Clinical trial NCT03820921: Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients With Pancreatic Cancer
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pancreatic Cancer
Keywords: EUS-FNB, PDL1, MMR
Lead sponsor: Ponderas Academic Hospital
Sponsor class: OTHER
Collaborators: name: University of Medicine and Pharmacy Craiova
First posted: 2019-01-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a confirmed diagnosis of pancreatic ductal adenocarcinoma

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of PD-L1 expression analysis on EUS-FNB pancreatic specimens
timeFrame: 1 year
measure: Feasibility of MMR status analysis on EUS-FNB pancreatic specimens
timeFrame: 1 year
Secondary outcomes:
measure: Tumor response
timeFrame: 3 months
measure: Overall survival
timeFrame: up to 12 months
measure: Progression-free survival
timeFrame: up to 12 months
Other outcomes:
Locations:
Study officials:
References: