A Multi-center, Randomized, Open-label Clinical Trial Comparing a 6-month vs Long-term Course of Rezvilutamide With ADT Plus Chemotherapy in High Tumor Burden mHSPC
Phase: PHASE3
Conditions: Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Sponsor: The First Affiliated Hospital with Nanjing Medical University

Official title: A Multi-center, Randomized, Open-label Clinical Trial Comparing a 
6-month vs Long-term Course of Rezvilutamide With ADT Plus Chemotherapy in 
High Tumor Burden mHSPC  
 
Date: July 13, 2023 
 
 

Project name 
A Multi-center, Randomized, Open-label Clinical Trial 
Comparing a 6-month vs Long-term Course of Rezvilutamide 
With ADT Plus Chemotherapy in High Tumor Burden 
mHSPC . 
Primary 
Objective: 
 
To explore whether a 6-month course of Rezvilutamide in the 
triple therapy regimen is non-inferior to long-term 
Rezvilutamide treatment in improving radiographic 
progression-free survival (rPFS) in patients with high tumor 
burden metastatic hormone-sensitive prostate cancer (mHSPC). 
 
Secondary Objectives: 
 
To evaluate and compare the time to prostate-specific antigen 
(PSA) progression, time to next bone-related event, time to 
initiation of subsequent anti-prostate cancer treatment, and 
objective response rate (ORR) between the 6-month course of 
Rezvilutamide and long-term androgen deprivation therapy 
(ADT) plus docetaxel treatment in patients with high tumor 
burden mHSPC. 
To assess and compare the incidence of adverse events between 
the 6-month course of Rezvilutamide and long-term ADT plus 
docetaxel treatment in patients with high tumor burden 
mHSPC. 
Exploratory Objectives: 
To observe the circulating tumor cell status at 6 months, 12 
months, 18 months, and 24 months in patients with high tumor 
burden mHSPC receiving the triple therapy regimen. 
Primary Study 
Endpoints: 
 
 
Radiographic progression-free survival (rPFS) 
 
Secondary Study Endpoints: 
 
Time to prostate-specific antigen (PSA) progression 
Time to next bone-related event (including fractures, spinal 
cord compression, radiation therapy, or surgery targeting the 
bones) 
Time to initiation of subsequent anti-prostate cancer treatment 
Objective response rate (ORR) 
Quality of life assessment scores 
Exploratory Study Endpoint: 
 
Circulating tumor cell detection rate 

Study 
Subjects 
Patients with mHSPC have a confirmed pathology of prostate 
adenocarcinoma with high tumor burden, which is defined by 
having at least one of the following conditions: 
 
1) Bone scan showing ≥4 bone metastatic lesions (with at least 
one site outside the pelvis or spine). 
2) CT/MRI revealing visceral metastatic lesions (excluding 
lymph nodes). 
Numbers 
In this study, a total of 100 cases were included. 
Study design 
The study design is a single-center, randomized, positive 
drug-controlled, open-label clinical trial. The subjects were 
randomized and stratified based on the following factors: 
 
1. ECOG performance status (whether greater than 0). 
2. Presence of visceral metastatic lesions (excluding lymph 
nodes). 
Drugs 
Rezvilutamide 
Luteinizing hormone-releasing hormone analogs (LHRHa) 
Docetaxel  
Drugs 
regimen 
Rezvilutamide: 240 mg, once daily, oral administration. 
Luteinizing hormone-releasing hormone analogs (LHRHa): 
Subcutaneous injection, every 1 or 3 months. 
Docetaxel: 75 mg/m2 body surface area, intravenous infusion, 
Day 1, every 21 days for 6 cycles. 
Prednisone: 5 mg, twice daily, oral administration, from Day 1 
to Day 21. 
Patients 
selection 
Inclusion criteria: 
1. Age ≥ 18 years, male. 
2. Eastern Cooperative Oncology Group (ECOG) 
performance status score of 0-1. 
3. Histologically or cytologically confirmed prostate 
adenocarcinoma without evidence of neuroendocrine or 
small cell features. 
4. High tumor burden, defined as having at least one of the 
following conditions: 1) Bone scan showing ≥4 bone 
metastatic lesions (with at least one site outside the 
pelvis or spine). 2) CT/MRI revealing visceral 

metastatic lesions (excluding lymph nodes). 
5. Planned to receive or maintain androgen deprivation 
therapy (ADT) during the study period, either by 
continuous LHRHa treatment or previous bilateral 
orchiectomy (surgical castration), concurrently with 6 
cycles of docetaxel chemotherapy. 
6. Organ function levels must meet the following 
requirements: 
 
Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L. 
 
Platelets (PLT) ≥ 100 × 10^9/L. 
 
Hemoglobin (Hb) ≥ 90 g/L. 
 
Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal 
(ULN). 
 
Alanine aminotransferase (ALT) ≤ 2.5 × ULN. 
 
Aspartate aminotransferase (AST) ≤ 2.5 × ULN. 
 
Blood urea nitrogen (BUN) (or urea) and creatinine (Cr) 
≤ 1.5 × ULN. 
 
Left ventricular ejection fraction (LVEF) ≥ 50%. 
7. Judged by the investigator to be able to comply with the 
trial protocol. 
8. Voluntarily participate in the clinical trial, understand 
the study procedures, and have signed the informed 
consent form. 
 
Exclusion criteria: 
1. Prior treatment with ADT, chemotherapy, surgery, 
external beam radiation therapy, brachytherapy, 
radiopharmaceuticals, or investigational local therapies 
for prostate pain. However, the following cases are 
allowed for inclusion: 
 
Up to 3 months of ADT (medical or surgical 
castration) with or without antiandrogen therapy 

prior to Cycle 1 Day 1 (C1D1) without evidence 
of radiographic disease progression (based on 
RECIST 1.1 criteria) or clinically significant 
PSA rise (defined as ≥50% increase from the 
lowest level after reaching castration levels of 
serum testosterone) before C1D1. 
 
Transurethral prostatectomy or up to one course 
of palliative radiation therapy or surgery for 
symptomatic treatment of metastatic disease at 
least 4 weeks prior to C1D1. All adverse events 
related to these treatments must have improved 
to at least Grade 1 (according to NCI-CTCAE 
v4.03) before starting study treatment. 
2. Prior use or planned use of second-generation androgen 
receptor antagonists (such as enzalutamide, apalutamide, 
darolutamide), abiraterone acetate, or other 
investigational drugs inhibiting testosterone synthesis 
for the treatment of prostate cancer during the study 
period. 
3. Received the following treatments within 4 weeks 
before C1D1: 
 
5-alpha-reductase inhibitors (e.g., finasteride, 
dutasteride). 
 
Estrogens, progestins, androgens, systemic 
corticosteroids (except for temporary use for 
allergic purposes). 
 
Known herbal medicines with anti-prostate 
cancer or PSA-lowering effects (e.g., saw 
palmetto). 
 
Participation in other clinical trials involving 
investigational treatments. 
4. Confirmed brain tumor lesions on imaging. 
5. Planned to receive any other anticancer treatment during 
the trial. 
6. Known allergy or hypersensitivity to apalutamide, ADT, 
or chemotherapy components. 
7. Presence of conditions that impede swallowing, chronic 
diarrhea, intestinal obstruction, or other factors affecting 
drug intake and absorption. 
8. History of seizures or occurrence of conditions that can 
induce seizures within 12 months before C1D1 
(including transient ischemic attack, stroke, traumatic 
brain injury with altered consciousness requiring 
hospitalization). 

