Relugolix in Patients With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy.

Trial details

Who runs it

Istituto Oncologico Veneto IRCCS

Trial code

NCT07927777EU 2025-524702-15-00

Record updated

10 November 2026

Original description

This study is designed to evaluate the efficacy of Relugolix for 3 months before radical prostatectomy + lymph node dissection followed by 6 months Relugolix versus radical prostatectomy + lymphnode dissection followed by 6 months Relugolix. Relugolix is an oral highly selective LHRH antagonist given daily that has been shown to achieve androgen deprivation in both phase I and phase II trials and was finally approved in the phase III HERO trial.Read full original descriptionShow less

A Randomized, Controlled, Phase 3 Study of Relugolix in Patients With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy.

This study is designed to evaluate the efficacy of Relugolix for 3 months before radical prostatectomy + lymph node dissection followed by 6 months Relugolix versus radical prostatectomy + lymphnode dissection followed by 6 months Relugolix. Relugolix is an oral highly selective LHRH antagonist given daily that has been shown to achieve androgen deprivation in both phase I and phase II trials and was finally approved in the phase III HERO trial.

Relugolix is approved in the United States (US) and Europe for the treatment of advanced prostate cancer.

The HERO trial enrolled patients with castration sensitive prostate cancer and compared their sustained castration rate at 48weeks to leuprolide. While the safety profile of the 2 agents was similar, relugolix achieved castrate levels of testosterone faster and provided a higher overall rate of castration. In the phase III HERO trial, relugolix demonstrated suppression of testosterone concentrations to castration levels in 96.7% of patients from Day 29 through 48 weeks, which was superior to leuprolide and resulted in a 54% lower risk of major adverse cardiovascular events. Relugolix also demonstrated superior efficacy to leuprolide for key secondary endpoints, including the cumulative probability of testosterone suppression to castrate levels (< 50 ng/dL) on day 4 and on day 15, PSA response (> 50% decrease) at day 15 with confirmation at day 29, the cumulative probability of testosterone suppression to profound castrate levels (< 20 ng/dL) on day 15, and mean FSH level at the end of week 24. Testosterone recovery was investigated in a subgroup of patients (n = 184): 54% of relugolix recipients versus 3% of leuprolide recipients had testosterone recovery to ≥ 280 ng/dL 90 days after completing 48 weeks of treatment.Relugolix was generally well tolerated in men with prostate cancer, with most adverse events being consistent with physiologic effects of testosterone suppression. Most adverse events were of grade 1 or 2 severity. In a phase II study comparing relugolix to degarelix the global health status, as assessed by EORTC-QLQ-C30, and sexual activity and hormonal treatment-related symptoms, as assessed by the EORTC-QLQ-PR25, were negatively affected during treatment in both groups. Within 12 wk after treatment discontinuation, sexual activity scores improved by a mean of 12.1 for relugolix and 6.6 for degarelix and hormonal treatment-related symptoms changed by a mean of -5.0 and -1, respectively. Similarly, AMS total and subscale scores (sexual, psychological, and somatic) worsened during treatment in both groups but after treatment discontinuation, the mean percentage change in AMS total scores was -15% in the relugolix group and -2.9% in the degarelix group.

The fast testosterone recovery with relugolix was associated with a rapid improvement in a range of castration-related symptoms on QoL measures.

Building upon the practice-changing evidence established by the PROTEUS trial, evaluating oral Relugolix as a perioperative backbone in high-risk patients candidate for radical prostatectomy offers distinct pharmacological, safety, and patient-centered advantages. While PROTEUS validated the clinical benefit of perioperative androgen receptor pathway modulation, Relugolix provides rapid and profound testosterone suppression without an initial surge, paired with a significantly lower cardiovascular risk profile and markedly accelerated post-treatment testosterone and Quality of Life (QoL) recovery compared to standard LHRH agonists. In the HEROIC trial, testing a 3-month neoadjuvant Relugolix induction phase prior to surgery followed by 6 months of adjuvant Relugolix (Arm A) versus immediate surgery followed by 6 months of adjuvant Relugolix (Arm B) addresses whether an all-oral GnRH antagonist strategy can reproduce perioperative oncological downstaging and improve Biochemical Recurrence-Free Survival (bRFS) while optimizing cardiovascular safety and patient recovery.

Inclusion: Male who are at least 18 Years on the day of signing informed consent; Candidate for radical prostatectomy (RP); Adequate organ function (hepatic, renal, hematologic and cerebral) determined at the discretion of the treating physician; Eastern Cooperative oncology Group (ECOG) Performance Status Score of 0 or 1; High risk PCa [biopsy Gleason score 8-10 {ISUP GG 4-5}, PSA >20 ng/ml, cT2c [MRI based], and/or cN1 disease) or non onrgan confined disease defined as cT3-4 and/or cN + [MRI based] any ISUP grade any PSA and were amenable to RP + extended pelvic lymph node dissection (ePLND). A minimun score of Gleason 7(4+3) will be allowed; Staging with PSMA PET/CT (systemic and local) and mpMRI of the prostate and pelvis (as mandatory prebiopsy staging procedure).

Exclusion: Prior or current radiation therapy for treatment of prostate cancer; Received an investigational intervention ≤ 4 weeks before the planned first dose of study intervention; History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect); Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial. There may be exceptions at the discretion of the (coordinating) investigator; Any clinical contraindication to experimental drug adoption as per physician discretion; History of bilateral orchiectomy; Active or symptomatic viral hepatitis or chronic liver disease or HIV; History of pituitary or adrenal dysfunction; Other malignancy; Any condition, which, in the opinion of the investigator, would preclude participation in this trial; Gastrointestinal conditions affecting Absorption; Hypersensitivity to the active substance or to any of the excipients of the study medication; Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the study protocol; Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline; History or presence of soft tissue/bone metastasis or metastasis in distant lymph nodes (pelvic lymph nodes below the iliac bifurcation that are less than (<) 2 centimetres (cm) in diameter [short axis] either radiographically or pathologically are allowed.).

ClinicalTrials.gov NCT07927777 · EU CTIS 2025-524702-15-00