Rezvilutamide in Patients With Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of rezvilutamide in combination with androgen deprivation therapy(ADT) and standard salvage radiation therapy(SRT) or rezvilutamide in combination with ADT in prostate cancer patients with biochemical recurrence of prostate-specific antigen(PSA) persistence after radical prostatectomy(RP).

Official Title
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Efficacy and Safety of Rezvilutamide in Patients With Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer: A Prospective, Multi-centre Study

Conditions
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Prostate Cancer, Biochemical Recurrence

Intervention / Treatment
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* Drug: Rezvilutamide
* Drug: Androgen deprivation therapy (ADT)
* Radiation: SRT


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Age ≥ 40 years, male. Patients with histologically-confirmed diagnosis of prostate adenocarcinoma. pathologically node-negative (pN0) or pathologically node cannot be assessed (pNx); Patients with PSA < 0.1ng/ml within 8 weeks after radical prostatectomy (RP) and maintained for at least 6 months; Biochemical recurrence (two consecutive rises in PSA with absolute values > 0.2ng/ml, the time interval ≥ 2 weeks apart ) and no local recurrence or distant metastatic lesions on conventional imaging (bone scan and CT/MRI scan); Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Estimated life expectancy >10 year; Adequate laboratory parameters Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9/L Platelet count (PLT) ≥ 100 x 10^9/L Haemoglobin (Hb) ≥ 90 g/L Serum creatinine (Cr) ≤ 1.5 x upper limit of normal(ULN) or creatinine clearance > 50 ml/min. Total bilirubin (TBIL) ≤ 1.5 x ULN. Glutamic oxaloacetic transaminase (AST/SGOT) or glutamic alanine transaminase (ALT/SGPT) levels ≤ 2.5 x ULN. International normalised ratio (INR) ≤1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT)≤1.5 x ULN . Left ventricular ejection fraction (LVEF) ≥ 50%. Patients able to comply with the protocol. Arm 1 subjects are proposed to receive salvage radiation therapy, while arm 2 subjects are not suitable for or refuse radiation therapy. Signed informed consent. Main Exclusion Criteria: Prior hormonal therapy (antiandrogens or gonadotropin releasing hormone) or prior radiotherapy to pelvic . Postoperative biochemical recurrence with PSA > 2 ng/ml. Postoperative pathology containing neuro-endocrine differentiation or small cell features. Prior malignancy other than prostate cancer in the past three years. History of any of the following: Seizure or known condition that may pre-dispose to seizure Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to entry. Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis) Any other serious or uncontrolled illness which in the opinion of the investigator makes it undesirable for the patient to enter the trial.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rezvilutamide +ADT+ SRT<br>Rezvilutamide along with ADT for 6 cycles (28 days for each cycle) in combination with salvage radiation therapy (SRT) according to standard of care | Drug: Rezvilutamide<br>* Specifications of 80 mg; orally, once a day<br>* Other names: SHR3680;Drug: Androgen deprivation therapy (ADT)<br>* Androgen deprivation therapy (ADT), the ADT used by each subject will be determined by the investigator, and the dose and frequency of administration will be consistent with the prescription information<br>Radiation: SRT<br>* SRT according to standard of care (66.6-72 grays will be delivered to the bed of prostate , 50.4 grays to the pelvis if needed)<br>|
| Experimental: Rezvilutamide +ADT<br>Rezvilutamide along with ADT for 12 cycles (28 days for each cycle) | Drug: Rezvilutamide<br>* Specifications of 80 mg; orally, once a day<br>* Other names: SHR3680;Drug: Androgen deprivation therapy (ADT)<br>* Androgen deprivation therapy (ADT), the ADT used by each subject will be determined by the investigator, and the dose and frequency of administration will be consistent with the prescription information<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year biochemical progression-free survival | For arm 1, biochemical progression is defined as a confirmed prostate specific antigen (PSA) greater than (>) 0.2 nanogram per milliliter (ng/ml) | 24 months | 
| 3-year biochemical progression-free survival | For arm 2, biochemical progression is defined as a confirmed PSA greater than (>) 0.2 ng/ml( the time interval should be over 2 weeks) | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biochemical progression-free survival | Time from entry to biochemical progression or death due to any cause. | 36 months | 
| progression-free survival (PFS) | Time from entry to biochemical progression or radiologically confirmed progressive disease or death due to any cause. | 36 months | 
| metastasis-free survival (MFS) | Time from entry to radiologically confirmed metastasis disease or death due to any cause. | 36 months | 
| Quality of life as determined by FACT-P scores | Quality of life as determined by Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores | At baseline, 3 months, 6 months, every 3 months up to 3 years | 
| Quality of life as determined by EPIC-26 questionnaire | Quality of life as determined by Expanded Prostate Cancer Index Composite-26 (EPIC-26) questionnaire | At baseline, 3 months, 6 months, every 3 months up to 3 years | 
| Number of Adverse Events | Number of Adverse Events | 36 months | 
| Duration of testosterone recovery | Duration of testosterone recovery | 36 months | 
| Time to testosterone recovery to >50 ng/dl | Time to testosterone recovery to >50 ng/dl | 36 months | 
| Time to testosterone recovery to >300 ng/dl | Time to testosterone recovery to >300 ng/dl | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Biochemical recurrence, Rezvilutamide