9. Presence of active cardiac diseases within 6 months 
before C1D1, including severe/unstable angina, 
myocardial infarction, symptomatic congestive heart 
failure, and ventricular arrhythmias requiring 
medication. 
10. Diagnosis of any other malignancy within 5 years before 
C1D1, except for completely resolved in situ cancer or 
malignancies with slow progression as determined by 
the investigator. 
11. Active HBV or HCV infection (HBV viral load ≥ 
10,000 copies/mL, HCV viral load ≥ 1,000 copies/mL). 
12. History of immunodeficiency (including positive HIV 
test) or organ transplantation. 
13. Unwillingness to use effective contraception during the 
entire study treatment period and for 30 days after the 
last dose. 
14. Judged by the investigator to have conditions that pose a 
serious risk to patient safety, may confound study 
results, or may affect the patient's ability to complete the 
study (such as poorly controlled hypertension, severe 
diabetes, neurological or psychiatric diseases, etc.), or 
any other relevant circumstances. 
 
Criteria of 
abandoning 
the study  
The investigator may decide to discontinue the study drug 
treatment for a participant in the following circumstances: 
1. The participant withdraws informed consent to continue 
receiving the study treatment. 
2. The participant meets the criteria for radiographic 
disease progression in soft tissue and/or bone (as 
determined by each study center based on RECIST 1.1 
and modified PCWG3 criteria, see section 4.3.1). 
3. The participant experiences clinical disease progression 
accompanied by PSA progression (defined in section 
8.1.2). Clinical progression is defined as worsening of 
prostate cancer-related symptoms that the investigator 
deems necessary to treat with any of the following: other 
anticancer treatments, radiation therapy, surgery, or 
intensified analgesic therapy (including the use of new 
opioid analgesics or increasing the dose or frequency of 
existing opioid analgesics). 
4. The participant experiences any clinically significant 
adverse reactions, abnormal laboratory findings, or 
concurrent illnesses that, in the judgment of the 
investigator, make continued participation in the study 

not in the best interest of the participant. 
5. The investigator deems it necessary to withdraw the 
participant from the study due to other reasons, such as 
poor compliance, inability to express a free will due to 
imprisonment or isolation, etc. 
6. The participant dies or is lost to follow-up. 
 
Criteria of 
candidates 
quitting  
The discontinuation of study treatment for a participant does not 
automatically mean their withdrawal from the trial. The 
investigator may decide to withdraw a participant from the 
study in the following circumstances: 
1. The participant withdraws informed consent for the 
collection of subsequent data. 
2. The participant dies or is lost to follow-up. 
3. The sponsor terminates the study. 
 
Criteria of 
termination  
If any of the following situations occur, the trial must be 
terminated: 
1. Major errors are identified in the clinical trial protocol 
that make it difficult to effectively evaluate the drug. 
2. The sponsor requests termination, ensuring the rights 
and safety of the participants. 
3. Regulatory authorities or the ethics committee orders the 
termination of the trial for specific reasons. 
 
Statistical 
approach 
General Analysis: Unless otherwise specified, this study will 
employ the following methods for descriptive statistics. 
Continuous variables will be summarized using mean, standard 
deviation, median, maximum value, and minimum value. 
Categorical variables will be summarized using frequency and 
percentage. Time-to-event data will be analyzed using the 
Kaplan-Meier method to estimate survival rates and median 
survival time. When necessary, corresponding 95% confidence 
intervals will be provided for the aforementioned analyses. 
Efficacy Analysis: The efficacy analysis will involve the 
following methods: 
1. Stratified Log-Rank test: It will be used to compare the 
rPFS (progression-free survival) between groups. The 
Kaplan-Meier method will be utilized to calculate the 
median time to rPFS, along with the two-sided 95% 
confidence interval. Additionally, a stratified Cox 
proportional hazards model will be employed to analyze 
the risk of the experimental group relative to the control 
group. The hazard ratio and its two-sided 95% 

confidence interval will be reported. 
2. Kaplan-Meier method: This will be used to assess the 
time to PSA progression, time to next bone-related 
event, and time to initiation of next anti-prostate cancer 
treatment. Two-sided 95% confidence intervals will be 
provided for these analyses. 
3. Clopper-Pearson method: It will be utilized to estimate 
the 95% confidence interval for the objective response 
rate (ORR). 
Furthermore, the overall analysis will include the summary of 
quality of life scores at various study visit points. 
 
Study period 
3 years