BIO-CHECKPOINT 0 Biomarkers to Identify Oncology Patients on ICPI at Greater Risk of irAE

Characterising Biomarkers and Clinical Algorithms to Identify Oncology Patients on Immune Checkpoint Inhibitors (ICPI) That Are at Greater Risk of Developing Immune-related Adverse Events (irAE)

The study will collect leftover clinic blood samples on new oncology ICPI patients and test them for routine blood tests and malondialdehyde. Malondialdehyde can assess the body's oxidative stress level, a condition where your body lacks antioxidants. The NHS does not offer a malondialdehyde test presently, the study would produce a new NHS blood test. Once testing is completed the samples will be destroyed. Blood test results will be correlated to the patient's outcome i.e., did they have an irAE and assess if there are any differences in the results. From this information, the investigators hope to understand which blood tests help to highlight if a patient is at risk of developing irAE before it occurs.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms

Detailed Description

Immune checkpoint inhibitors (ICPI) are a type of cancer treatment. Unlike traditional chemotherapy and radiation, which damages both the cancer and the healthy tissue, ICPI targets cancer directly by altering the immune system. Cancer cells produce high levels of protein called checkpoint proteins, which bind to white blood cells (which are part of the immune system) and stops them from working. Effectively the cancer is pushing a stop button on the immune system and the body can no longer fight it off. ICPIs block and remove these cancer checkpoint proteins, which allows the immune system to target the cancer again removing this stop button.

ICPI has great success in treating cancer and 10% of oncology NHS patients receive this treatment, although this number is increasing. However, ICPI carries a risk of a type of side effect called immune related adverse events (irAE). irAEs can be life threatening and present with similar symptoms to the patient's cancer. For example, a patient may have kidney cancer and after treatment with ICPI develop kidney failure. It is difficult for the doctor to tell if this is the cancer progressing or a side effect of the treatment. Delays in diagnosing irAE can lead to unnecessary hospitalisation, unnecessary breaks in treatment, lifelong side-effects, and death.

Currently there is not a unified blood test panel for ICPI patients, and the cancer societies have produced little guidance for the doctors to use. At Portsmouth what blood tests you get as an ICPI patient depend on which clinician you see. There is also little research as researchers are focussing on using blood tests to predict ICPI treatment success rather than the chance of a patient developing an irAE.

This study intends to collect leftover blood from routine clinical blood draws from oncology patients being treated with ICPIs for the first time. The investigators will freeze the leftover samples and test them a month later for different routine blood tests as well as malondialdehyde. Malondialdehyde is a blood test that can assess the body's oxidative stress level, a condition where your body lacks antioxidants. Testing for malondialdehyde is not available in the NHS and we would produce a new NHS blood test as part of this study. Once testing is completed the samples will be destroyed as per our normal protocol. At the end of the study, blood test results will be correlated to the patient's outcome i.e., did they have an irAE or not and assess if there are any differences in their blood test results. From this information the study hopes to understand which blood tests help to highlight if a patient is at a risk of developing irAE before it occurs. It also aims to develop a new method for measuring malondialdehyde.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO6 3LY
      • Recruiting
      • Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital
      • Contact: Ian Gedge; Phone Number: 02392286000; Email: research.office@porthosp.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Oncology patients, whom have been prescribed ICPIs for the first time, will be identified via the chemotherapy scheduling system.

Description

Inclusion Criteria:

• ≥18 years of age
• Oncology patients
• Who is prescribed FDA approved check point inhibitors: (ipilimumab, nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, and durvalumab)
• All cancer subtypes are included

Exclusion Criteria:

• <18 years of age
• Those previously been treated with checkpoint inhibitors.
• Those with a previous medical history of autoimmune disease
• Those with previous medical history of endocrine diseases
• Those with a pre-existing malignancy
• Non-Queen Alexandra hospital oncology patients
• Lacking capacity to consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of patient risk of irAE.	A calculation or clinical flow chart that can accurately predict patient's at risk of onset of irAE using routine blood tests and novel biomarkers. Sensitivity, specificity will be calculated and ROC curves.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Significant difference in any established biochemistry, haematology and immunology blood tests in those who develop irAE when compared to those that don't.	Significant difference (p<0.05) in blood test results (concentrations) of those who develop an irAE, opposed to those who don't. Tests include but not limited too: interleukin 6, haptoglobin, C-reactive protein, Beta 2 macroglobin, complement proteins (C3 and C3), lactate dehydrogenase, ferritin, etc.	2 years
Valid liquid chromatograph method fit for clinical laboratory use.	A working liquid chromatograph method fit for use in a clinical laboratory will be developed with working calibration curve and IQC's. With a defined lower limit of blank, lower limit of detection, lower limit of quantification, inter/intra-precision, etc. Calibration curve will aim to have a linearity of R=0.90.	2 years
Significance of Malondialdehyde results.	Malondialdehyde results will be significantly different (p<0.05) in those who develop an irAE opposed to those who do not.	2 years

Collaborators and Investigators

• Sponsor: Portsmouth Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PHU/2023/28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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