Clinical trial NCT05320406: RElugolix VErsus LeUprolide Cardiac Trial
Official title: Mechanism and Predictors of Cardiotoxicity After Prostate Cancer Treatment: A Parallel Cohort and Randomized Trial Comparing Radiation Alone, Radiation Plus Leuprolide, and Radiation Plus Relugolix
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Biochemically Recurrent Prostate Carcinoma
Localized Prostate Carcinoma
Stage I Prostate Cancer AJCC v8
Stage II Prostate Cancer AJCC v8
Stage IIA Prostate Cancer AJCC v8
Stage IIB Prostate Cancer AJCC v8
Stage IIC Prostate Cancer AJCC v8
Stage III Prostate Cancer AJCC v8
Stage IIIA Prostate Cancer AJCC v8
Stage IIIB Prostate Cancer AJCC v8
Stage IIIC Prostate Cancer AJCC v8
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Prostate Cancer Foundation
First posted: 2022-04-11
Enrollment: 94
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical trial investigates the impact of prostate cancer treatment, specifically androgen deprivation therapy (ADT), on the heart and coronary vessels among men with localized, non-metastatic prostate cancer undergoing definitive radiation therapy and concomitant ADT. Recently, cardiovascular toxicity from hormone therapy that is routinely used for prostate cancer (e.g. leuprolide) has emerged as a concern, yet studies identifying who is at risk and the mechanism of cardiac damage are lacking. Additionally, a new hormone therapy drug, relugolix, has recently been Food and Drug Administration (FDA)-approved and may reduce toxicity to the heart. This trial intends to investigate the mechanism of cardiovascular toxicity from ADT, investigate the mechanism by which relugolix reduces cardiovascular toxicity, and identify predictive biomarkers to improve individualized risk-assessment for cardiovascular toxicity from ADT.

Detailed description: PRIMARY OBJECTIVES:

I. Identify and compare the association of gonadotrophin releasing hormone (GNRH)-agonist leuprolide versus GNRH-antagonist relugolix with coronary atherosclerosis and progression in men with prostate cancer.

II. Determine the relationship between leuprolide versus relugolix with downstream immune effector response that is implicated in atherosclerosis.

II. Determine how pre-existing genomic alterations associated with proinflammatory immunity impact development of CV toxicity following GNRH-agonist (GNRHa) versus relugolix.

III. Identify imaging biomarkers associated with increased risk of CV toxicity from ADT

OUTLINE: Patients undergoing radiation therapy alone as part of their standard treatment are assigned to Arm I. Patients undergoing radiation therapy and ADT as part of their standard treatment are randomized to Arm II or Arm III.

ARM I: Patients undergo definitive radiation therapy in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo radiation therapy as in Arm I and receive leuprolide subcutaneously (SC) or intramuscularly (IM) every 3 or 6 months. Treatment continues for 6 to 24 months (depending on cancer risk) in the absence of disease progression or unacceptable toxicity.

ARM III: Patients undergo radiation therapy as in Arm I and receive relugolix orally (PO) once daily (QD) for 6 to 24 months (depending on risk) in the absence of disease progression or unacceptable toxicity.

Eligibility criteria: Inclusion Criteria:

* Men \>= 18 years old
* Non-metastatic prostate cancer
* Non-metastatic, biochemically recurrent prostate cancer
* Plan to undergo curative-intent pelvic radiation therapy with or without ADT

Exclusion Criteria:

* Metastatic prostate cancer requiring \> 24 months of ADT
* Prior exposure to androgen deprivation therapy
* Prior exposure to chemotherapy or immunotherapy
* History of cardiac bypass surgery or percutaneous coronary intervention

Primary outcomes:
measure: Total coronary plaque volume in major coronary arteries (i.e. left anterior descending, left circumflex, right major coronary arteries)
timeFrame: From baseline to 12 months post-treatment initiation
Secondary outcomes:
measure: Non-calcified coronary plaque volume in major coronary arteries (i.e. left anterior descending, left circumflex, right major coronary arteries)
timeFrame: From baseline to 12 months post-treatment initiation
Other outcomes:
measure: Calcified and low-attenuation coronary plaque volume in major coronary arteries (i.e. left anterior descending, left circumflex, right major coronary arteries)
timeFrame: From baseline to 12 months post-treatment initiation
measure: Coronary artery calcium score (CACS)
timeFrame: From baseline to 12 months post-treatment initiation
measure: Coronary vessel stenosis
timeFrame: From baseline to 12 months post-treatment initiation
measure: Major adverse cardiovascular events
timeFrame: From baseline to at least 2 years post-treatment initiation
measure: Testosterone kinetics
timeFrame: Baseline and month 0, 3, 6, 12
Locations:
city: Atlanta
country: United States
facility: Emory Proton Therapy Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: Sagar A Patel, MD
role: PRINCIPAL_INVESTIGATOR
References: