Tailoring Treatment in Colorectal Cancer

NCT ID: NCT05401318

Last Updated: 2024-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-03-28

Study Completion Date

2027-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colorectal Neoplasms

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Primary resectable colon and rectal cancer

Patients with primary resectable, localized colon and rectal cancer eligible for blood and tissue sampling for organoid development.

Tumor tissue sampling for organoid development

Intervention Type PROCEDURE

Fresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing.

Interventions

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Tumor tissue sampling for organoid development

Fresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing.

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Oncosyne AS

INDUSTRY

Sponsor Role collaborator

Oslo University Hospital

OTHER

Sponsor Role collaborator

University Hospital, Akershus

OTHER

Sponsor Role lead

Responsible Party

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Sebastian Meltzer

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sebastian Meltzer, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Akershus

Locations

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Akershus University Hospital

Lørenskog, Akershus, Norway

Site Status RECRUITING

Countries

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Norway

Central Contacts

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Sebastian Meltzer, M.D. Ph.D.

Role: CONTACT

+4767960000

Facility Contacts

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Sebastian Meltzer

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 34416168 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32299813 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35154495 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28003642 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33919245 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32487146 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33928223 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30979721 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34595059 (View on PubMed)

Other Identifiers

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350208 (REK)

Identifier Type: -

Identifier Source: org_study_id

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