The goal of this study is to learn if the genetic information and proteins from tumours can help treat pancreatic ductal adenocarcinoma (PDAC). The main questions it aims to answer are:

• Is it feasible to obtain genetic test results within a timeframe that can help inform treatment decisions for individuals with PDAC?
• Can the genetic test results provide information about how a tumour will respond to or resist treatment?

Participants will:

• Receive standard chemotherapy to treat their cancer.
• Provide samples of their blood, tissue, and fluid for genetic testing.
• Visit the clinic every 4 weeks for check-ups and tests.
• Complete questionnaires every 12 weeks.

Inclusion Criteria:

Participants must meet all of the following criteria prior to Pre-Baseline registration:

1. Age 18 years or older.
2. Histological or radiological diagnosis of resectable, borderline resectable, or locally advanced PDAC.
3. Medically fit and planned to undergo laparoscopic procedure as part of standard of care.
4. Able to give informed consent for the study-related procedures performed during laparoscopy.

Participants must meet all of the following criteria to be eligible for enrollment in the Main Study:

1. Age 18 years or older.

2. Enrolled in the Personalized Oncogenomics (POG) Program at BC Cancer.

3. Histological and/or radiological diagnosis of resectable, borderline resectable, or locally advanced PDAC. Participants without a histological diagnosis of PDAC must undergo confirmatory histological diagnosis prior to treatment start date.

4. Medically fit to undergo surgical resection of the primary lesion(s) as judged by the investigator (Resectable and Borderline Resectable Cohorts only).

5. Planned for adjuvant (Resectable and Borderline Resectable Cohorts) or first-line (Locally Advanced Cohort) therapy with FOLFIRINOX or a gemcitabine-based regimen, either as part of routine care or in combination with an investigational agent(s) within another clinical trial. Participants may have received pre-operative therapy.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

7. Adequate organ function as defined by the following laboratory results obtained within 28 days prior to enrollment date:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.

   2. Hemoglobin ≥ 9 g/dL.

   3. Platelets ≥ 75 x 10^9/L.

   4. Prothrombin time test and international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x Upper Limit of Normal (ULN).

   5. Total bilirubin ≤ 1.5 x ULN. Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%.

   6. Aspartate aminotransferase (AST) and alanine aminotransferase (AST) ≤ 1.5 x ULN. If liver metastases are present, AST and ALT ≤ 5 x ULN is permitted.

   7. Albumin ≥ 25 g/L.

   8. One of the following:

      • Creatinine ≤ 1.5 x ULN.
      • Calculated creatinine clearance (as calculated by Cockcroft-Gault formula) ≥ 40 mL/min.
      • 24-hour urine creatinine clearance ≥ 40 mL/min.

8. Life expectancy greater than 90 days as judged by the investigator.

9. Able to give informed consent for the study procedures defined in this protocol.

10. Measurable disease by RECIST 1.1. For those in the Resectable and Borderline Resectable Cohorts, measurable disease must be present prior to resection surgery.

Exclusion Criteria:

1. Presence of distant or lymph node metastases. Individuals with metastatic PDAC are not eligible.
2. Currently receiving adjuvant (Resectable and Borderline Resectable Cohorts) or systemic (Locally Advanced Cohort) anti-cancer therapy (chemotherapy or any other anti-cancer agent) with one exception: pre-operative therapy is permitted.
3. Not fit for chemotherapy as judged by the investigator.
4. Presence of brain metastases.
5. Positive pregnancy test.
6. Unable to comply with the study assessments and procedures defined in this protocol.
7. Individuals who are otherwise judged by the investigator to be unfit to proceed with this protocol.