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

January 15, 2021 updated by: J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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

Intervention / Treatment

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1100 DD
        • Recruiting
        • Academic Medical Center, Medical Oncology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Time Frame: 2 months

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.
Time Frame: 2 months
Similarly to our primary study parameter, the value of prediction for a biomarker will be assessed.
2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Collaborators

Erasmus Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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