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

Pancreatic Cancer Clinical Trial

— SUCCESS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03820921
• Other study ID #: SUCCESS
• Status: Not yet recruiting
• Start date: February 1, 2019
• Est. completion date: January 1, 2022

Study information

• Verified date: January 2019
• Source: Ponderas Academic Hospital
• Contact: Alina L Constantin, MD
• Phone: +40722468415
• Email: drconstantinalina[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Diagnostic Test:
• EUS-FNB
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).

Other:
• Immunohistochemistry
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).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Ponderas Academic Hospital	University of Medicine and Pharmacy Craiova

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of PD-L1 expression analysis on EUS-FNB pancreatic specimens	the percentage of cases where EUS-FNB material was adequate to determine PDL-1 expression	1 year
Primary	Feasibility of MMR status analysis on EUS-FNB pancreatic specimens	the percentage of cases where EUS-FNB material was adequate to determine MMR status	1 year
Secondary	Tumor response	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
Secondary	Overall survival	The overall survival will be measured from the day of diagnosis to the date of death	up to 12 months
Secondary	Progression-free survival	The progression-free survival (PFS) will be measured from the day of diagnosis to the date of progressive disease.	up to 12 months