Rezvilutamide Combined With Radical Prostatectomy and Metastasis-Directed Radiotherapy in Oligometastatic Prostate Cancer Patients: A Multicenter, Three-Arm, Open-Label, Randomized Controlled Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Prostate cancer represents the second most common malignancy in men worldwide. Oligometastatic prostate cancer (OMPC), defined as a transitional state between localized and widespread metastatic disease (≤10 metastatic lesions without visceral metastases), exhibits relatively indolent biological behavior, offering a window for curative-intent multimodal therapy. While standard systemic therapy with androgen deprivation therapy (ADT) plus novel hormonal agents (NHA) remains the backbone for metastatic hormone-sensitive prostate cancer (mHSPC), emerging evidence suggests that maximal cytoreductive therapy-combining systemic treatment with local interventions (Radical prostatectomy（RP） and Metastasis-directed radiotherapy（MDT）)-may improve survival outcomes. Rezvilutamide (SHR3680), a novel androgen receptor inhibitor independently developed by a Chinese pharmaceutical company, has demonstrated superior radiographic progression-free survival (rPFS) and overall survival (OS) compared to bicalutamide in high-volume mHSPC (CHART study). However, the value of adding metastasis-directed radiotherapy (MDRT) to rezvilutamide and radical prostatectomy in OMPC remains unproven. This trial hypothesizes that maximal cytoreductive therapy (systemic therapy + surgery + MDRT) will significantly prolong progression-free survival (PFS) compared to systemic therapy alone.
This is a multicenter, three-arm, open-label, randomized controlled phase II clinical trial (Protocol No.: MA-PCa-II-023; Lead Investigator: Prof. Bo Dai, Fudan University Shanghai Cancer Center). The study will enroll 300 patients randomized in a 2:2:1 ratio to:
Arm A (Experimental): Rezvilutamide (240 mg QD) + ADT → radical prostatectomy at month 3 (if PSA decline ≥50%, castrate testosterone level, and resectable disease) → MDT (SBRT 30-40 Gy/3-5 fractions) to all evaluable metastases at month 6 （ 3 month post-surgery）
Arm B (Control): Rezvilutamide (240 mg QD) + ADT alone
Arm C (Factorial): Rezvilutamide (240 mg QD) + ADT → radical prostatectomy at month 3 (without MDT)
Eligible patients are males ≥18 years with histologically confirmed prostate adenocarcinoma (no neuroendocrine differentiation), newly diagnosed mHSPC with oligometastatic disease (≤10 bone/lymph node metastases on conventional imaging; no visceral metastases), and planned ADT. Key exclusion criteria include prior radical prostatectomy, pelvic radiotherapy, systemic therapy for prostate cancer (except ≤4 weeks of ADT), or contraindications to surgery/radiotherapy.
The primary endpoint is PFS, defined as time from randomization to first biochemical progression (PSA rise ≥25% and ≥1 ng/mL above nadir confirmed after ≥3 weeks), radiographic progression (RECIST 1.1/PCWG4), clinical progression (new symptoms from local/metastatic disease), or death. Secondary endpoints include rPFS, OS, PSA response rates (PSA50/PSA90), local therapy completion rate, time to CRPC, quality of life (FACT-P and EPIC-26 questionnaires), and safety profiles. Exploratory endpoints evaluate the role of baseline PSMA PET/CT in staging and the development of artificial intelligence models using multimodal data (clinical, imaging, pathology, molecular) to predict prognosis.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation with signed informed consent and understanding of study procedures.
- •Age ≥18 years.
- •Histologically or cytologically confirmed prostatic adenocarcinoma without neuroendocrine differentiation, small cell, sarcomatoid, spindle cell, or signet ring cell histology.
- •Metastatic hormone-sensitive prostate cancer (mHSPC) with oligometastatic disease defined as: a) ≤10 metastatic lesions combined (bone lesions on Tc-99m bone scan plus extra-pelvic lymph nodes on CT/MRI); and b) No visceral metastases on CT/MRI.
- •Planned or ongoing androgen deprivation therapy (ADT) with LHRH agonist/antagonist (medical castration) or prior bilateral orchiectomy (surgical castration) within ≤4 weeks before enrollment.
