BIOMARKER and IMAGING CHARACTERISATION of INFLAMMATORY ATHEROMA in PATIENTS RECEIVING IMMUNOTHERAPY and ANGIOGENESIS INHIBITORS

Active, not recruiting

• Conditions: Cancer; Cardiotoxicity; Atherosclerotic Disease

• Registration Number: NCT06597045
• Lead Sponsor: NHS Greater Glasgow and Clyde

Brief Summary

The advent of immunotherapy (immune checkpoint inhibitors \[ICI\]) has been an extremely important advancement for cancer treatment in recent decades. The anti-cancer effects of these agents is profound and can lead to radiological \'disappearance\' of the primary cancer and metastatic deposits. ICI are now commonly used in the treatment of multiple cancers including melanoma, kidney cancer, liver cancer and lung cancer. ICI can be used on their own or in combination with other agents such as vascular endothelial growth factor inhibitors (VEGFi) which is first line treatment for many patients. However, it has become clear that these drugs have cardiovascular side effects including high blood pressure and a reduction in the heart muscle pumping function. It is also increasingly recognised that ICIs may have a toxic effect on blood vessels resulting in an increased risk of heart attack or stroke. These side effects can have a significant impact on patients\' health and can lead to withdrawal of important cancer treatment. The mechanisms by which these side effects occur are unclear and have not been well described to date.

The aim of this study is to examine the effect of ICI and VEGFi, both alone and in combination, on blood vessels and to understand their effects on blood markers and heart function. This study is observational and will not require any modification of cancer therapy.

This study will aim to recruit patients diagnosed with cancer who are already planned to receive ICI or VEGFi alone or in combination at the Beatson West of Scotland Oncology Centre. Patients will undergo a vascular PET-CT scan before and 6 months after starting treatment. In addition patients will undergo echocardiography and tests of the function of the small blood vessels in the fingertips with a special machine (EndoPat). Blood and urine samples will also be collected.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-30
• Status Verified: 2024-09
• Study First Submitted: 2024-09-11
• Study First Submitted QC: 2024-09-11
• Last Update Submitted: 2024-09-11
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19
• Primary Completion: 2024-10-14
• Study Completion: 2024-11-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Patients with cancer who are planned for treatment with ICI or VEGFI, including combination therapy
2. ≥6 months predicted survival
3. Age ≥18 years

Exclusion Criteria

1. Patients who are unable or unwilling to provide valid consent for the study
2. Patients with diabetes who are on oral anti-diabetic treatment or insulin at baseline
3. patients who have exposure to either immune checkpoint inhibitor or VEGF inhibitor in the 12 months before enrolment

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mean arterial TBRmax 18F FDG uptake	24 weeks	Inflammatory plaque activity (meanMaxTBR)\* in patients receiving ICI/VEGFI combination therapy versus ICI alone or VEGFI alone.; \*Note \'meanMaxTBR\' is a PET measurement reflecting the average of the maximum \'target to background ratio \[TBR\]) where \'target\' denotes regions of PET radiotracer activity)

Secondary Outcome Measures

Name	Time	Method
Blood and urine biomarker analysis	Baseline (pre-treatment) to 24 weeks	Correlation between baseline and longitudinal changes in humoral/urinary biomarkers as potential predictors of subsequent change in inflammatory plaque activity (TBR).; Analysis of blood and urine biomarkers with inflammatory plaque activity (meanMaxTBR) in patients receiving ICI (alone or in combination) vs VEGFI alone.
Inflammatory plaque activity (meanMaxTBR) in patients receiving ICI (alone or in combination) vs VEGFI alone.	Baseline (pre-treatment) to 24 weeks	In addition to ICI vs VEGFI vs ICI/VEGFI combination therapy, we will also compare PET activity in those who had ICI (monotherapy or combination therapy) with VEGFi monotherapy.
PET activity with baseline cardiovascular risk factors and imaging (echo/CT)	Baseline (pre-treatment) to 24 weeks	Correlation between baseline cardiovascular risk factors and imaging (echo/CT) findings will be examined as predictors of subsequent change in inflammatory plaque activity (TBR).
The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined.	Baseline (pre-treatment) to 24 weeks	The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined.
PETCT 18F FDG uptake arterial analyses	Baseline (pre-treatment) to 24 weeks	In accordance with European Association of Nuclear Medicine guidelines, in addition to TBRmax, arteries will be analysed using TBRmean (tissue to background ratio mean FDG uptake), active segment; and most diseased segment.

Trial Locations

Locations (1)

Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom