Clinical trial NCT03001518: Immunologic Signatures Following Surgery for Pancreatic Cancer
Official title: Immunologic Signatures Following Surgery for Pancreatic Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pancreatic Cancer
Surgery
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2016-12-23
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with pancreatic ductal adenocarcinoma who undergo surgical resection of the cancer, with or without irreversible electroporation.

Brief summary: The goal of this pilot study is to evaluate and describe the immunologic and overall outcomes of subjects who undergo routine pancreatectomy with or without irreversible electroporation (IRE) for pancreatic cancer. Immunologic markers in the blood will be measured at several time points before and after surgery to determine if surgical approach is associated with different immunologic responses. Secondary outcomes will include mortality and morbidity; operative time; blood loss and transfusion requirements; and oncologic outcomes such as: margin status, lymph node harvest, disease-free survival, and overall survival. Analysis of immune response will help the investigator determine whether to expand the pilot into a larger study.

Detailed description: Subjects will have blood draws at the following timepoints: Pre-op, 1-2 days post-op, 3-5 days post-op, and 1-4 months post-op. At each timepoint, three 8.5mL ACD (yellow top) vacutainer tubes will be drawn by the Biobank and Translational Research Core (BRTC), study personnel, or hospital phlebotomists. The blood will be processed for PBMC isolation by BRTC for Dr. Weinhold's laboratory and will be viable within 8 hours of draw. These timepoints for blood draws are at the same time as usual operative care and will not require additional visits on the part of the subject.

For this study we will extensively utilize several polychromatic flow cytometry (PFC) platforms to follow activation, maturation, exhaustion, and proliferation patterns within CD4+ and CD8+ subsets of T-cells. We will also utilize an intracellular cytokine staining (ICS) platform in efforts to detect anti-tumor associated antigen (TAA) responses by CD4+ and CD8+ T cells from peripheral blood mononuclear cells (PBMC) as well as lymphocytes infiltrating the patient's tumor. These assays are designed to measure antigen-driven intracellular production of IFN-γ, TNF-α, and IL-2, as well as the degranulation marker CD107. This strategy enables us to not only document individual cytokine responses, but to also assess (through Boolean gating) changes in relative polyfunctionality of the responses.

Eligibility criteria: Inclusion Criteria:

* Subject must be at least 18 years of age and at least the minimum age of majority according to applicable State or Country Law.
* Subject is a suitable surgical candidate, i.e., is able to undergo general anesthesia and pancreatectomy for diagnosis of cancer
* Subject is willing and able to undergo additional blood draws

Exclusion Criteria:

• Subject is not a suitable candidate for surgery, or surgery is unable to be completed

Primary outcomes:
measure: immune response
timeFrame: preoperatively to 3 months postoperatively
Secondary outcomes:
measure: 90-day mortality
timeFrame: 90 days
measure: surgical-site infection (SSI)
timeFrame: 90 days
measure: pancreatic leak by qualitative appearance or amylase level
timeFrame: 90 days
measure: operative time
timeFrame: 1 day
measure: use of neoadjuvant therapy
timeFrame: 1 day
measure: use of adjuvant therapy
timeFrame: 90 days
measure: CA 19-9 level
timeFrame: 90 days
measure: return to operating room
timeFrame: 90 days
measure: Non-SSI infection
timeFrame: 90 days
measure: margin status
timeFrame: 1 week
measure: intraoperative transfusion
timeFrame: 1 day
measure: lymph node status
timeFrame: 1 week
measure: overall survival
timeFrame: 5 years
measure: disease-free survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: Sabino Zani, MD
role: PRINCIPAL_INVESTIGATOR
References: