Clinical trial NCT06247865: BIO-CHECKPOINT 0 Biomarkers to Identify Oncology Patients on ICPI at Greater Risk of irAE
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neoplasms
Lead sponsor: Portsmouth Hospitals NHS Trust
Sponsor class: OTHER_GOV
First posted: 2024-02-08
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Prediction of patient risk of irAE.
timeFrame: 2 years
Secondary outcomes:
measure: Significant difference in any established biochemistry, haematology and immunology blood tests in those who develop irAE when compared to those that don't.
timeFrame: 2 years
measure: Valid liquid chromatograph method fit for clinical laboratory use.
timeFrame: 2 years
measure: Significance of Malondialdehyde results.
timeFrame: 2 years
Other outcomes:
Locations:
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital
state: Hampshire
Study officials:
References: