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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Other: Questionnaires, interviews and or tissue donation

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 19

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, NW12BX
    • Surgical & Interventional Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male or female patients aged 18 or over, sufficient command of English language to complete consent forms and questionnaires, suspected or confirmed renal cell carcinoma.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with suspected or confirmed renal cell carcinoma; 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; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Mark Emberton, Professor of Interventional Oncology, UCL

Publications and helpful links

General Publications

• Tran MGB, Neves JB, Stamati K, Redondo P, Cope A, Brew-Graves C, Williams NR, Grierson J, Cheema U, Loizidou M, Emberton M. Acceptability and feasibility study of patient-specific 'tumouroids' as personalised treatment screening tools: Protocol for prospective tissue and data collection of participants with confirmed or suspected renal cell carcinoma. Int J Surg Protoc. 2019 Apr 2;14:24-29. doi: 10.1016/j.isjp.2019.03.019. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): January 24, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: personalised medicine
• Other Study ID Numbers: 17/0351

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No