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

Neoplasms Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06247865
• Other study ID #: PHU/2023/28
• Status: Recruiting
• Start date: March 1, 2024
• Est. completion date: May 1, 2025

Study information

• Verified date: April 2024
• Source: Portsmouth Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Locations

Country	Name	City	State
United Kingdom	Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital	Portsmouth	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Portsmouth Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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