Relugolix in Patients With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy. (HEROIC)
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.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Antonio Amodeo, MD
- 電話番号：0423421321
- メール：antonio.amodeo@iov.veneto.it
研究連絡先のバックアップ
- 名前：Francesco Claps, MD
- 電話番号：0423421321
- メール：francesco.claps@iov.veneto.it
研究場所
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Bologna、イタリア
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico di Sant'Orsola
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コンタクト：
- Riccardo Schiavina
- メール：riccardo.schiavina3@unibo.it
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Milan、イタリア
- Istituto Europeo di Oncologia (IEO)
-
コンタクト：
- Gennaro Musi, MD
- メール：gennaro.musi@ieo.it
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Milan、イタリア
- Humanitas Gavazzeni
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コンタクト：
- Angelo Porreca, MD
- メール：angelo.porreca@hunimed.eu
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Milan、イタリア
- Irccs Humanitas Research Hospital
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コンタクト：
- Buffi Nicolò, MD
- メール：nicolo.buffi@hunimed.eu
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Milan、イタリア
- IRCCS San Raffaele
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コンタクト：
- Alberto Briganti, MD
- メール：briganti.alberto@hsr.it
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Palermo、イタリア
- Fondazione Istituto Giglio - Cefalù
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コンタクト：
- Francesco Curto, MD
- メール：francesco.curto@hsrgiglio.it
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Pisa、イタリア
- Azienda Ospedaliero Universitaria Pisana
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コンタクト：
- Jacopo Durante, MD
- メール：jacopo.durante@ao-pisa.toscana.it
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Ravenna、イタリア
- Ospedale Santa Maria delle Croci - Ravenna
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コンタクト：
- Lorenzo Bianchi, MD
- メール：lorenzo.bianchi3@gmail.com
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Roma、イタリア
- Policlinico Universitario Campus Biomedico Roma
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コンタクト：
- Rocco Papalia, MD
- メール：rocco.papalia@policlinicocampus.it
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Udine、イタリア
- Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) UD
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コンタクト：
- Alessandro Crestani, MD
- 電話番号：0432/552145
- メール：alessandro.crestani@asufc.sanita.fvg.it
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Verona、イタリア
- Azienda Ospedaliera Universitaria Integrata Verona (AOUI VR)
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コンタクト：
- Alessandro Antonelli, Prof
- メール：alessandro.antonelli@aovr.veneto.it
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Italy/Padova
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Padova、Italy/Padova、イタリア、35128
- Istituto Oncologico Veneto
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コンタクト：
- Antonio Amodeo, MD
- 電話番号：0423421321
- メール：antonio.amodeo@iov.veneto.it
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コンタクト：
- Francesco Claps, MD
- 電話番号：0423421321
- メール：francesco.claps@iov.veneto.it
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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 Criteria:
- 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.)
- History of bilateral orchiectomy
- 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)
- Active or symptomatic viral hepatitis or chronic liver disease or HIV
- History of pituitary or adrenal dysfunction
- 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
- 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
- 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Arm A (Experimental)
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). |
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. |
|
アクティブコンパレータ：Arm B (Control)
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). |
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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Biochemical Recurrence-Free Survival (bRFS)
時間枠：Through study completion, an average of 3 years
|
Biochemical Recurrence-Free Survival (bRFS) defined as the time from randomization to the first documented evidence of biochemical recurrence, measured as:
Patients without an event will be censored at the date of their last PSA assessment. |
Through study completion, an average of 3 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Metastasis-Free Survival (MFS)
時間枠：Through study completion, an average of 3 years
|
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. |
Through study completion, an average of 3 years
|
|
Pathological Complete Response (pCR)
時間枠：Through study completion, an average of 3 years
|
pCR will be defined as no residual tumor ypT0 detected in the prostatectomy specimen, as assessed by a pathology BICR); |
Through study completion, an average of 3 years
|
|
Minimal Residual Disease (MRD)
時間枠：Through study completion, an average of 3 years
|
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). |
Through study completion, an average of 3 years
|
|
Overall Survival (OS)
時間枠：Through study completion, an average of 3 years
|
Overall Survival (OS) will be defined as time from randomization to death from any cause |
Through study completion, an average of 3 years
|
|
Time to Castration-Resistant Prostate Cancer (CRPC)
時間枠：Through study completion, an average of 3 years
|
Time to Castration-Resistant Prostate Cancer (CRPC) will be evaluated as time from randomization to evidence of disease progression at CRPC |
Through study completion, an average of 3 years
|
|
Time to First Salvage Therapy (Radiotherapy or systemic)
時間枠：Through study completion, an average of 3 years
|
Time to First Salvage Therapy will be evaluated as time from randomization to the start date of the first systemic therapy or radiotherapy (RT) |
Through study completion, an average of 3 years
|
|
Testosterone suppression and recovery
時間枠：Through study completion, an average of 3 years
|
Testosterone suppression and recovery will be defined as: o Proportion of patients achieving testosterone ≤ 50 ng/dL and ≤ 20 ng/dL during treatment. |
Through study completion, an average of 3 years
|
|
Testosterone suppression and recovery
時間枠：Through study completion, an average of 3 years
|
Testosterone suppression and recovery will be defined as: o Time to testosterone recovery (≥ 280 ng/dL) after treatment discontinuation. |
Through study completion, an average of 3 years
|
|
PSA kinetics
時間枠：Through study completion, an average of 3 years
|
PSA kinetics will be evaluated as proportion of patients achieving ≥ 90% PSA reduction from baseline, and PSA < 0.2 ng/mL at Week 25. |
Through study completion, an average of 3 years
|
|
Quality of Life (QoL)
時間枠：Through study completion, an average of 3 years
|
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 |
Through study completion, an average of 3 years
|
|
Quality of Life (QoL)
時間枠：Through study completion, an average of 3 years
|
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 |
Through study completion, an average of 3 years
|
|
Safety and tolerability of Relugolix
時間枠：Through study completion, an average of 3 years
|
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). |
Through study completion, an average of 3 years
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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