Imaging Technique for Atherosclerosis

Overseen By Clinical Trial Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Katelyn Atkins

Disqualifiers: Low eGFR, Allergy to contrast, Claustrophobia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Thoracic Radiotherapy, HLX-10, HANSIZHUANG, Zerpidio for atherosclerosis?

The research highlights that thoracic radiotherapy, while effective for treating certain cancers, can lead to cardiovascular complications, such as increased arterial stiffness and coronary artery disease, especially in Hodgkin lymphoma survivors. This suggests that while radiotherapy is a powerful cancer treatment, its use in atherosclerosis may require careful consideration of potential heart-related side effects. ^{1 2 3 4 5}

Is the imaging technique for atherosclerosis safe for humans?

Research shows that radiation therapy, which may be similar to the imaging technique you're considering, can increase the risk of heart disease, especially if the heart is exposed to high doses. This risk can manifest many years after treatment, leading to conditions like atherosclerosis (hardening of the arteries) and other heart issues. ^{6 7 8 9 10}

What is the purpose of this trial?

The prospective single-arm pilot study, ATHERO-RT: Real-Time Atherosclerosis Activity after Thoracic Radiotherapy using Sodium Fluoride Positron Emission Tomography, will aim to: 1. To deploy first-in-kind application of fluorine 18-sodium fluoride (18F-NaF) PET (Positron Emission Tomography) /MRI (Magnetic Resonance Imaging) imaging to detect real-time atherosclerosis activity at the time of cancer diagnosis and after cardiac radiation exposure 2. To detect longitudinal changes in clonal hematopoiesis (CH) genetic architecture following thoracic RT (Radiation Therapy) in patients at high risk of cardiac dysfunction, and 3. To measure perturbations in the immune-modulatory and metabolic states following thoracic RT (Radiation Therapy) exposure in patients at high risk of cardiac dysfunction. Eligible patients will be adults (≥18 years old) with Stage II-III or oligo-metastatic stage IV malignancy (any histology) at high risk for RT-associated cardiac toxicity (defined as receiving ≥30 Gy (Gray) RT where the heart is in the treatment field54). The study will enroll a total of 10 subjects, recruited from Cedars-Sinai Medical Center. The primary endpoint will be successful completion of 18F-NaF PET imaging at the baseline and 6-month post-RT time points. Blood will be collected at baseline, end of RT, and 6-months post-RT.

Research Team

Katelyn Atkins, MD, PhD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

This trial is for adults with Stage II-III or oligo-metastatic stage IV cancer, at high risk of heart issues from radiation therapy (RT). They must be receiving RT where the heart is exposed to ≥30 Gy. Only 10 people will be chosen from Cedars-Sinai Medical Center.

Inclusion Criteria

Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

Ability to read, write, and understand English

I am scheduled for standard radiotherapy treatment.

Exclusion Criteria

Allergy to animal dander or animal-instigated asthma

Subjects that are pregnant or breastfeeding

Patients with a known or previous allergy to iodinated contrast, gadolinium contrast, and/or 18F-NaF tracer

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Baseline 18F-NaF PET/MRI imaging to detect real-time atherosclerosis activity at the time of cancer diagnosis

1 week

1 visit (in-person)

Radiation Therapy

Participants receive thoracic radiation therapy with monitoring of cardiac exposure

6-8 weeks

Post-Radiation Imaging

18F-NaF PET/MRI imaging to detect atherosclerosis activity after cardiac radiation exposure

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood collection and assessment of MACE incidence

6 months

2 visits (in-person)

Treatment Details

Interventions

• Thoracic Radiotherapy

Trial Overview The study tests a new imaging technique using PET/MRI scans with Sodium Fluoride to track atherosclerosis activity in real-time during and after RT. It also examines changes in genetic markers and immune/metabolic responses post-RT.

Participant Groups

Group I: Single Arm Experimental Treatment 2 Interventions

Fluorine-18-sodium fluoride (18F-NaF) PET/MRI imaging with CT angiography

Thoracic Radiotherapy is already approved in China, European Union for the following indications:

Approved in China as HANSIZHUANG for:

• Microsatellite instability-high solid tumors
• Squamous non-small cell lung cancer
• Extensive-stage small cell lung cancer
• Esophageal squamous cell carcinoma

Approved in European Union as Hetronifly for:

• Extensive-stage small cell lung cancer

Who Is Running the Clinical Trial?

Katelyn Atkins

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

In a study of 22 patients with esophageal cancer, radiation doses of 20 Gy or higher significantly reduced myocardial blood flow (MBF) in the heart's left ventricle three months after radiation therapy, indicating potential cardiac risks associated with higher radiation exposure.

The findings suggest that monitoring and managing radiation doses during treatment could be crucial in preventing late adverse cardiac events in patients undergoing radiation therapy for thoracic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of reduced myocardial blood flow in the subacute phase after radiation therapy for thoracic esophageal cancer: A quantitative analysis with stress dynamic myocardial computed tomography perfusion imaging. Takada, A., Ichikawa, Y., Nakamura, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Coronary vasomotor dysfunction in cancer survivors treated with thoracic irradiation. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. [2011]

3. United States pubmed.ncbi.nlm.nih.gov

Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Plaque Rupture in a Hodgkin Lymphoma Survivor without Cardiovascular Risk Factors 20 Years after Thoracic Radiotherapy: A Case Report. [2023]

5. France pubmed.ncbi.nlm.nih.gov

[Radiation-related heart toxicity]. [2011]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Coronary Artery Dose-Volume Parameters Predict Risk of Calcification After Radiation Therapy. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Preliminary results of reduced myocardial blood flow in the subacute phase after radiation therapy for thoracic esophageal cancer: A quantitative analysis with stress dynamic myocardial computed tomography perfusion imaging. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Radiotherapy-induced heart disease: a review of the literature. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Experimental radiation-induced heart disease: past, present, and future. [2021]