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| Name | Class |
|---|---|
| Roche Diagnostics GmbH | INDUSTRY |
| University of Glasgow | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beatson West of Scotland Cancer Centre | Glasgow | G120YN | United Kingdom |
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blood and urine biomarkers will be stored.
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| 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 |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D066126 | Cardiotoxicity |
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000072078 | Positron Emission Tomography Computed Tomography |
| D001800 | Blood Specimen Collection |
| D004452 | Echocardiography |
| ID | Term |
|---|---|
| D049268 | Positron-Emission Tomography |
| D014055 | Tomography, Emission-Computed |
| D007090 | Image Interpretation, Computer-Assisted |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D014057 | Tomography, X-Ray Computed |
| D064847 | Multimodal Imaging |
| D011856 | Radiographic Image Enhancement |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011859 | Radiography |
| D014056 | Tomography, X-Ray |
| D011877 | Radionuclide Imaging |
| D014054 | Tomography |
| D003947 | Diagnostic Techniques, Radioisotope |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D057791 | Cardiac Imaging Techniques |
| D014463 | Ultrasonography |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
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