Rezvilutamide With Radical Prostatectomy and Metastasis-Directed Therapy in Oligometastatic Prostate Cancer

Summary

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.

Conditions

• Oligometastatic Prostate Cancer

Interventions

RADIATION

Metastasis-directed radiotherapy

Metastasis-directed radiotherapy (MDRT; SBRT 30-40 Gy/3-5 fractions to all evaluable metastases) at 3 months post-surgery

DRUG

Rezvilutamide + ADT

Rezvilutamide (240 mg daily) plus ADT alone until progression or unacceptable toxicity.

PROCEDURE

Radical prostatectomy

Radical prostatectomy with extended pelvic lymph node dissection (ePLND), including removal of the prostate gland, seminal vesicles, and bilateral pelvic lymph node groups (obturator, internal iliac, external iliac, and common iliac nodes), performed in patients with oligometastatic prostate cancer

Sponsors & Collaborators

• Jiangsu Hengrui Pharmaceutical Co., Ltd.

  collaborator INDUSTRY

• Fudan University

  lead OTHER

Principal Investigators

• Bo Dai, MD · Fudan University Shanghai Cancer Cente

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-01

Primary Completion

2032-05-31

Completion

2032-05-31

Countries

• China

Study Locations