A Multicenter, Prospective, Randomized Controlled Phase II Clinical Trial of Prostatectomy After Conversion Therapy With Second-generation Antiandrogen Agents Plus ADT in Patients With High-volume mHSPC(CONVERT-HB1)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Radiographic Progression-free Survival (rPFS)
研究概览
简要总结
This is a prospective, randomized, open-label, phase II multicenter clinical trial evaluating the efficacy and safety of radical prostatectomy in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve good response after systemic therapy with androgen deprivation therapy (ADT) plus second-generation antiandrogens such as rezvilutamide. All eligible patients will receive 6 months of induction systemic therapy (ADT plus second-generation androgen receptor signaling inhibitors, with or without docetaxel or other systemic agents). Patients who achieve PSMA PET/CT "conversion success" (no metabolically active lesions; all metastases with SUVmax below liver background or blood pool) will be randomized 1:1 to continue systemic therapy alone (control arm) or receive local prostate treatment (radical prostatectomy or radiotherapy) plus systemic therapy (experimental arm). The primary endpoint is radiographic progression-free survival (rPFS). Key secondary endpoints include overall survival (OS), biochemical progression-free survival (bPFS), PSA response rate, quality of life, conversion success rate, and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients aged >18 and ≤70 years, or with an estimated life expectancy >10 years.
- •Histologically or cytologically confirmed prostate adenocarcinoma with neuroendocrine differentiation ≤10%, and no small cell or signet-ring cell carcinoma component.
- •High-volume metastatic disease according to CHAARTED definition: presence of visceral metastasis and/or ≥4 bone lesions with at least one lesion outside the axial skeleton (vertebral bodies and pelvis).
- •Newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) who started intensified endocrine therapy within 3 months.
- •ECOG performance status 0-
- •Adequate bone marrow, liver, renal, and coagulation function as defined in the protocol (ANC ≥1.5×10^9/L, hemoglobin ≥9.0 g/dL, platelets ≥80×10^9/L; TBIL ≤1.5×ULN; AST/ALT/ALP ≤2.5×ULN; albumin ≥30 g/L; creatinine ≤2×ULN or creatinine clearance ≥30 mL/min; INR ≤1.5 in patients not receiving anticoagulation).
- •Patients voluntarily sign informed consent and are willing and able to comply with study procedures.
排除标准
- •History of hypersensitivity or intolerance to any study drugs.
- •mCRPC (metastatic castration-resistant prostate cancer).
- •Oligometastatic mHSPC intended for upfront radical prostatectomy.
- •History of seizure, medications that may lower seizure threshold, or conditions predisposing to seizures (e.g., TIA, stroke, significant head trauma with loss of consciousness requiring hospitalization) within 12 months before starting study treatment.
- •Major surgery within 4 weeks prior to starting study treatment.
- •Significant cardiovascular or cerebrovascular disease within 6 months (e.g., unstable angina, myocardial infarction, NYHA class III or higher heart failure, stroke, clinically significant arrhythmia requiring treatment).
- •Conditions affecting drug intake or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction).
- •Active infection (e.g., HIV positive, HBsAg positive, HCV positive) which in the investigator's opinion may affect safety or efficacy assessment.
- •Other malignancies within the past 3 years, except adequately treated basal cell carcinoma of the skin.
- •Known brain metastases or leptomeningeal disease.
- •Concurrent participation in another interventional clinical trial or receiving other investigational drugs/devices.
- •Poor compliance or inability to adhere to study procedures and follow-up.
- •Any other severe uncontrolled comorbidities (e.g., poorly controlled hypertension, severe diabetes, neurologic or psychiatric disorders) or conditions that may interfere with study conduct or interpretation, as judged by the investigator.
