Acceptability and Feasibility Study of Patient-specific 'Tumouroids' as Personalised Treatment Screening Tools

Study Overview
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Brief Summary
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In England, more than three hundred thousand people are diagnosed with cancer each year. The diagnostic and treatment pathways for multiple cancers have greatly developed over the past decade. However, novel treatments are expensive and currently discrimination between responders and non-responders is still suboptimal. There is a pressing need to develop tools that allow for better disease characterisation and stratification. Personalised medicine, whereby prevention, diagnosis, and treatment of diseases is aimed at the individual level, is a growing field. Predicting patient-specific treatment response is challenging as response depends not only on the characteristics of cancer cells but also on how these cells interact with their immediate surrounding environment and on how the tumour interacts with the host. A simplistic model is therefore insufficient to predict treatment response. Complex, patient-derived animal models have been used to this effect but are expensive, may take up to 6 months to provide clinically relevant answers, and pose ethical issues. In the past in vitro models lacked complexity as they were based solely on the two-dimensional (2D) growth of cancer cells. Nowadays the use of 3D tumour models has provided an extra level of complexity to in vitro studies. With these models it is possible to recreate tumour characteristics that were lost in 2D, such as cell-cell interaction between cancer cells and between cancer and stromal cells, cell-matrix interaction, or hypoxia. The investigators have developed a 3D complex tumour model - named tumouroid. Using this model, preliminary work has been undertaken which allows the growth of patient-derived tumouroids using primary cancer cells from patients. This personalised platform can be challenged by therapeutics used in clinical practice and response to treatment can be assessed via appropriate assays. The study goals are twofold: To assess patient acceptability to the use of patient derived tumour models for future decision-making, and To assess the feasibility of generating patient derived renal cancer tumouroids and using them as platforms to test drug response.

Detailed Description
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This trial is a prospective tissue collection of renal cell carcinoma samples, including collection of data using both structured Likert 12 item questionnaires and semi structured interviews to assess acceptability. With the development of patient-derived tumouroids the investigators would like to overcome the current over-simplified strategies that focus on genetic markers as predictors of response. In the future, the investigators hope to establish tumouroids as a personalised platform to predict patient response to treatment that is more cost-efficient and poses less ethical issues than animal platforms. This project will assess if patient-derived tumouroids can be therapeutically challenged and if patients would be willing to accept that such platform to guide clinical treatment decision making. This study is designed to assess primarily patient acceptability. Acceptability will be elicited using Likert scale non-validated questionnaires and in a semi-structured interview in which the views and preferences relating the acceptability or otherwise of the patient derived tumour models and their impact on future decision making will be explored. The study will also assess feasibility of building tumouroids and challenging them. Feasibility will address the successful transition between the critical phases of generating a viable and responsive tumour model. This begins with the extraction of cancer cells from the explanted tumour and ends with the determination of a response or otherwise to a therapeutic challenge of the viable tumour model at a range of in vitro concentrations. The findings of this study will be presented at conference(s) and manuscripts will be submitted to appropriate journals for publication.

Official Title
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A Single Site Study Accessing the Acceptability and Feasibility of Patient-specific 'Tumouroids' as Personalised Treatment Screening Tools

Conditions
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Cancer

Intervention / Treatment
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* Other: Questionnaires, interviews and or tissue donation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (≥18 years old), of either gender, able to provide consent; Suspected or confirmed renal cell carcinoma; Signed informed consent by patient Exclusion Criteria: Non-English speaker; Inability to provide informed consent

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 |
| --- | --- |
| Patients with suspected or confirmed renal cell carcinoma<br>Patients with suspected or confirmed renal cell carcinoma who have consented will either donate tissue, or complete a structured questionnaire or a semi-structured interview. Not all patients will have all three interventions, each patient must have at least one. | Other: Questionnaires, interviews and or tissue donation<br>* Subjects will be asked to complete either structured questionnaires, semi-structured interviews or donate tissue. There will be some overlap, but each subject does not have to do all three interventions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability | Measured using a Likert scale non-validated structured questionnaire and/or complete a semi structured interview. | Up to 10 weeks after consent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility : Number of tumour tissue samples collected | Number of tumour tissue samples that can be collected within the time frame from consented patients this will be counted. | Up to 10 weeks after consent | 
| Feasibility : Gross morphology, weight and size of each sample | Each sample obtained will be weighed and measured. | Up to 10 weeks after consent | 
| Feasibility : Cell count after isolation | A physical count of the number of cells isolated from each sample will be collected. | Up to 10 weeks after consent | 
| Feasibility: Cell growth method and time | Measurements will be taken of each tumouroid as it grows, each tumouroid will be given ten days to grow at day ten drug challenge will begin.. | 10 days after tumouroid establishment | 
| Feasibility: Drug concentrations tested | A log will be kept of the drug concentrations used on all tumouroids. | On day 10 after tumouroid establishment | 
| Feasibility: Duration of drug exposure | Number of days tumouroid was exposed to drug | 5 days of drug exposure | 
| Feasibility: Drug challenge response | At the end of 5 days of drug exposure tumouroids will be assessed for response to the drug using a commercially available kit that assesses cell metabolism and viability. In addition, tumouroids will be fixed so that cell morphology will be assessed within 6 days of the end of drug exposure. | within 6 days of the end of drug exposure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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personalised medicine