Tailoring Treatment in Colorectal Cancer

Study Overview
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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.

Official Title
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Pilot Study for Ex Vivo Tailoring of Treatment in Colorectal Cancer

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Procedure: Tumor tissue sampling for organoid development


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Primary resectable colon and rectal cancer<br>Patients with primary resectable, localized colon and rectal cancer eligible for blood and tissue sampling for organoid development. | Procedure: Tumor tissue sampling for organoid development<br>* Fresh tissue from colorectal tumors will be sampled and cultivated in 3D cultures for drug testing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leucovorin, Oxaliplatin, Fluorouracil, Immunotherapy, Colorectal cancer, CAR T-cells, Patient-Derived Organoids