RElugolix VErsus LeUprolide Cardiac Trial (REVELUTION)

Emory University

Status and phase: Active, not recruiting; Phase 4

Conditions: Stage IIIB Prostate Cancer AJCC V8; Stage II Prostate Cancer AJCC V8; Stage IIIA Prostate Cancer AJCC V8; Stage I Prostate Cancer AJCC V8; Localized Prostate Carcinoma; Stage IIA Prostate Cancer AJCC V8; Biochemically Recurrent Prostate Carcinoma; Stage IIC Prostate Cancer AJCC V8; Stage IIIC Prostate Cancer AJCC V8; Stage III Prostate Cancer AJCC V8; Stage IIB Prostate Cancer AJCC V8

Treatments: Drug: Leuprolide; Drug: Relugolix; Radiation: Radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05320406

P30CA138292 (U.S. NIH Grant/Contract)

STUDY00003654

NCI-2022-00117 (Registry Identifier)

22YOUN21 (Other Grant/Funding Number)

RAD5484-21 (Other Identifier)

Details and patient eligibility

About

This phase IV 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.

Full 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.

Enrollment: 93 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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93 participants in 3 patient groups

Arm I (radiation therapy alone)

Active Comparator group

Description:

Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity.

Treatment:

Radiation: Radiation therapy

Arm II (radiation therapy plus leuprolide)

Experimental group

Description:

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.

Treatment:

Radiation: Radiation therapy

Drug: Leuprolide

Arm III (radiation therapy plus relugolix)

Experimental group

Description:

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.

Treatment:

Radiation: Radiation therapy

Drug: Relugolix