A Prospective Translational Tissue Collection Study in Early and Advanced Pancreatic Ductal Adenocarcinoma and Pancreatic Neuroendocrine Tumours to Enable Further Disease Characterisation and the Development of Potential Predictive and Prognostic Biomarkers (PaC-MAn)

A Prospective Translational Tissue Collection Study in Early and Advanced Pancreatic Ductal Adenocarcinoma (PDAC) and Pancreatic Neuroendocrine Tumours (PanNETs) to Enable Further Disease Characterisation and the Development of Potential Predictive and Prognostic Biomarkers

There are several types of early pre-cancerous lesions found in the pancreas which have the potential to develop into pancreatic cancer. Although different patients' pancreatic cancers or pre-cancerous pancreatic lesions have many similarities we believe that subtle differences can affect how they behave and therefore influence individual patient outcomes. Many factors may account for the differences seen in pancreatic lesion behaviour, for example molecular and genetic differences (the DNA and RNA present which control how a cell grows and divides), differences in how the immune system responds to the lesion, differences in the environment immediately around the lesion in the pancreas, known as the tumour microenvironment and differences in the micro-organisms which colonize a particular patient, known as their microbiota .

This project studies the molecular makeup of pancreatic lesions and their microenvironment at various stages (from pre-cancerous lesions all the way through to more advanced disease) to see if we can use this information to divide patients into different groups whose lesions may behave in similar ways. We will be trying to find out if there are molecular reasons why some patients respond to particular treatments when others do not, why some patients experience more toxicity with particular treatments and why some patients' disease behaves particularly aggressively when other patients' disease does not. We will also be investigating the particular micro-organisms colonizing individual patients to see if these impact a patient's outcome. Understanding what makes one person's pancreatic lesion behave differently to another's could lead to better treatment, where a personalized therapeutic strategy could be applied for every single patient.

Study Overview

• Status: Unknown
• Conditions: Pancreatic Adenocarcinoma

Detailed Description

The main objective is to describe the incidence and distribution of tumour biomarkers, and to identify molecular subgroups from a multicentre series of patients who are investigated for and subsequently diagnosed with a pancreatic adenocarcinoma (PDAC) or a precursor lesion or a pancreatic neuroendocrine tumour.

The secondary objective is to determine disease control rate (CR, PR and SD >24 weeks), duration of response, progression free survival (PFS) and overall survival (OS) in locally advanced / metastatic patients or relapse free survival (RFS) and overall survival (OS) in early stage curative / pre-cursor lesion patients, associated with the identified molecular subtypes of PDAC pancreatic cancer and relevant anti-cancer therapies.

To identify molecular predictors of response or toxicity to standard of care anti-cancer therapies in PDAC/PanNET. The study also has a number of exploratory objectives listed below:

Depending on the number of patients assessable for each biomarker of interest and the prevalence of biomarker expression in the study population, exploratory endpoints of this study include:

1. Evaluation of the predictive value of biomarker expression (i.e. the ability of a biomarker to predict responsiveness or resistance to a specific anti-cancer treatment).
2. Evaluation of the prognostic value of biomarker expression (i.e. the ability of a biomarker to predict outcome regardless of a specific anti-cancer treatment).
3. Comparison of biomarker expression among IPMN, MCN, and pancreatic adenocarcinoma and evaluation of their prognostic value.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Recruiting
      • The Royal Marsden NHS Foundation Trust
      • Contact: Bijal Patel; Phone Number: 4450 02086426011; Email: bijal.patel@rmh.nhs.uk
      • Sub-Investigator: David Lau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

early/advanced pancreatic adenocarcinoma or a precursor lesion or a pancreatic neuroendocrine tumour.

Description

Inclusion Criteria:

1. Patient is being investigated or treated for pancreatic cancer or precursor lesions at The Royal Marsden Hospital and referring centres during the study period.
2. Patient has a histologically/cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma, or pancreatic neuroendocrine tumour OR Patient has a tissue lesion suspicious for pancreatic cancer amenable to core needle biopsy or surgery and is clinically fit enough to undergo a tumour biopsy or surgery according to investigator assessment and local guidelines.
3. Patient is ≥ 18 years of age.
4. Patient can understand the patient information sheet and is able to provide written informed consent.
5. Patient has sufficient tissue and/or blood and/or urine and/or stool and/or saliva sampling for analysis as per the protocol.

Exclusion Criteria:

1. Patients who are not treated at all at The Royal Marsden Hospital or referring centre.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pancreatic Cancer; Patients who are investigated for and subsequently diagnosed with early/advanced pancreatic adenocarcinoma or a precursor lesion or a pancreatic neuroendocrine tumour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to describe the incidence and distribution of biomarkers and identify molecular subtypes in a large, multi-centre, series of patients with pancreatic cancer and precursor lesions.	Blood, urine, stool, saliva, bile and tissue samples from patients undergoing a tissue biopsy or surgery for suspected or known pancreatic cancer will be collected	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the incidence and distribution of biomarkers and identify molecular subtypes in a large, multi-centre, population of patients with pancreatic cancer or precursor lesions.	Molecular analyses including, but not limited to, miRNA analysis, DNA and RNA sequencing, nanostring, RT-PCR and immunohistochemistry will be carried out.	4 years
To identify molecular predictors of response or toxicity to standard of care anti-cancer therapies in PDAC/PanNET.	Blood, urine, stool, saliva, bile and tissue samples from patients undergoing a tissue biopsy or surgery for suspected or known pancreatic cancer will be collected. Molecular analyses including, but not limited to, miRNA analysis, DNA and RNA sequencing, nanostring, RT-PCR and immunohistochemistry will be carried out.	4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depending on the number of patients assessable for each biomarker of interest and the prevalence of biomarker expression in the study population, exploratory endpoints of this study include	evaluation of the predictive value of biomarker expression (i.e. the ability of a biomarker to predict responsiveness or resistance to a specific anti-cancer treatment).	4 years
Depending on the number of patients assessable for each biomarker of interest and the prevalence of biomarker expression in the study population, exploratory endpoints of this study include	evaluation of the prognostic value of biomarker expression (i.e. the ability of a biomarker to predict outcome regardless of a specific anti-cancer treatment).	4 years
Depending on the number of patients assessable for each biomarker of interest and the prevalence of biomarker expression in the study population, exploratory endpoints of this study include	comparison of biomarker expression among IPMN, MCN, and pancreatic adenocarcinoma and evaluation of their prognostic value.	4 years

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Investigators: Study Chair: David Cunningham, The Royal Marsden Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Anticipated): January 10, 2023
• Study Completion (Anticipated): January 10, 2023

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adenocarcinoma; Neuroendocrine Tumors
• Other Study ID Numbers: CCR4753

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No