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2022-09-19
2023-05
2023-09
40
NCT05754788
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
OBSERVATIONAL
Gene Expression Profile of Resected Pancreatic and Ampullary Adenocarcinoma at Favorable Prognosis
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.
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 (RFS≥60 months) and unfavorable tumors (RFS<12 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.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2023-01-10 | N/A | 2023-05-25 |
2023-03-03 | N/A | 2023-05-26 |
2023-03-06 | N/A | 2023-05 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
N/A
Allocation:
N/A
Interventional Model:
N/A
Masking:
N/A
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| : Favorable-prognosis pancreatic adenocarcinoma Patients experiencing favorable prognosis (defined as RFS≥60 months) following resection for pancreatic adenocarcinoma | |
| : Unfavorable-prognosis pancreatic adenocarcinoma Patients experiencing unfavorable prognosis (defined as RFS<12 months) following resection for pancreatic adenocarcinoma |
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Favorable-prognosis gene expression pattern | Identification of DSP gene aberrations associated to favorable prognosis (≥60-month RFS) after radical surgery for pancreatic and ampullary adenocarcinoma, through comparison of prognostically favorable and unfavorable gene expression profiles found in different tumor and microenvironment compartments. | 19/09/2022-29/09/2023 |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| TCGA comparison | Comparison of the gene expression profile found at DSP with the TCGA database in order to confirm the clinical relevance of the identified gene expression pattern associated to prognostically favorable tumors | 19/09/2022-29/09/2023 |
| Clinical, biological and pathological factors | Identification of clinical, biological and pathological prognostic factors associated to favorable prognosis (≥60-month RFS) after radical surgery for pancreatic adenocarcinoma | 19/09/2022-29/09/2023 |
| External validation of gene expression profile | External validation of the identified gene expression profile through gene expression analysis of surgical samples from patients undergoing radical surgery for pancreatic adenocarcinoma in a different institution | 19/09/2022-29/09/2023 |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
