High Cardiovascular Risk Intervention With Cardio-Oncology Consultation for Prostate Cancer Following Androgen Receptor Pathway Inhibitor (ARPI) Therapy (Heart-Safe)

NCT07223385 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT2025-09-BALLAS-ATKINS-HEART
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer (Diagnosis); CV Risk; Prostate Cancer Stage IV

Keywords

High-Risk; Lymph-node positive; ARPI Therapy; CV Risk Factors

Outcome Measures

Primary Outcomes (1)

• Rate of any CV medication Initiation and/or Change

  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)

  3 Months Post-Intervention

Secondary Outcomes (12)

• The Rate of Compliance with CV Therapeutic Medication Intervention

  6 and 12 Months Post Intervention

• Rate of Statin Intervetion

  3 Months Post Intervention

• Rate of Compliance with Statin Medication Intervention

  6 and 12 Months Post Intervention

• Rate of any CV Medication Intervention

  6 Months Post-Intervention

• Changes in Biological CV Risk Factor

  3, 6, and 12 Month Post-Intervention

Study Arms (2)

Cardo-Oncolody Referral

EXPERIMENTAL

Referral to cardio-oncology for guidelines-based personalized cardio-oncology management

Other: Cardio-Oncology Referral

PCP/General Cardiology Care

ACTIVE COMPARATOR

Notification to patient's primary care physician and/or general cardiologist and recommendation for CV risk optimization after initiation of ARPI therapy

Other: Notification to PCP/General Cardiologist

Interventions

Cardio-Oncology Referral OTHER

Referral to cardio-oncology for guidelines-based personalized cardio-oncology management

Cardo-Oncolody Referral

Notification to PCP/General Cardiologist OTHER

Notification to patient's primary care physician and/or general cardiologist and recommendation for CV risk optimization after initiation of ARPI therapy

PCP/General Cardiology Care

Eligibility Criteria

• Age: 45 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior ARPI therapy exposure \> 6 months duration.
• Established care with cardio-oncologist (cardiologist with expertise in CV risks of cancer and cardiotoxic cancer therapies).

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Disease

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Katelyn Atkins, MD, PhD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

• Leslie Ballas, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Recruitment Navigator

CONTACT

13104232133; GroupCancerTrialInformation@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: 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.

Study Record Dates

• First Submitted: October 29, 2025
• First Posted: October 31, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)