Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients With Pancreatic Cancer (SUCCESS)

January 27, 2019 updated by: alina constantin, Ponderas Academic Hospital

PD-L1 and MMR Status Provided by Endoscopic Ultrasound-Guided Fine-Needle Biopsies as a Predictor of PrognosiS in Patients With Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has a suboptimal response to standard therapies that modestly impact survival due to its ability to evade host immune surveillance. Emerging evidence has shown that the co-inhibitory receptors, such as programmed death 1 (PD-1), play a critical role in cancer immune-editing. Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. The advent of immunotherapy, with checkpoint inhibitors, which block PD-L1 interaction between tumor cells and activated T cells, has significantly altered the treatment algorithm for several solid tumors.

However, the clinicopathologic significance and prognostic value of PD-L1 in PDAC remains controversial. The main technical ground may be that PDAC PD-L1 expression quantification is limited to surgical resection specimens and dependent on specific immunohistochemistry (IHC) tests. In addition, PD-L1 expression has not been extensively assessed before surgery in treatment-naive PDAC patients, due to the current IHC test requirement for a histologic rather than a cytologic evaluation. However, a recent study showed that EUS-fine needle biopsy (FNB) can successfully determine primary pancreas malignancy PD-L1 status.

One recently identified subtype within the genomic landscape of PDAC is the mismatch repair-deficient (dMMR) tumor. Evaluation of dMMR status is particularly important following the FDA approval of the PD-1 inhibitor, pembrolizumab, for the treatment of unresectable or metastatic, microsatellite instability-high (MSI-H) or dMMR PDAC that have progressed following prior treatment, and have no satisfactory alternative treatment options.

The objectives of the project will include the assessment of tumor PD-L1/dMMR expression in patients with PDAC using EUS-FNB samples and the prospective correlation of MMR status and PD-L1 expression with overall survival and progression-free survival of PDAC patients.

Study Overview

Status

Unknown

Conditions

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with a confirmed diagnosis of pancreatic ductal adenocarcinoma

Description

Inclusion Criteria

  • Age 18 to 90 years old
  • men or women
  • signed informed consent for EUS and EUS -FNB
  • the diagnosis of adenocarcinoma histologically confirmed by FNB
  • resectable, Unresectable, locally advanced and/or metastatic disease

Exclusion Criteria:

-previous chemotherapy or radiotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PATIENTS WITH PANCREATIC CANCER

All patients with a suspicion of pancreatic masses will undergo EUS (including EUS-FNB for confirmation of diagnosis). A positive cytological diagnosis will be taken as a final proof of malignancy of the pancreas mass. The diagnoses obtained by EUS-FNB will be further verified during a clinical follow-up of at least 6 months.

Immunochemistry will be performed on the EUS-FNB specimens to determine PD-L1 expression and MMR status

EUS WITH EUS-FNB will be performed for confirmation of diagnosis and analysis of MMR status and PD-L1 expression

Protocol of EUS with EUS-FNB should include linear EUS instruments with complete examinations of the pancreas. Tumor characteristics (echogenicity, echostructure, size) will be described as well as presence/absence of power Doppler signals.

EUS-FNB will be performed in all pancreatic masses with at least three passes in the absence of an onsite cytopathologist using a fanning technique with a 22-gauge needle (SharkCore FNB needle Medtronic Corp. or Acquire FNB needle Boston, MA).

IHC will be performed on treatment-naïve formalin-fixed paraffin-embedded EUS-FNB pancreatic specimens. Briefly, 4-μm-thick tissue sections will be stained using the Ventana BenchMark XT automated slide-staining system using the following antibodies: Anti-PD-L1 (clone SP263, VENTANA, Tucson, AZ), MLH1 (clone G168-728, Cell Marque, Rocklin, California, United States), MSH2 (clone FE11, Biocare Medical, Concord, Massachusetts, United States), MSH6 (clone BC/44, Biocare Medical, Concord, Massachusetts, United States), and PMS2 (clone A16-4, Biocare Medical, Concord, M Massachusetts, United States). Antigen-antibody reactions will be visualized using UltraView detection with diaminobenzidine as the chromogen. The specimen will be considered to have PD-L1 expression if PD-L1 is expressed in ≥ 1 % of tumor cells and a high level of expression if ≥ 50 %. Tumors will be classified as dMMR if they exhibit absent nuclear staining of DNA mismatch repair proteins (MLH1, MSH2, MSH6, or PMS2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of PD-L1 expression analysis on EUS-FNB pancreatic specimens
Time Frame: 1 year
the percentage of cases where EUS-FNB material was adequate to determine PDL-1 expression
1 year
Feasibility of MMR status analysis on EUS-FNB pancreatic specimens
Time Frame: 1 year
the percentage of cases where EUS-FNB material was adequate to determine MMR status
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor response
Time Frame: 3 months
Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). According to RECIST guidelines,complete response (CR) is defined as the complete disappearance of the tumor, partial response (PR) as ≥30% decrease in longest diameter (LD), progressive disease (PD) as ≥20% increase in LD, and stable disease (SD) as a decrease or increase less than PR or PD based on anatomic assessment. Patients with CR or PR will be defined as responders, whereas those with PD or SD are defined as non-responders.
3 months
Overall survival
Time Frame: up to 12 months
The overall survival will be measured from the day of diagnosis to the date of death
up to 12 months
Progression-free survival
Time Frame: up to 12 months
The progression-free survival (PFS) will be measured from the day of diagnosis to the date of progressive disease.
up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

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 Major Dates

Study Start (Anticipated)

February 1, 2019

Primary Completion (Anticipated)

January 1, 2021

Study Completion (Anticipated)

January 1, 2022

Study Registration Dates

First Submitted

December 30, 2018

First Submitted That Met QC Criteria

January 27, 2019

First Posted (Actual)

January 29, 2019

Study Record Updates

Last Update Posted (Actual)

January 29, 2019

Last Update Submitted That Met QC Criteria

January 27, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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