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

NCT ID: NCT06597045

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-08-30
• Study Completion Date: 2024-11-20

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.

Conditions

Cancer; Cardiotoxicity; Atherosclerotic Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

PET/CT with 18-FDG

Intervention Type: DIAGNOSTIC_TEST

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).

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.

PET/CT with 18-FDG

Intervention Type: DIAGNOSTIC_TEST

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).

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.

PET/CT with 18-FDG

Intervention Type: DIAGNOSTIC_TEST

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).

Interventions

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).

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

blood and urine biomarkers; endopat; echocardiography

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Diagnostics GmbH

INDUSTRY

Sponsor Role: collaborator

University of Glasgow

OTHER

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Countries

United Kingdom

Other Identifiers

INGN21CA318

Identifier Type: -

Identifier Source: org_study_id