Systematic Evaluation of Human Explant Model Systems Engineering (SEEDLING)

All current forms of therapy for tumor patients are essentially based on clinical, genomic or histopathological criteria for the choice of therapy. However, the change in the tissue during therapy is of particular importance for patients, both with regard to the development of resistance and the side effect profile. This applies in particular to immunotherapies and their use in advanced tumor diseases. Preliminary work on the fully human tumor explant model has shown that the use of human donor tissue in the context of a special bioreactor makes it possible to improve the possibilities of predicting and better understanding the mechanism of action of a therapeutic agent. Since there is a considerable need for personalized and thus improved therapy management in the field of oncology, the aim of this study is on the one hand to improve the decisive tissue parameters for the cultivation of human donated material and on the other hand to understand the basic reaction patterns of the tissue to therapies.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult

Detailed Description

Personalized therapy is still one of the great goals of oncology. In view of the success of checkpoint inhibitor therapies in selected solid tumors, the question remains why other tumor diseases do not respond in the same way to the therapy. However, this is not only limited to immunotherapies. In principle, the understanding of the dynamic changes in a patient's tissue has so far been very limited, both for predicting a therapy success and with regard to the mechanistic understanding of how a therapy works. Model systems for diseases are often animal models that reproduce the complexity of a multi-organ system, but show significant differences to humans at the tissue level and therefore have only little informative value. Cell culture experiments, on the other hand, have only little informative value with regard to the overall behavior of a tissue or even an organ or the disease situation. "Naturalistic" co-culture in the Petri dish (such as with organoid systems) does not allow any sensible transferable insights, even if complex cell compositions of fibroblasts, endothelium or immune cells are used. In contrast, there is another problem for in vivo tumor models: either there is a lack of flexibility with regard to the structural context or the species-specific system properties do not allow any conclusions to be drawn about the situation in humans. This is a massive limitation, especially for translational studies. The Tumor Explant Model System developed by us allows the structural integrity of the tissue context to be maintained in the context of obtaining a biopsy or removing a resection. The tissue sample obtained in this way is kept in equilibrium via a bioreactor and can thus be used for tests or is preserved in its context of the tissue. It is also possible in the sense of a personalized diagnosis and therapy to take into account the individual bandwidth of the composition of the tumor microenvironment. This approach has already been validated in a prospective study and the transferability of the results from the explant models to humans has been proven. In this situation, the systematic construction of explant models for other tumor entities and the use of these models for therapy development and for better understanding of pathoregulation in tissues. In addition to the tissue samples donated by the study participants, blood cells can also be used for testing the tissue.hand to understand the basic reaction patterns of the tissue to therapies.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Azaz Ahmed, Dr. med.; Phone Number: +49-6221-56-7229; Email: Azaz.Ahmed@med.uni-heidelberg.de
• Study Contact Backup: Name: Niels Halama, Dr. med.; Phone Number: +49-6221-56-4801; Email: Niels.Halama@nct-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University of Heidelberg / NCT
    • Contact: Azaz Ahmed, Dr. med.; Phone Number: +49-6221-56-7229; Email: Azaz.Ahmed@med.uni-heidelberg.de
    • Contact: Niels Halama, PD Dr. med; Phone Number: +49 6221-56-7229; Email: Niels.Halama@med.uni-heidelberg.de
    • Sub-Investigator: Anja Williams, Dr.
    • Sub-Investigator: Axel Benner

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All patients with solid tumor diseases in a non-curative setting.

Description

Inclusion Criteria:

• Tissue material for Explant Model generation available or accessible

Exclusion Criteria:

• curatively resected/treated tumors

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue Biopsy Specimen vs Tumor Explant Model Prediction	Comparison of serial biopsy measurements to Explant Model measurements in the context of individual Patient variability, Serial biopsy timepoints can vary between 1 day up to 24 weeks	up to 24 weeks

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Collaborators: German Cancer Research Center
• Investigators: Study Chair: Dirk Jaeger, Prof. Dr. med., University Hospital Heidelberg

Publications and helpful links

General Publications

• Halama N, Zoernig I, Berthel A, Kahlert C, Klupp F, Suarez-Carmona M, Suetterlin T, Brand K, Krauss J, Lasitschka F, Lerchl T, Luckner-Minden C, Ulrich A, Koch M, Weitz J, Schneider M, Buechler MW, Zitvogel L, Herrmann T, Benner A, Kunz C, Luecke S, Springfeld C, Grabe N, Falk CS, Jaeger D. Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients. Cancer Cell. 2016 Apr 11;29(4):587-601. doi: 10.1016/j.ccell.2016.03.005.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: November 11, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: chemotherapy; metastases; immunotherapy; cancer; radiation; targeted therapy
• Other Study ID Numbers: U1111-1254-2831-S-507/2019; U1111-1254-2831 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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