A subsequent expanded phase based on the results of the previous exploration will take place in case a different gene expression profile is identified The internal validation set group B consists in additional 20 surgical samples associated to favorable and unfavorable prognosis 10 patients each respectively belonging to the same institutional series and matched for clinicopathological tumor-related features RNA-seq analysis will be carried out on these surgical samples aiming at confirming the results of the exploratory analysis and refine the gene expression profile In this subset the enrolment of patients who underwent neoadjuvant treatment will be allowed
Due to the limited number samples from patients affected by ampullary adenocarcinoma with favorable prognosis will be analyzed in one step and compared to matched cases with unfavorable prognosis 8 patients each group C
Following the identification of gene expression profiles both for pancreatic and ampullary adenocarcinoma an external validation set will be enrolled in order to perform RNA-seq analysis on additional 60-80 surgical samples from other institutions and validate the prognostic relevance of the identified pattern in predicting a less aggressive disease course
After a systematic review of the available evidence on molecular profiling of pancreatic adenocarcinoma published until today the investigators have undertaken a retrospective study aimed at investigating the presence of possible genetic factors associated to a less aggressive clinical behavior Clinical biological and pathological features collected in a prospectively maintained database of radical surgery for pancreatic adenocarcinoma will be retrospectively reviewed together with an analysis of molecular features on surgical samples belonging to patients radically operated at the National Institute of Cancer of Milan Such features may be used to identify those patients who may benefit from upfront surgery in such group vascular resections and reconstructions could be considered more liberally
The study will consist of 2 phases
1 A preliminary exploratory phase group A based on approximately 20 surgical samples of patients with surgically resected pancreatic adenocarcinoma not treated by neoadjuvant chemotherapy in order to evaluate the intrinsic role of tumor biology and avoid the selection of molecular features associated to treatment response This cohort will consist of 2 groups of 10 patients each with prognostically favorable RFS60 months and unfavorable tumors RFS12 months respectively Patients from the 2 groups will be matched for clinicopathological tumor-related features Spatially resolved transcriptomic analysis will be performed by the GeoMx Digital Spatial Profiler DSP NanoString Technologies Seattle WA USA on samples of the two groups and the resulting gene expression profiles will be compared in order to identify different patterns of gene expression in prognostically different pancreatic adenocarcinomas Such patterns will also be compared with the TCGA database
2 A subsequent expanded phase based on the results of the previous exploration will take place in case a different gene expression profile is identified The internal validation set group B consists in additional 20 surgical samples associated to favorable and unfavorable prognosis 10 patients each respectively belonging to the same institutional series and matched for clinicopathological tumor-related features RNA-seq analysis will be carried out on these surgical samples aiming at confirming the results of the exploratory analysis and refine the gene expression profile In this subset the enrolment of patients who underwent neoadjuvant treatment will be allowed
Due to the limited number samples from patients affected by ampullary adenocarcinoma with favorable prognosis will be analyzed in one step and compared to matched cases with unfavorable prognosis 8 patients each group C
Following the identification of gene expression profiles both for pancreatic and ampullary adenocarcinoma an external validation set will be enrolled in order to perform RNA-seq analysis on additional 60-80 surgical samples from other institutions and validate the prognostic relevance of the identified pattern in predicting a less aggressive disease course
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