- •Adequate organ function (without transfusion or hematopoietic growth factor support within 2 weeks prior to screening labs):
- •Absolute neutrophil count (ANC) ≥1.5×10⁹/L
- •Platelet count (PLT) ≥100×10⁹/L
- •Hemoglobin (Hb) ≥90 g/L
- •Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance >50 mL/min
- •Total bilirubin (BIL) ≤1.5×ULN
- •AST/SGOT or ALT/SGPT ≤2.5×ULN
- •International normalized ratio (INR) ≤1.5, PT and APTT ≤1.5×ULN
- •Left ventricular ejection fraction (LVEF) ≥50%
- •Male patients with female partners of childbearing potential must agree to use effective contraception during the study and for 3 months after the last dose, and must not donate sperm during this period.
- •Ability to comply with the study protocol as judged by the investigator.
- •Ability to adhere to scheduled visits, treatment plans, and laboratory assessments.
排除标准
- •Prior radical prostatectomy, pelvic radiotherapy, prostatic ablation, or any systemic anti-prostate cancer therapy (including novel hormonal therapy, chemotherapy, radionuclide therapy, cancer vaccines, or immune checkpoint inhibitors), except ADT initiated ≤4 weeks prior to randomization that meets inclusion criteria.
- •Prior radiotherapy to prostate cancer metastases.
- •Known visceral metastases (liver, lung, brain, peritoneum, etc.) or diffuse bone marrow metastases.
- •Severe contraindications to surgery or radiotherapy, including major cardiovascular disease (e.g., NYHA Class III-IV heart failure, recent myocardial infarction), pulmonary insufficiency unable to tolerate anesthesia, severe bleeding tendency, or bone marrow suppression.
- •Other prior or concurrent malignancies, unless basal cell carcinoma of the skin or other cancers cured for >5 years.
- •Active infections, including active hepatitis B (HBV DNA >2×10³ IU/mL), hepatitis C RNA positive with hepatic impairment, HIV infection, or inadequately treated syphilis.
- •Uncontrolled major cardiovascular disease within 6 months prior to screening, including: a) unstable angina or recent myocardial infarction (within 6 months); b) clinically significant arrhythmias (e.g., sustained ventricular tachycardia); c) heart failure (NYHA Class ≥III).
- •Severe hepatic or renal dysfunction or other laboratory abnormalities not meeting the organ function requirements specified in Inclusion Criterion #
- •Known hypersensitivity or history of severe adverse reactions to study medications (novel hormonal agents), anesthetics, or contrast agents used in the study.
- •Any medical, psychological, or social factors that may affect patient compliance or interfere with study outcome assessment, including psychiatric disorders, substance abuse, or other conditions deemed unsuitable by the investigator.
- •Concurrent participation in another interventional clinical study, or use of any investigational drug or medical device within 4 weeks prior to randomization.
- •Any other condition that the investigator considers unsuitable for study participation.
结局指标
主要结局
Progression-free survival (PFS)
时间窗: up to 72 months
Time from randomization to the first occurrence of biochemical progression, radiographic progression, clinical progression, or death. Biochemical progression: (1) For patients with PSA decline from baseline: PSA increase ≥25% and ≥1 ng/mL above nadir, confirmed by repeat testing ≥3 weeks later; or (2) For patients without PSA decline: PSA increase ≥25% and ≥1 ng/mL above baseline after ≥12 weeks of treatment. Radiographic progression: Disease progression per RECIST 1.1 (soft tissue) and PCWG4 (bone) criteria. Clinical progression: New symptoms due to local disease progression, lymph node involvement, or systemic metastases (e.g., pathologic fracture, spinal cord compression, worsening pain unresponsive to symptomatic treatment).
次要结局
- PSA Response Rates(up to 72 months)
- Radiographic PFS (rPFS)(up to 72 months)
- Overall Survival (OS)(up to 72 months)
- Local Therapy Completion Rate(up to 72 months)
- Time to CRPC(up to 72 months)
- 3-Year PSA Progression-Free Survival Rate(up to 72 months)
- Time to PSA Progression(up to 72 months)