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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Cardiotoxicity; Atherosclerotic Disease
• Intervention / Treatment: Diagnostic test: PET/CT with 18-FDG

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G120YN
    • Beatson West Of Scotland Cancer Centre

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients attending oncology clinics at the the Beatson West of Scotland Oncology Centre with a diagnosis of cancer and planned for treatment with ICI and/or VEGFi therapies will be screened for entry into the study.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Immune checkpoint inhibitor monotherapy; Patients who are given immune checkpoint inhibitor (ICI) monotherapy (decision on treatment is made by the clinical oncology team. Enrolment to this study had no influence or impact on choice of anti-cancer therapy. Patients were allocated this group if they received at least one cycle of immune check point inhibitor. In the event that a patient is given ICI/VEGFI combination therapy but the VEGFi was stopped early (due to toxicity or lack of clinical effect, determined by the clinical team) and they had less than 50% exposure to VEGFi in the protocol window (24 weeks), the patient will be allocated to ICI monotherapy. Subsequent sensitivity analyses looking at any exposure to VEGFI vs those who had no exposure will be performed.	Diagnostic test: PET/CT with 18-FDG; Study specific tests will include 18F-FDG PET/CT (specialised CT scan), electrocardiography (ECG), clinic blood pressure assessment, blood tests, urine sample, echocardiography (heart ultrasound) and tests on the fingertips (EndoPAT). Positron emission tomography with computerised tomography (PET-CT) is a scanning technique in routine clinical use. It is the gold standard method for assessing blood vessel inflammation. A small amount of radioactive sugar (18F-FDG [18F- fluorodeoxyglucose]) is administered intravenously 90 minutes prior to the PET-CT scan. The distribution of uptake of this tracer is seen on the subsequent PET-CT scan. The CT component of this scan allows the PET image to be precisely aligned with anatomical structures (especially large blood vessels).; Other Names: echocardiography; blood and urine biomarkers; endopat
VEGF inhibitor monotherapy; Patients who are given VEGF inhibitor monotherapy (decision on treatment is made by the clinical oncology team. Enrolment to this study had no influence or impact on choice of anti-cancer therapy Patients will be allocated this group if they are given VEGFi with no exposure to immunotherapy in the study period. If patients are enrolled in the study but stop VEGF inhibitor early they will still be included in this group, provided they do not receive immune checkpoint inhibitor. If during the study protocol window, the patient is exposed to other anti-cancer therapies (other than ICI), in addition to VEGF inhibitor, they will be remain in the VEGFI group.	Diagnostic test: PET/CT with 18-FDG; Study specific tests will include 18F-FDG PET/CT (specialised CT scan), electrocardiography (ECG), clinic blood pressure assessment, blood tests, urine sample, echocardiography (heart ultrasound) and tests on the fingertips (EndoPAT). Positron emission tomography with computerised tomography (PET-CT) is a scanning technique in routine clinical use. It is the gold standard method for assessing blood vessel inflammation. A small amount of radioactive sugar (18F-FDG [18F- fluorodeoxyglucose]) is administered intravenously 90 minutes prior to the PET-CT scan. The distribution of uptake of this tracer is seen on the subsequent PET-CT scan. The CT component of this scan allows the PET image to be precisely aligned with anatomical structures (especially large blood vessels).; Other Names: echocardiography; blood and urine biomarkers; endopat
Immune checkpoint inhibitor / VEGF inhibitor combination therapy; Patients who are given immune checkpoint inhibitor / VEGF inhibitor combination therapy (decision on treatment is made by the clinical oncology team. Enrolment to this study had no influence or impact on choice of anti-cancer therapy). Patients were allocated this group if they received at least one cycle of immune check point inhibitor and VEGFI with more than 50% of the exposure in the study protocol window (24 weeks). Subsequent sensitivity analyses looking at any exposure to VEGFI vs those who had no exposure will be performed.	Diagnostic test: PET/CT with 18-FDG; Study specific tests will include 18F-FDG PET/CT (specialised CT scan), electrocardiography (ECG), clinic blood pressure assessment, blood tests, urine sample, echocardiography (heart ultrasound) and tests on the fingertips (EndoPAT). Positron emission tomography with computerised tomography (PET-CT) is a scanning technique in routine clinical use. It is the gold standard method for assessing blood vessel inflammation. A small amount of radioactive sugar (18F-FDG [18F- fluorodeoxyglucose]) is administered intravenously 90 minutes prior to the PET-CT scan. The distribution of uptake of this tracer is seen on the subsequent PET-CT scan. The CT component of this scan allows the PET image to be precisely aligned with anatomical structures (especially large blood vessels).; Other Names: echocardiography; blood and urine biomarkers; endopat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial TBRmax 18F FDG uptake	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)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood and urine biomarker analysis	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.	Baseline (pre-treatment) to 24 weeks
Inflammatory plaque activity (meanMaxTBR) in patients receiving ICI (alone or in combination) vs VEGFI alone.	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.	Baseline (pre-treatment) to 24 weeks
PET activity with baseline cardiovascular risk factors and imaging (echo/CT)	Correlation between baseline cardiovascular risk factors and imaging (echo/CT) findings will be examined as predictors of subsequent change in inflammatory plaque activity (TBR).	Baseline (pre-treatment) to 24 weeks
The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined.	The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined.	Baseline (pre-treatment) to 24 weeks
PETCT 18F FDG uptake arterial analyses	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.	Baseline (pre-treatment) to 24 weeks

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow; Roche Diagnostics GmbH

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Estimated): October 14, 2024
• Study Completion (Estimated): November 20, 2024

Study Registration Dates

• First Submitted: September 11, 2024
• First Submitted That Met QC Criteria: September 11, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: cancer; atherosclerosis; cardiotoxicity; FDG; immune checkpoint inhibitor; PETCT; VEGFI
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathological Conditions, Anatomical; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiotoxicity; Plaque, Atherosclerotic; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: INGN21CA318

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No