Identification of Novel Biomarkers of Response to Systemic Treatments in Renal Cell Cancer (ARTIST_RCC)

A Retrospective Translational Study to Identify Novel Biomarkers of Response to Systemic Treatments in Renal Cell Cancer

This research study aims to investigate changes inside kidney cancers (also known as Renal Cell Carcinoma or RCC), and in normal kidney surrounding the tumour, when patients are treated with systemic therapy.

Samples, radiological images and data from a previous trial (NeoSUN) will be analysed and/or reanalysed, in accordance with the consent of NeoSUN participants.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Other: Laboratory analysis of samples; Other: Application of machine learning

Detailed Description

This research study aims to investigate changes inside kidney cancers, and in normal kidney surrounding the tumour, when patients are treated with systemic therapy. Systemic treatment is widely used as routine treatment for patients who have kidney cancer that has spread to other organs. It is also used sometimes before surgery to try to shrink kidney cancers to make surgery easier and less risky. Recent research has shown that kidney cancers consist of many different cells in addition to the cancer cells (including immune, structural and blood vessel cells). However, doctors know very little about what changes systemic therapy causes to cells other than cancer cells.

Researchers now think that these other cells may influence how the tumour cells behave during cancer treatment and how well the cancer responds to treatment.

The NeoSUN clinical trial was run at Cambridge University Hospitals between 2006 and 2015.18 patients were treated with a TKI called sunitinib for 12 days before they had their kidney surgically removed. MRI and CT scans were performed before and after the treatment. Samples of tumour and normal kidney were also taken before and after treatment. All patients consented to use of their tissue and data for future research projects. The investigators would like to analyse the effects that sunitinib had on the tumour and other cells using techniques called immunohistochemistry, immunofluorescence, and CyTOF. These mark the different cells so they can easily be identified and the effects on each one analysed. The investigators would also like to re-analyse the scans performed and use artificial intelligence (AI) to see try to detect new trends. The information may help to guide which drugs might be best used in future to treat kidney cancer more effectively whilst keeping side effects low.

• Study Type: Observational
• Enrollment (Anticipated): 12

Contacts and Locations

• Study Contact: Name: Richard Skells; Phone Number: 01223348454; Email: richard.skells@addenbrookes.nhs.uk
• Study Contact Backup: Name: Amanda Walker; Phone Number: 01223256364; Email: amanda.walker@addenbrookes.nhs.uk

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

Participants with renal cell cancer who have given prior consent under NeoSUN for their samples and data to be used, and who have adequate samples and data available.

Description

Inclusion Criteria:

1. Aged 18 years or older
2. Diagnosis of renal cell cancer (any stage).
3. Patient received systemic treatment for their renal cancer at Cambridge University Hospitals NHS Foundation Trust.

4. Patients must have consent in place, for the use of tissue and imaging to be used for the purposes of clinical research;

   • Use of tissue not required for their diagnosis or treatment to be stored and used for the purposes of clinical research, which may include genetic research.
   • Use of relevant sections of their medical records, or by relevant regulatory authorities, where my tissue is being used for research, giving permission for those individuals to have access to their medical records.

5. Participants must also meet at least one of the following criteria to be eligible:

   1. For tissue analysis: Patient must have tumour tissue and/or normal adjacent kidney stored (either as formalinfixed paraffin-embedded tissue, or as 'fresh frozen' tissue).
   2. For imaging analysis: Patient must have had at least 1 scan (either CT or MRI) within 28 days of starting treatment with systemic treatment for their cancer.

Exclusion Criteria:

None

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Research; Patients with Renal Cell Carcinoma who have had previous systemic treatment, with adequate tissue samples and radiological data	Other: Laboratory analysis of samples; RNA sequencing, immunohistochemistry, immunofluorescence, and cytometry of tumour tissues; Other: Application of machine learning; Using machine learning to interrogate data generated from analysis of Renal Cell Cancer tumours using RNA sequencing, immunohistochemistry, immunofluorescence, cytometry, and MRI imaging of tumours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological identification of biomarkers of response to systemic treatment in Renal Cell Cancer.	Using data from RNA sequencing of tumour tissues, the outcome is to identify novel biomarkers of response.	2 years
Radiological identification of biomarkers of response to systemic treatment in Renal Cell Cancer.	Using data from MRI imaging by analysis of the tumour microenvironment and machine learning interrogation of output data, the outcome is to identify novel biomarkers of response.	2 years
Biological identification of biomarkers of response to systemic treatment in Renal Cell Cancer.	Using data from immunohistochemistry, the outcome is to identify novel biomarkers of response.	2 years
Biological identification of biomarkers of response to systemic treatment in Renal Cell Cancer.	Using data from immunofluorescence, the outcome is to identify novel biomarkers of response.	2 years
Biological identification of biomarkers of response to systemic treatment in Renal Cell Cancer.	Using data from CyTOF (mass cytometry), the outcome is to identify novel biomarkers of response.	2 years

Collaborators and Investigators

• Sponsor: CCTU- Cancer Theme
• Investigators: Principal Investigator: Sarah Welsh, Cambridge University Hospitals

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 16, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: August 16, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Cancer; Biomarkers; Renal; Tyrosine Kinase Inhibitors; Systemic Treatments
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: ARTIST RCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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