CV Risk, Prostate Cancer (Diagnosis), Prostate Cancer Stage IV
Conditions
Keywords
High-Risk, Lymph-node positive, ARPI Therapy, CV Risk Factors
Brief summary
In patients with prostate cancer (PC), cardiovascular disease (CVD) causes significant morbidity and is the second leading cause of death. Both pre-existing CVD and the use of androgen deprivation therapy (ADT)-a key cornerstone of treatment for men with locally advanced or metastatic PC1,2 contribute to increased CV risk. ADT has been associated with adverse metabolic effects, including increased central adiposity, elevated low-density lipoprotein (LDL) levels, impaired glycemic control, and arterial wall remodeling and endothelial dysfunction The data demonstrates that for most patients, the status quo is insufficient6 and there remains a critical gap in the early identification of high CV-risk PC patients who may benefit most from aggressive risk mitigation strategies. Mitigation strategies, like the addition of statins as primary prevention, have shown decrease in MI/CHD death across thousands of patients. Age-related expansion of hematopoietic clones carrying recurrent somatic mutations, termed clonal hematopoiesis of indeterminate potential (CHIP) has recently been identified as a significant driver of atherosclerosis, doubling the risk of coronary heart disease. Notably, while CHIP is detectable in \ 10% of persons over 70 years old, it is enriched in patients with solid malignancies, and radiotherapy exposure is among the most decisive risk factors for developing CHIP12-15. The inflammation-related metabolic signals are activated androgen signaling and exacerbated in patients with CHIP. However, the mechanistic link and clinical consequence are less understood. Therefore, it is critical to study the CV impact of CHIP and metabolic perturbations in patients with PC treated with ARSI therapy. We plan to address these critical gaps by testing our innovative hypothesis that early cardio-oncology intervention with aggressive guidelines-based CV optimization during ARPI therapy will reduce CV risk and that CHIP and metabolomics will help identify adverse metabolic remodeling to improve CV risk prediction. Robust epidemiological and clinical trial data consistently demonstrate that patients with PC are poorly optimized from a CV risk modification perspective, and existing CV risk models do not perform well in patients with cancer. The data demonstrates that for most patients, the status quo is insufficient and there remains a critical gap in the early identification of high CV-risk PC patients who may benefit most from aggressive risk mitigation strategies.
Interventions
OTHERCardio-Oncology Referral
Referral to cardio-oncology for guidelines-based personalized cardio-oncology management
OTHERNotification to PCP/General Cardiologist
Notification to patient's primary care physician and/or general cardiologist and recommendation for CV risk optimization after initiation of ARPI therapy
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Following eligibility verification, randomization will occur in REDCap via the Randomization Module. Patients will be randomized in a 1:1 ratio to (A) cardio-oncology management guidelines-based care vs. (B) notification to their primary care physician and/or general cardiologist of ARPI therapy initiation and recommendation for CV risk optimization (control) using stratified block randomization. Refer to section 10.0 for stratification methodology.
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prostate cancer with localized, very-high risk, lymph-node positive, and/or metastatic (Stage IV) disease. * Being treated with ARPI therapy with intended duration ≥ 18 months. * Age \> 65 years old and at least one CV risk factor, or age 45-65 years with at least two CV risk factors: * Hypertension * Hyperlipidemia * Diabetes mellitus * Family history of early CAD (male first-degree relative (father or brother) with CAD before age 55; female first-degree relative (mother or sister) with CAD before age 65) * Presence of coronary artery calcium (CAC) on chest CT imaging * ECOG 0-2 * Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
Exclusion criteria
* Prior ARPI therapy exposure \> 6 months duration. * Established care with cardio-oncologist (cardiologist with expertise in CV risks of cancer and cardiotoxic cancer therapies).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of any CV medication Initiation and/or Change | 3 Months Post-Intervention | To evaluate the rate of any CV medication initiation and/or change at 3-months following cardio-oncology consultation versus standard of care. Rate of any CV medication intervention at 3-months (Note: CV medication defined as: lipid-lowering, anti-hypertensive, anti-anginal, anti-platelet, anti-arrhythmic, heart failure medications) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of Compliance with CV Therapeutic Medication Intervention | 6 and 12 Months Post Intervention | To determine the rate of compliance with CV therapeutic medication intervention at 6 and 12 months |
| Rate of Statin Intervetion | 3 Months Post Intervention | To determine the rate of statin intervention at 3 months |
| Rate of Compliance with Statin Medication Intervention | 6 and 12 Months Post Intervention | To determine the rate of compliance with statin medication intervention at 6 and 12 months |
| Rate of any CV Medication Intervention | 6 Months Post-Intervention | To determine the rate of any CV medication intervention at 6 months |
| Changes in Biological CV Risk Factor | 3, 6, and 12 Month Post-Intervention | To assess changes in biological CV risk factors (low density lipoprotein \[LDL\]) |
| Rate of Coronary Artery Disease Testing | 3, 6, and 12 Month Post-Intervention | To determine the rate of coronary artery disease (CAD) testing (coronary CT angiograms, CAC scans, stress tests, and invasive coronary angiograms) |
| Rate of new CV or Cardiac Diagnosis | 3, 6, and 12 Month Post-Intervention | To determine the rate of new CV or cardiac diagnosis |
| One-Year MACE Rate | 12 Months Post-Intervention | To determine the one-year MACE rate |
| Rate of Grade ≥ 2 Cardiac CTCAE | 12 Month Post-Intervention | To determine one-year rate of grade ≥ 2 cardiac common terminology criteria for adverse events (CTCAE) |
Countries
United States
Contacts
CONTACTClinical Trial Recruitment Navigator
CONTACTKatelyn Atkins, MD, PhD
PRINCIPAL_INVESTIGATORKatelyn Atkins, MD, PhD
Cedars-Sinai Medical Center
PRINCIPAL_INVESTIGATORLeslie Ballas, MD
Cedars-Sinai Medical Center
Outcome results
None listed