Establishing Organoids From Metastatic Pancreatic Cancer Patients, the OPT-I Study. (OPT-1)

Establishing Organoids From Metastatic Pancreatic Cancer Patients, the OPT-I Study

Rationale: Pancreatic adenocarcinoma is a malignancy with a poor prognosis. Resection is the only curative option and still 5-year survival rate is less than 10 percent. However, most patients present with advanced disease and are provided with palliative care. The nature of the tumour and the intense stromal reaction around the tumour cells leave pancreatic adenocarcinoma relatively insensitive to chemotherapeutics. Current models, such as cell lines or patient derived xenografts, cannot provide predictive information in a clinically relevant timeframe. Organoids and organotypic culture systems have emerged as promising new culturing techniques that maintain some of the complexity of the tumour. As most patients are ineligible for tumour resection, this project will focus on metastases and will generate organoids from that tissue. Using a combination of organoids and organotypic systems, treatment (non)response can be predicted, which may provide a personalized treatment setting for patients with advanced pancreatic adenocarcinoma.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Pancreatic Ductal
• Intervention / Treatment: Diagnostic test: biopsies & blood analyses

Detailed Description

Rationale: Pancreatic adenocarcinoma is a malignancy with a poor prognosis. Resection is the only curative option and still 5-year survival rate is less than 10 percent. However, most patients present with advanced disease and are provided with palliative care. The nature of the tumour and the intense stromal reaction around the tumour cells leave pancreatic adenocarcinoma relatively insensitive to chemotherapeutics. Current models, such as cell lines or patient derived xenografts, cannot provide predictive information in a clinically relevant timeframe. Organoids and organotypic culture systems have emerged as promising new culturing techniques that maintain some of the complexity of the tumour. As most patients are ineligible for tumour resection, this project will focus on metastases and will generate organoids from that tissue. Using a combination of organoids and organotypic systems, treatment (non)response can be predicted, which may provide a personalized treatment setting for patients with advanced pancreatic adenocarcinoma.

Objective: To develop a model system and infrastructure to individualize the treatment of patients with advanced pancreatic adenocarcinoma. Additionally, we aim to identify predictors of therapy (non)response.

Study design: Observational laboratory studies (with DNA/RNA isolation, RNA sequencing, cell culturing, organoid culturing and xenografting) will be performed with tumour specimens. These organoids will be stored for future research.

Study population: All adult patients (> 18 years) with (a suspicion of) advanced pancreatic adenocarcinoma

Main study parameters/endpoints: The development of organoids from biopsies of metastases or primary tumour tissue of pancreatic cancer that correlate with clinical response. These models are then analysed for the expression of bio markers in organoid, organotypic and xenograft models. DNA/RNA profiles will be correlated to clinical and pathological characteristics such as therapy response, survival and TNM classification.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participating in this study requires a biopsy from the patient. The material will be obtained from the biopsy required for diagnosis or the patient is asked for consent for an additional tumor biopsy not required for diagnosis. The study could benefit patients as their organoids can be used to assess efficacy of first-line treatment and when necessary may provide an advice for second-line treatment options. Additionally, patients may benefit in the future, if biomarkers are found to predict therapy (non)response.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: M G van Mackelenbergh; Phone Number: 020-5665955; Email: m.g.vanmackelenbergh@amc.nl
• Study Contact Backup: Name: J W Wilmink, M.D. PhD; Phone Number: 020-5665955; Email: j.w.wilmink@amc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1100 DD
    • Recruiting
    • Academic Medical Center, Medical Oncology
    • Contact: J. W. Wilmink, MD, PhD, PhD; Phone Number: 31 20 5665955; Email: j.w.wilmink@amc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years
• Diagnosed with locally advanced pancreatic cancer or metastatic pancreatic cancer
• Able to understand the information given
• WHO 0-2

Exclusion Criteria:

• Unfit for biopsies & blood analyses
• Not able to give informed consent (language, intellectual capacities, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Developing organoids from advanced pancreatic cancer patients that predict non response or response	To assess whether there is a correlation between no response in patients and no response in organoids, a goodness of fit will be determined with Pearson's X2 test. Depending on the available data, the second scenario will be analysed similarly. When organoids cannot be established from biopsy material, then this will be recorded and linked to clinical parameters.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional studies will be done with the patient derived organoids to find biomarkers that correlate with response in organoids and patients.	Similarly to our primary study parameter, the value of prediction for a biomarker will be assessed.	2 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 4, 2017
• Primary Completion (ANTICIPATED): September 1, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (ACTUAL): April 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pancreatic cancer; Organoids
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: 2017-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No