A Phase 3 interventional study of Relugolix-Neoadjuvant treatment and Relugolix-Adjuvant treatment in Locally Advanced Prostate Cancer, sponsored by Istituto Oncologico Veneto IRCCS. Not yet recruiting at 12 sites in Italy. Open to male participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Istituto Oncologico Veneto IRCCS · Phase 3, Interventional, and Treatment
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.
7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.
This study's planned enrollment of 268 is above the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Istituto Oncologico Veneto IRCCS is the lead sponsor of 47 studies on the registry; 13 are open to participants now.
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Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
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Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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Stroke symptoms need emergency care at once, even if they go away.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
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Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
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Investigational drug or device
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It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
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Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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Contraindication
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Relugolix orally (loading dose of 360 mg on Day 1, followed by 120 mg once daily) as neoadjuvant therapy for 3 months prior to radical prostatectomy (RP) with extended pelvic lymphadenectomy (ePLND). Subsequently, post-operative adjuvant treatment with Relugolix for 6 months (loading dose 360 mg, followed by 120 mg/day).
Drug: Relugolix-Neoadjuvant treatment
Immediate undergoing radical prostatectomy (RP) with extended pelvic lymphadenectomy (ePLND), followed by 6 months of post-operative adjuvant treatment with oral Relugolix (loading dose of 360 mg on Day 1, followed by 120 mg once daily).
Drug: Relugolix-Adjuvant treatment
The perioperative treatment will be based on 3 months of Androgen Deprivation Therapy (ADT) with relugolix 120 mg followed by radical prostatectomy (RP) and lymph node dissection. The Relugolix administration will be based on a loading dose of 360 mg, corresponding on 3 tablets, on the first day followed by a 120 mg (one tablet) dose taken once daily at approximately the same time each day. Relugolix can be taken with or without food. Tablets should be taken with some liquid as needed and should be swallowed whole.
Patients allocated on control arm will receive only postoperative treatment. Postoperative treatment will be based on 6 months of relugolix 120 mg after RP. The Relugolix administration will be based on a loading dose of 360 mg, corresponding on 3 tablets, on the first day, followed by a 120 mg (one tablet) dose taken once daily at approximately the same time each day. Relugolix can be taken with or without food. Tablets should be taken with some liquid as needed and should be swallowed whole.
Biochemical Recurrence-Free Survival (bRFS)
Biochemical Recurrence-Free Survival (bRFS) defined as the time from randomization to the first documented evidence of biochemical recurrence, measured as: * A confirmed serum PSA value ≥ 0.2 ng/mL after radical prostatectomy (two consecutive determinations at least 3 weeks apart), or * The clinical decision to initiate salvage therapy (radiotherapy or systemic therapy) for a documented biochemical recurrence (any non-protocol defined treatment) * Any new evidence of metastatic disease on bone or PSMA PET/mpMRI \[imaging modalities as per physician or multidisciplinary team decision's discretion\] * Any local recurrence in the prostate bed, as determined by PSMA PET/ mpMRI; \[imaging modalities as per physician or multidisciplinary team decision's discretion\]. Patients without an event will be censored at the date of their last PSA assessment.
Time frame: Through study completion, an average of 3 years
Metastasis-Free Survival (MFS)
MFS will be defined as the time from randomization to the first radiological evidence of distant metastasis (confirmed by blinded independent central review, BICR) or death from any cause.
Time frame: Through study completion, an average of 3 years
Pathological Complete Response (pCR)
pCR will be defined as no residual tumor ypT0 detected in the prostatectomy specimen, as assessed by a pathology BICR);
Time frame: Through study completion, an average of 3 years
Minimal Residual Disease (MRD)
MRD will be defined as presence of residual tumor ≤ 5 mm in maximal cross-sectional dimension provided it is confined to the prostate, i.e. ypT2 or lower. The primary pathology assessment will be performed by a blinded independent central review (BICR).
Time frame: Through study completion, an average of 3 years
Overall Survival (OS)
Overall Survival (OS) will be defined as time from randomization to death from any cause
Time frame: Through study completion, an average of 3 years
Time to Castration-Resistant Prostate Cancer (CRPC)
Time to Castration-Resistant Prostate Cancer (CRPC) will be evaluated as time from randomization to evidence of disease progression at CRPC
Time frame: Through study completion, an average of 3 years
Time to First Salvage Therapy (Radiotherapy or systemic)
Time to First Salvage Therapy will be evaluated as time from randomization to the start date of the first systemic therapy or radiotherapy (RT)
Time frame: Through study completion, an average of 3 years
Testosterone suppression and recovery
Testosterone suppression and recovery will be defined as: o Proportion of patients achieving testosterone ≤ 50 ng/dL and ≤ 20 ng/dL during treatment.
Time frame: Through study completion, an average of 3 years
Testosterone suppression and recovery
Testosterone suppression and recovery will be defined as: o Time to testosterone recovery (≥ 280 ng/dL) after treatment discontinuation.
Time frame: Through study completion, an average of 3 years
PSA kinetics
PSA kinetics will be evaluated as proportion of patients achieving ≥ 90% PSA reduction from baseline, and PSA \< 0.2 ng/mL at Week 25.
Time frame: Through study completion, an average of 3 years
Quality of Life (QoL)
Quality of Life (QoL) will be assessed by EORTC-QLQ-C30 domain scores at ICF signing, at the end of perioperative period (for Arm A), at 15 days from RP; 4 weeks post-RP; 12 weeks post-RP; End Of Treatment; 12 weeks post-EOT; 6 months post-EOT; 12 months post-EOT
Time frame: Through study completion, an average of 3 years
Quality of Life (QoL)
Quality of Life (QoL) will be assessed by EORTC-QLQ-PR25 domain scores at ICF signing, at the end of perioperative period (for Arm A), at 15 days from RP; 4 weeks post-RP; 12 weeks post-RP; End Of Treatment; 12 weeks post-EOT; 6 months post-EOT; 12 months post-EOT
Time frame: Through study completion, an average of 3 years
Safety and tolerability of Relugolix
Safety and tolerability during the treatment will be recorded and graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE) v.5. Grade refers to the severity of the adverse event. A grading (severity) scale is provided for each adverse event term. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Safety and tolerability will be evaluated also as laboratory, ECG abnormalities and cardiovascular events (MACE).
Time frame: Through study completion, an average of 3 years
Start is estimated for Jan 2027; primary completion for Jan 2030, 36 months later.
Of 139 non-industry phase 3 interventional studies under Prostatic Neoplasms, half reached primary completion within 99 months of starting (the median), counting those still running; a quarter within 57 and three quarters within 144. This study's planned 36 months is below that.
Counting every sponsor, half of 265 studies reached it within 57 months; a quarter within 31 and three quarters within 100.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.
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Istituto Oncologico Veneto IRCCS