Colorectal NeoplasmsTargetCRCNCT05401318
Tailoring Treatment in Colorectal Cancer
An observational study of Colorectal Neoplasms, run by University Hospital, Akershus at 1 site in Norway.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Tumor tissue sampling for organoid development
- Type of treatment
- Surgery or procedure
- How many people
- 40 participants
- Where
- 1 siteNorway
- Study dates
- 28 Mar 2022to 1 Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Histologically confirmed colorectal cancer scheduled for curative surgery and standard clinical follow-up.
Who cannot join
- Unable/unwilling to sign the informed consent form.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Norway1 site, 1 recruiting
- Recruiting
Akershus University Hospital
Lørenskog, Akershus, 1478
Sebastian Meltzer, 93608514, sebastian.meltzer@medisin.uio.no
About this study
Official title: 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.
Read the 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.
- Conditions
- Colorectal Neoplasms
- Being tested
- Tumor tissue sampling for organoid development
- Keywords
- Leucovorin, Oxaliplatin, Fluorouracil, Immunotherapy, Colorectal cancer, CAR T-cells, Patient-Derived Organoids
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor tissue sampling for organoid developmentProcedure or surgery
Fresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing.
| Study group | Role | What they receive |
|---|---|---|
| Primary resectable colon and rectal cancer | Patients with primary resectable, localized colon and rectal cancer eligible for blood and tissue sampling for organoid development. Receives: Procedure: Tumor tissue sampling for organoid development |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: March 2022 until March 2023
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.
Measured: March 2022 until March 2025
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.
Measured: May 2022 until March 2025
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2022
- Study start28 Mar 2022
- Primary completion28 Mar 2025 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Collaborators
- Oncosyne AS, Oslo University Hospital
- Responsible party
- Principal investigator, Sebastian Meltzer, University Hospital, Akershus
- Investigators
- Sebastian Meltzer, M.D., Ph.D., Principal investigator, University Hospital, Akershus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05401318
- Sponsor's protocol ID
- 350208 (REK)
- Acronym
- TargetCRC
- Status last verified
- Aug 2024
- First submitted
- 2 Mar 2022
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share individual participant data.
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.
PubMed 34416168Bruun 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.
PubMed 32299813Teijeira 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.
PubMed 35154495Yong 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.
PubMed 28003642Caulier 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.
PubMed 33919245Dillard 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.
PubMed 32487146Koksal 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.
PubMed 33928223Koksal 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.
PubMed 30979721Yang 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.
PubMed 34595059
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study for Ex Vivo Tailoring of Treatment in Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05401318
- Acronym / sponsor ID
- TargetCRC / 350208 (REK)
- Conditions
- Colorectal Neoplasms
- Keywords
- Leucovorin, Oxaliplatin, Fluorouracil, Immunotherapy, Colorectal cancer, CAR T-cells, Patient-Derived Organoids
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Hospital, AkershusUniversity, hospital or other
- Collaborators
- Oncosyne AS, Oslo University Hospital
- Study start
- 28 Mar 2022 (actual)
- Primary completion
- 28 Mar 2025 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 2 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primary resectable colon and rectal cancer | – | Procedure: Tumor tissue sampling for organoid developmentPatients with primary resectable, localized colon and rectal cancer eligible for blood and tissue sampling for organoid development. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- Histologically confirmed colorectal cancer scheduled for curative surgery and standard clinical follow-up.
Key exclusion criteria (1 listed)
- Unable/unwilling to sign the informed consent form.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tumor tissue sampling for organoid developmentFresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing. | Procedure or surgery | Primary resectable colon and rectal cancer |
Primary outcome
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).
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Background: PubMed 34416168Veninga 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.
- Background: PubMed 32299813Bruun 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.
- Background: PubMed 35154495Teijeira 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.
- Background: PubMed 28003642Yong 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.
- Background: PubMed 33919245Caulier 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.
- Background: PubMed 32487146Dillard 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.
- Background: PubMed 33928223Koksal 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.
- Background: PubMed 30979721Koksal 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.
- Background: PubMed 34595059Yang 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.
- Individual participant dataSharing planned: No. We do not plan to share individual participant data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sebastian Meltzer, M.D., Ph.D. principal investigator
University Hospital, Akershus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Neoplasms, run by University Hospital, Akershus at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sebastian Meltzer, M.D. Ph.D. (+4767960000, sebastian.meltzer@medisin.uio.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical logistics pipeline for patient-derived organoid development success rate (time frame: March 2022 until March 2023). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05401318, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.