Clinical trial NCT05927298: Province of Ontario Strategy for Personalized Management of Pancreatic Cancer Trial
Official title: Province of Ontario Strategy for Personalized Management of Pancreatic Cancer Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreas Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Ontario Institute for Cancer Research
name: Ottawa Hospital Research Institute
name: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
First posted: 2023-07-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Upfront resectable PDAC not receiving neoadjuvant chemotherapy (Immunotherapy only regimens are eligible)
2. Advanced (unresectable or metastatic) PDAC suitable for systemic therapy.

Brief summary: This is a prospective, multi-centre, translational and observational study. Two cohorts of patients with pancreatic ductal adenocarcinoma (PDAC) are eligible to enroll 1) Upfront resectable PDAC 2) Advanced (unresectable PDAC or metastatic). Patients will have tissue either at resection or from a biopsy at enrolment processed for whole genome sequencing, RNA sequencing and for establishment of patient derived organoids (PDOs). Background epidemiological history and outcome data will be prospectively annotated. Serial blood and stool samples will be collected for exploratory analyses. All electronic medical record information will also be collected. Data will be used to determine if an integrated correlative analysis of whole genome sequencing/RNAsequencing (WGS/RNAseq) and PDOs in the enrolled population will increase the number of patients receiving a precision-matched treatment in Ontario

Detailed description: This study is being done to answer the following question: Can creating 3D models using tumour samples and looking at genetic information from pancreatic ductal adenocarcinoma (PDAC) tumours, help us to provide more patients with a specific, personalized treatment? Two groups of patients with PDAC are eligible to enroll 1) PDAC patients that will go straight to surgery 2) PDAC patients where the disease is either too advanced for a surgical option, or the disease has spread to other areas in the body. Patients will have tumour tissue taken either during their surgery or from a biopsy at enrolment. Background history, outcome data, questionnaires, series of blood draws and stool samples will be collected for analyses. All electronic medical record information will also be collected.

Researchers are looking for better ways of understanding and treating pancreatic cancer by looking to see how useful it is to know about changes and characteristics in the genes in the tumour (molecules that contain instructions for the development and functioning of the cells). Results from analyzed data may be useful in choosing treatments for enrolled patients and for patients in the future. Patients current treatment plan will not change if they choose to take part in this study.

Eligibility criteria: Inclusion Criteria:

1. Patients must have either upfront resectable PDAC or advanced (unresectable or metastatic) PDAC (borderline PDAC and those planned for neoadjuvant chemotherapy excluded)
2. Patients with a histological or radiological diagnosis of pancreatic ductal adenocarcinoma (PDAC). For patients awaiting histological confirmation, tissue obtained at study enrolment or can suffice. For those patients who undergo a resection, surgical tissue will be used.
3. For patients enrolling with resectable PDAC (cohort 1) - the definition of resectability will be according to NCCN guidelines and the patient must be planned for a surgery first approach.
4. For patients with advanced PDAC (cohort 2), all stages are eligible including locally advanced unresectable, first-line metastatic, second-line (or beyond) metastatic.
5. In advanced PDAC patients (cohort 2) where a single lesion is to be biopsied, the lesion should be amenable to a core needle biopsy as judged by a staff radiologist. A minimum of 4 to 6 x 18 Gauge (G) good quality tumour cores must be safely obtainable under CT or US guidance.
6. Patients must have a life expectancy of ≥ 6 months
7. ECOG 0-1
8. Patient must be suitable for systemic therapy
9. Patients should have organ function deemed sufficiently adequate to receive systemic therapy

Exclusion Criteria:

1. Certain histologies are excluded: colloid, high grade neuroendocrine;
2. For patients enrolling in cohort 2 - Patients without a tumour lesion amenable to biopsy or with tumour lesions that are not safe for sampling a minimum of 4 to 6 x 18G good quality tumour cores by image guided core needle biopsy as judged by a staff radiologist.
3. Patients who are not fit enough to undergo a tumour biopsy for any reason as judged by the investigator; this includes patients who cannot stop anticoagulation therapy.
4. For cohort 1 - patients receiving neoadjuvant chemotherapy are excluded, (neoadjuvant immunotherapy is permitted)

Primary outcomes:
measure: Precision-Matched Treatment Utilization Rate
timeFrame: 4 years
Secondary outcomes:
measure: Build a comprehensive dataset of pancreatic cancer specimens (tissue and blood) and matched patient-derived organoids (PDOs)
timeFrame: 4 years
measure: Correlate drug sensitivities in patient-derived organoids (PDOs) and molecular information
timeFrame: 4 Years
measure: Correlate immune phenotypes and molecular profiles
timeFrame: 4 Years
Other outcomes:
measure: Develop an electronic medical record (EMR) platform utilizing artificial intelligence (AI) modeling
timeFrame: 4 Years
measure: Correlate serial plasma whole-genome sequencing (WGS) and tissue WGS
timeFrame: 4 Years
measure: Characterize the epigenome in established patient-derived organoids (PDOs)
timeFrame: 4 Years
measure: Assess oncolytic virus efficacy in combination with immune checkpoint inhibitors in a subset of 50 patient-derived organoids (PDOs) co-cultured with autologous peripheral blood mononuclear cells (PBMCs)
timeFrame: 4 Years
measure: Identify microbiome differences in patients at various stages of pancreatic ductal adenocarcinoma (PDAC) and their correlation with whole-genome sequencing (WGS)/RNA subtypes
timeFrame: 4 Years
measure: Document stroma subtypes in pancreatic cancer and their correlation with clinical outcomes
timeFrame: 4 Years
measure: Evaluate treatment responses in patients receiving precision-matched treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
timeFrame: 4 Years
measure: Investigate the involvement of genetic and environmental factors in the development and progression of pancreatic cancer
timeFrame: 4 Years
measure: Assess comparability between WGS and commercial panel
timeFrame: 4 Years
measure: Explore the feasibility and efficacy of utilizing digitized whole-slide images of biopsy or resection specimens for an AI-based digital pathology prediction system
timeFrame: 4 Years
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Erica Tsang, MD
role: PRINCIPAL_INVESTIGATOR
References: