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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2022-00117 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| STUDY00003654 | |||
| RAD5484-21 | Other Identifier | Emory University Hospital/Winship Cancer Institute | |
| P30CA138292 | U.S. NIH Grant/Contract | View source | |
| 22YOUN21 | Other Grant/Funding Number | Prostate Cancer foundation |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Prostate Cancer Foundation | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (radiation therapy alone) | Active Comparator | Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity. |
|
| Arm II (radiation therapy plus leuprolide) | Experimental | Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. |
|
| Arm III (radiation therapy plus relugolix) | Experimental | Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiation therapy | Radiation | Undergo radiation therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries) | Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments. | From baseline to 12 months post-treatment initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Non-calcified Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries) | Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments. |
| Measure | Description | Time Frame |
|---|---|---|
| Calcified and Low-attenuation Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries) | Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sagar A Patel, MD | Emory University Hospital/Winship Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory Proton Therapy Center | Atlanta | Georgia | 30308 | United States | ||
| Emory University Hospital Midtown |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41706486 | Derived | Patel SA, Yadalam AK, van Assen M, Cantu SM, Onnis C, Zheng B, Koo A, Goyal S, Liu Y, Liu C, Sebastian NT, Dhere VR, Hershatter BW, Patel PR, Chaudagar K, Stillman AE, De Cecco CN, Sanda MG, Jani AB, Mandawat A. Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate Cancer: A Randomized Clinical Trial. JAMA Cardiol. 2026 May 1;11(5):459-463. doi: 10.1001/jamacardio.2025.5586. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I (Radiation Therapy Alone) | Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy |
| FG001 | Arm II (Radiation Therapy Plus Leuprolide) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 5, 2024 |
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|
| Leuprolide | Drug | Given IM or SC |
|
|
| Relugolix | Drug | Given PO |
|
|
| From baseline to 12 months post-treatment initiation |
| From baseline to 12 months post-treatment initiation |
| Coronary Artery Calcium Score (CACS) | The CACS will be measured by the Agatston score (range 0-400, with higher scores indicating more coronary artery calcium) on precontrast cardiac computed tomography anigiography (CCTA) scans by two blinded, board-certified cardiologists. | From baseline to 12 months post-treatment initiation |
| Number of Participants With <30%, 30-49%, 50-69%, and >70% Maximum Coronary Vessel Stenosis at Baseline and Month 12 | Coronary computed tomographic angiography post-contrast images were used for vessel stenosis, using an artificial intelligence-informed coronary stenosis quantification tool (AI-CSQ, Roadmap Analysis, Heart flow, Mountain View CA). Stenoses regions are defined in ranges of 0-29%, 30-49%, 50-69%, and >70%. The number of participants within each treatment meeting these stenosis thresholds were quantified at baseline and month 12. | From baseline to 12 months post-treatment initiation |
| Major Adverse Cardiovascular Events | Incidence of myocardial infarction, need for coronary revascularization, and/or sudden cardiac death will be measured for up to 2 years following enrollment. | From baseline to at least 2 years post-treatment initiation |
| Testosterone Kinetics | Change in total testosterone levels (ng/dL) will be measured at baseline and month 0, 3, 6, and 12 between treatment arms. Testosterone change over time will be summarized and plotted over time for each treatment arm. | Baseline and month 0, 3, 6, 12 |
| Atlanta |
| Georgia |
| 30308 |
| United States |
| Emory University/Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
| Emory Saint Joseph's Hospital | Atlanta | Georgia | 30342 | United States |
Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Leuprolide: Given IM or SC |
| FG002 | Arm III (Radiation Therapy Plus Relugolix) | Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Relugolix: Given PO |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm I (Radiation Therapy Alone) | Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy |
| BG001 | Arm II (Radiation Therapy Plus Leuprolide) | Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Leuprolide: Given IM or SC |
| BG002 | Arm III (Radiation Therapy Plus Relugolix) | Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Relugolix: Given PO |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries) | Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments. | Posted | Median | 95% Confidence Interval | mm3 | From baseline to 12 months post-treatment initiation |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Non-calcified Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries) | Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments. | Posted | Median | 95% Confidence Interval | mm3 | From baseline to 12 months post-treatment initiation |
| |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Calcified and Low-attenuation Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries) | Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments. | Posted | Median | 95% Confidence Interval | mm3 | From baseline to 12 months post-treatment initiation |
| |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Coronary Artery Calcium Score (CACS) | The CACS will be measured by the Agatston score (range 0-400, with higher scores indicating more coronary artery calcium) on precontrast cardiac computed tomography anigiography (CCTA) scans by two blinded, board-certified cardiologists. | Posted | Median | 95% Confidence Interval | Agatston score (range 0-400) | From baseline to 12 months post-treatment initiation |
| |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With <30%, 30-49%, 50-69%, and >70% Maximum Coronary Vessel Stenosis at Baseline and Month 12 | Coronary computed tomographic angiography post-contrast images were used for vessel stenosis, using an artificial intelligence-informed coronary stenosis quantification tool (AI-CSQ, Roadmap Analysis, Heart flow, Mountain View CA). Stenoses regions are defined in ranges of 0-29%, 30-49%, 50-69%, and >70%. The number of participants within each treatment meeting these stenosis thresholds were quantified at baseline and month 12. | Posted | Count of Participants | Participants | From baseline to 12 months post-treatment initiation |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Major Adverse Cardiovascular Events | Incidence of myocardial infarction, need for coronary revascularization, and/or sudden cardiac death will be measured for up to 2 years following enrollment. | Posted | Count of Participants | Participants | From baseline to at least 2 years post-treatment initiation |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Testosterone Kinetics | Change in total testosterone levels (ng/dL) will be measured at baseline and month 0, 3, 6, and 12 between treatment arms. Testosterone change over time will be summarized and plotted over time for each treatment arm. | Posted | Mean | Standard Error | ng/mL | Baseline and month 0, 3, 6, 12 |
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm I (Radiation Therapy Alone) | Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy | 0 | 28 | 0 | 28 | 23 | 28 |
| EG001 | Arm II (Radiation Therapy Plus Leuprolide) | Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Leuprolide: Given IM or SC | 1 | 31 | 1 | 31 | 27 | 31 |
| EG002 | Arm III (Radiation Therapy Plus Relugolix) | Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Relugolix: Given PO | 0 | 31 | 0 | 31 | 30 | 31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| sepsis | Infections and infestations | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cystitis noninfective | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Fatigue | General disorders | Non-systematic Assessment |
| ||
| Hot flashes | Vascular disorders | Non-systematic Assessment |
| ||
| Urinary frequency | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Urinary retention | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Urinary urgency | Renal and urinary disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sagar Patel | Emory University | 404-778-1900 | sagar.patel@emory.edu |
| Sep 23, 2025 |
| Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 19, 2025 | May 9, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D050397 | Radiotherapy, Intensity-Modulated |
| D061766 | Proton Therapy |
| D001918 | Brachytherapy |
| D016634 | Radiosurgery |
| D016729 | Leuprolide |
| C561634 | relugolix |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D020266 | Radiotherapy, Conformal |
| D011881 | Radiotherapy, Computer-Assisted |
| D063193 | Heavy Ion Radiotherapy |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Relugolix: Given PO |
|
|
Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Relugolix: Given PO |
|
|
|
|
Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity. Radiation therapy: Undergo radiation therapy Relugolix: Given PO |
|
|
|
|
|
|
| 50% - 69% |
|
| 70% - 99% |
|