Tailoring Treatment in Colorectal Cancer (TargetCRC)
August 4, 2024 updated by: Sebastian Meltzer, University Hospital, Akershus
Pilot Study for Ex Vivo Tailoring of Treatment in Colorectal Cancer
In this study, the investigators will establish a reliable method and logistic pipeline for personalized drug testing ex vivo using fresh tumor samples from colorectal cancer (CRC) patients.
With this, the investigators aim to develop a novel predictive biomarker of immunotherapy response, by testing combinations of chemotherapies and chimeric antigen receptor (CAR) T cells.
Critically, this affects a large subgroup of patients currently not considered to benefit from such treatment.
To support the hypothesis, the project will make use of cutting-edge, cell-based functional diagnostics.
Individual patients' cancer cells will be screened against a panel of chemotherapies and targeted therapies including CAR T cells, to assess the optimal combination of therapies to induce immunotherapy efficacy in otherwise unresponsive CRC.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
Primary hypothesis: Drug screening of patient-derived organoids is a feasible method to identify effective and ineffective therapies for personalized colorectal cancer treatment.
Secondary hypothesis: Pre-treatment with cytotoxic agents can induce cellular immunotherapy efficacy against solid tumors in a colorectal cancer patient-derived organoid model.
Primary objective: To provide methodology and competencies for a clinical trial on drug screening on patient-derived organoids as an approach in personalized cancer treatment.
Secondary objective: To explore induction of cellular immunotherapy efficacy in colorectal cancer patient-derived organoids by chemotherapy or targeted agents.
Study Type
Observational
Enrollment (Estimated)
40
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Sebastian Meltzer, M.D. Ph.D.
- Phone Number: +4767960000
- Email: sebastian.meltzer@medisin.uio.no
Study Locations
-
-
Viken
-
Lørenskog, Viken, Norway, 1478
- Recruiting
- Akershus University Hospital
-
Contact:
- Sebastian Meltzer
- Phone Number: 93608514
- Email: sebastian.meltzer@medisin.uio.no
-
-
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
Sampling Method
Non-Probability Sample
Study Population
Patients with suspected colorectal cancer referred into the program for standardized cancer diagnostic pathways at Akershus University Hospital will be offered enrolment in the study.
Description
Inclusion Criteria:
- Histologically confirmed colorectal cancer scheduled for curative surgery and standard clinical follow-up.
Exclusion Criteria:
- Unable/unwilling to sign the informed consent form.
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
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Primary resectable colon and rectal cancer
Patients with primary resectable, localized colon and rectal cancer eligible for blood and tissue sampling for organoid development.
|
Fresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Clinical logistics pipeline for patient-derived organoid development success rate
Time Frame: March 2022 until March 2023
|
Estimate the feasibility of the implementation of functional diagnostics in a clinical setting. Outcome 1: Inclusion of 10 patients in a study pilot. Measurement 1: Patient inclusion rate per week. Measurement 2: Capacity for organoid development at laboratory facilities (number of patients possible to include per week). Outcome 2: Development of patient-derived organoids from patient tumor samples. Measurement 1: The success rate of organoid development (numbers of organoids developed from the total amount of patients included). |
March 2022 until March 2023
|
|
Sensitivity report for chemotherapy and cellular immunotherapy by clinical evaluation
Time Frame: March 2022 until March 2025
|
Develop drug sensitivity report for clinical use, informing on the functional impact of anti-cancer therapies including cellular therapies ex vivo both by viability assays and real-time imaging analysis.
The drug report will be developed to suit clinical use.
The outcome will be measured in the clinical utility of the drug sensibility report for each patient and to what extent the report can be implemented in clinical practice for further drug selection studies.
Measurement: Assessment of clinical utility by a panel of end-users, including oncologists, surgeons and patient representatives.
|
March 2022 until March 2025
|
|
Induction of immunotherapy efficacy by chemotherapy in colorectal cancer, measured by advanced imaging analysis
Time Frame: May 2022 until March 2025
|
Outcome: Identification of chemotherapy or chemotherapy combinations with or without targeted therapies that induce immunotherapy efficacy in colorectal cancer.
Measurement: By exposing patient-derived organoids to chemotherapy and targeted agents in combination with chimeric antigen receptor (CAR) T cells, the investigators will use advanced imaging and imaging analysis to assess treatment efficacy of the individual therapies and combinations.
|
May 2022 until March 2025
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Sebastian Meltzer, M.D., Ph.D., University Hospital, Akershus
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Veninga V, Voest EE. Tumor organoids: Opportunities and challenges to guide precision medicine. Cancer Cell. 2021 Sep 13;39(9):1190-1201. doi: 10.1016/j.ccell.2021.07.020. Epub 2021 Aug 19.
- Bruun J, Kryeziu K, Eide PW, Moosavi SH, Eilertsen IA, Langerud J, Rosok B, Totland MZ, Brunsell TH, Pellinen T, Saarela J, Bergsland CH, Palmer HG, Brudvik KW, Guren T, Dienstmann R, Guren MG, Nesbakken A, Bjornbeth BA, Sveen A, Lothe RA. Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity. Clin Cancer Res. 2020 Aug 1;26(15):4107-4119. doi: 10.1158/1078-0432.CCR-19-3637. Epub 2020 Apr 16.
- Teijeira A, Migueliz I, Garasa S, Karanikas V, Luri C, Cirella A, Olivera I, Canamero M, Alvarez M, Ochoa MC, Rouzaut A, Rodriguez-Ruiz ME, Sanmamed MF, Klein C, Umana P, Ponz M, Bacac M, Melero I. Three-dimensional colon cancer organoids model the response to CEA-CD3 T-cell engagers. Theranostics. 2022 Jan 1;12(3):1373-1387. doi: 10.7150/thno.63359. eCollection 2022.
- Yong CSM, Dardalhon V, Devaud C, Taylor N, Darcy PK, Kershaw MH. CAR T-cell therapy of solid tumors. Immunol Cell Biol. 2017 Apr;95(4):356-363. doi: 10.1038/icb.2016.128. Epub 2016 Dec 22.
- Caulier B, Enserink JM, Walchli S. Pharmacologic Control of CAR T Cells. Int J Mol Sci. 2021 Apr 21;22(9):4320. doi: 10.3390/ijms22094320.
- Dillard P, Lie M, Baken E, Lobert VH, Benard E, Koksal H, Inderberg EM, Walchli S. Colorectal cysts as a validating tool for CAR therapy. BMC Biotechnol. 2020 Jun 1;20(1):30. doi: 10.1186/s12896-020-00623-0.
- Koksal H, Baken E, Warren DJ, Loset GA, Inderberg EM, Walchli S. Chimeric antigen receptor preparation from hybridoma to T-cell expression. Antib Ther. 2019 May 31;2(2):56-63. doi: 10.1093/abt/tbz007. eCollection 2019 Apr.
- Koksal H, Dillard P, Josefsson SE, Maggadottir SM, Pollmann S, Fane A, Blaker YN, Beiske K, Huse K, Kolstad A, Holte H, Kvalheim G, Smeland EB, Myklebust JH, Inderberg EM, Walchli S. Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma. Blood Adv. 2019 Apr 23;3(8):1230-1243. doi: 10.1182/bloodadvances.2018029678.
- Yang D, Wang X, Zhou X, Zhao J, Yang H, Wang S, Morse MA, Wu J, Yuan Y, Li S, Hobeika A, Lyerly HK, Ren J. Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy. Oncoimmunology. 2021 Sep 27;10(1):1976953. doi: 10.1080/2162402X.2021.1976953. eCollection 2021.
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)
March 28, 2022
Primary Completion (Estimated)
March 28, 2025
Study Completion (Estimated)
January 1, 2027
Study Registration Dates
First Submitted
March 2, 2022
First Submitted That Met QC Criteria
May 28, 2022
First Posted (Actual)
June 2, 2022
Study Record Updates
Last Update Posted (Actual)
August 6, 2024
Last Update Submitted That Met QC Criteria
August 4, 2024
Last Verified
August 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 350208 (REK)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
We do not plan to share individual participant data.
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.