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

NCT06597045 | Active Not Recruiting

• 1 other identifier: INGN21CA318
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

cancer; atherosclerosis; FDG; PETCT; cardiotoxicity; VEGFI; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Blood and urine biomarker analysis

  Baseline (pre-treatment) to 24 weeks

• Inflammatory plaque activity (meanMaxTBR) in patients receiving ICI (alone or in combination) vs VEGFI alone.

  Baseline (pre-treatment) to 24 weeks

• PET activity with baseline cardiovascular risk factors and imaging (echo/CT)

  Baseline (pre-treatment) to 24 weeks

• The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined.

  Baseline (pre-treatment) to 24 weeks

• PETCT 18F FDG uptake arterial analyses

  Baseline (pre-treatment) to 24 weeks

Study Arms (3)

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

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

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

Interventions

PET/CT with 18-FDG 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).

Also known as: blood and urine biomarkers, endopat, echocardiography

Immune checkpoint inhibitor / VEGF inhibitor combination therapy; Immune checkpoint inhibitor monotherapy; VEGF inhibitor monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• Roche Diagnostics GmbH: collaborator
• University of Glasgow: collaborator

Study Sites (1)

Beatson West of Scotland Cancer Centre

Glasgow, G120YN, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood and urine biomarkers will be stored.

MeSH Terms

Conditions

Neoplasms; Cardiotoxicity; Atherosclerosis

Interventions

Positron Emission Tomography Computed Tomography; Blood Specimen Collection; Echocardiography

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Positron-Emission Tomography; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography, X-Ray Computed; Multimodal Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cardiac Imaging Techniques; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 19, 2024
• Study Start: August 30, 2022
• Primary Completion: October 14, 2024
• Study Completion: November 20, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

GB (1)