研究组 & 干预措施
Systemic Therapy Alone
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm A will continue standard systemic therapy alone without local prostate surgery or radiotherapy. Systemic therapy consists of androgen deprivation therapy (ADT) using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), admini
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Systemic Therapy Alone
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm A will continue standard systemic therapy alone without local prostate surgery or radiotherapy. Systemic therapy consists of androgen deprivation therapy (ADT) using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), admini
干预措施: Docetaxel (Drug)
Systemic Therapy Alone
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm A will continue standard systemic therapy alone without local prostate surgery or radiotherapy. Systemic therapy consists of androgen deprivation therapy (ADT) using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), admini
干预措施: PARP Inhibitors and Other Systemic Agents (Drug)
Systemic Therapy Plus Local Prostate Treatment (Arm B)
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm B will receive local prostate treatment in addition to continued standard systemic therapy. Systemic therapy consists of ADT using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), administered according to approved labels
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Systemic Therapy Plus Local Prostate Treatment (Arm B)
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm B will receive local prostate treatment in addition to continued standard systemic therapy. Systemic therapy consists of ADT using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), administered according to approved labels
干预措施: Docetaxel (Drug)
Systemic Therapy Plus Local Prostate Treatment (Arm B)
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm B will receive local prostate treatment in addition to continued standard systemic therapy. Systemic therapy consists of ADT using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), administered according to approved labels
干预措施: PARP Inhibitors and Other Systemic Agents (Drug)
Systemic Therapy Plus Local Prostate Treatment (Arm B)
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm B will receive local prostate treatment in addition to continued standard systemic therapy. Systemic therapy consists of ADT using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), administered according to approved labels
干预措施: Radical Prostatectomy (Procedure)
Systemic Therapy Plus Local Prostate Treatment (Arm B)
Participants with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve "conversion success" after induction systemic therapy will be randomized to this arm at either the 6-month or 12-month evaluation. Conversion success is defined based on PSMA PET/CT as all metastatic lesions showing no obvious uptake (SUVmax lower than liver SUVmean or blood pool SUVmean) and fulfilling all predefined clinical and radiological criteria for randomization.
Patients randomized to Arm B will receive local prostate treatment in addition to continued standard systemic therapy. Systemic therapy consists of ADT using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) combined with second-generation androgen receptor signaling inhibitors (such as rezvilutamide, enzalutamide, apalutamide, darolutamide, or abiraterone), with or without docetaxel and other systemic agents (e.g., PARP inhibitors such as olaparib), administered according to approved labels
干预措施: Prostate Radiotherapy (Radiation)
结局指标
主要结局
Radiographic Progression-free Survival (rPFS)
时间窗: From randomization to radiographic progression or death from any cause, whichever occurs first, up to approximately 24 months.
rPFS will be assessed according to RECIST v1.1 and PCWG3 criteria using PSMA PET/CT, contrast-enhanced CT, MRI, or bone scan. Radiographic progression is defined as the appearance of new lesions or growth of existing measurable disease as per RECIST v1.1, or new bone lesions according to the PCWG3 "2+2" rule
次要结局
- Overall Survival (OS)(From start of systemic therapy to death from any cause, up to the end of follow-up (approximately 24-30 months).)
- Biochemical Progression-free Survival (bPFS)(From start of systemic therapy to biochemical progression or death, up to ~24 months.)
- PSA Response Rate at 3 and 6 Months(3 months and 6 months after treatment)
- Conversion Success Rate(At 6 months (and 12 months for supplementary randomization, if applicable))
- Change from Baseline in SF-36 Score(From baseline to 3, 6, 12, and 24 months after randomization.)
- Change from Baseline in FACT-G Total Score(From baseline to 3, 6, 12, and 24 months after randomization.)
- Safety Endpoints(From first dose to 30 days after last dose or last study visit)
- Change from Baseline in EORTC QLQ-C30 Score(From baseline to 3, 6, 12, and 24 months after randomization.)
研究者
Ding-Wei Ye
Fudan University Shanghai Cancer Center (Fudan University Shanghai Cancer Hospital)
Fudan University