Tailoring Treatment in Colorectal Cancer

Colorectal Neoplasms Clinical Trial

— TargetCRC  

Official title:

Pilot Study for Ex Vivo Tailoring of Treatment in Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05401318
• Other study ID #: 350208 (REK)
• Status: Recruiting
• Start date: March 28, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: March 2023
• Source: University Hospital, Akershus
• Contact: Sebastian Meltzer, M.D. Ph.D.
• Phone: +4767960000
• Email: sebastian.meltzer[@]medisin.uio.no
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 1, 2027
• Est. primary completion date: March 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Procedure:
• Tumor tissue sampling for organoid development
Fresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing.

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lørenskog	Viken

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Akershus	Oncosyne AS, Oslo University Hospital

Country where clinical trial is conducted

Norway, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical logistics pipeline for patient-derived organoid development success rate	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
Primary	Sensitivity report for chemotherapy and cellular immunotherapy by clinical evaluation	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
Primary	Induction of immunotherapy efficacy by chemotherapy in colorectal cancer, measured by advanced imaging analysis	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