Prospective Evaluation of MRI Biomarkers in Pancreatic Ductal Adenocarcinoma

Assessing the Utility of Macromolecular Dynamic Contrast Enhanced MRI and Diffusion Weighted Imaging as Biomarkers for Vascular Permeability and Fibrosis in Pancreatic Cancer

This is a prospective cohort study in participants with pancreatic adenocarcinoma who are undergoing surgical resection. Participants will have up to two magnetic resonance imaging (MRI) scans with and without intravenous contrast. The MRI will be performed using either an extracellular contrast agent or using a macromolecular contrast agent. These contrast agents are routinely used in body MRI and are on formulary at this institution. Parameters will be compared to histopathology measures of mean vascular density and grade of fibrosis, respectively. The purpose is to establish a standard protocol for future clinical trials of treatments that would use MRI parameters as quantitative markers of treatment effect.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Other: MRIs with and without intravenous contrast (up to 2)

Detailed Description

This is a prospective cohort study of dynamic contrast enhanced MRI (DCE-MRI), which includes diffusion weighted imaging (DWI-MRI) in participants with pancreatic adenocarcinoma who are undergoing surgical resection. Participants will have up to two MRI scans with and without intravenous contrast. The MRI will be performed using either an extracellular contrast agent or using a macromolecular contrast agent. These contrast agents are routinely used in body MRI and are on formulary at this institution. Quantitative parameters of volume transfer coefficient (Ktrans) and apparent diffusion coefficient (ADC) will be calculated from the MRI sequences and each parameter will be compared to histopathology measures of mean vascular density and grade of fibrosis, respectively. The influence of the contrast agent (extracellular and macromolecular) on agreement between imaging parameters and histopathology will be assessed and agreement in Ktrans as derived from a one compartment and a two-compartment model will be assessed. If a participant is unable to receive intravenous contrast due to renal dysfunction or refuses IV contrast, the non-contrast portion of the exam will be used for analysis. The purpose is to establish a standard protocol for future clinical trials of treatments that would use MRI parameters as quantitative markers of treatment effect.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. > 18 years of age.
2. Biopsy proved pancreatic ductal adenocarcinoma (PDA) and/or a pancreatic mass with imaging features suggestive of pancreatic adenocarcinoma planned for surgical resection.
3. No contraindication to MRI such as severe claustrophobia (not alleviated by oral anti-anxiolytics) or metal/mechanical devices in their body not considered magnetic resonance (MR) compatible at 1.5 Tesla (departmental MRI safety screening form)
4. No known allergy to gadolinium based contrast agent
5. For contrast enhanced studies, participant has an estimated glomerular filtration rate (GFR) >30 mg/dL using the modification of diet in Renal Disease (MDRD) formula. If the participant has an estimated GFR ≤30 mg/dL, they can still participate but no intravenous contrast will be administered.

Exclusion Criteria:

1. Contraindication to MR imaging
2. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy Volunteers; Normal volunteers with no pancreas mass or risk factors for pancreas cancer will be recruited for MRI protocol optimization and nothing more. No intravenous contrast will be given. They will be asked to lie in the scanner for up to 1 hour and non-contrast imaging will be performed.
Experimental: Pancreatic Mass or Risk Factors Group; Participants with pancreatic adenocarcinoma who are planning to undergo surgical resection. Participants will undergo up to two MRIs with and without intravenous contrast. The first MRI will be performed using an extracellular contrast agent and the second 1-14 days later, with a macromolecular contrast agent. If patient cannot undergo the second MRI for any reason eg. not enough time before surgery, one MRI with either contrast agent will still be used for analysis .	Other: MRIs with and without intravenous contrast (up to 2); Participants will undergo up to two MRIs with and without intravenous contrast. The first MRI will be performed using an extracellular contrast agent and the second 1-14 days later, with a macromolecular contrast agent. If patient cannot undergo the second MRI for any reason eg. not enough time before surgery, one MRI with either contrast agent will still be used for analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlation between Apparent Diffusion Coefficient (ADC) of pancreatic cancer based on MRI with percent fibrosis at histopathology	One year

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between Ktrans of pancreatic cancer derived from dynamic contrast enhanced MRI performed with gadopentetate dimeglumine and mean vascular density quantified at histopathology.	Two years

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Lyndon Luk, MD, CUIMC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 10, 2021

Study Registration Dates

• First Submitted: February 25, 2015
• First Submitted That Met QC Criteria: May 14, 2016
• First Posted (Estimated): May 18, 2016

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Pancreatic Adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: AAAL2505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED