CONVERT-HB1: Radical Prostatectomy After Systemic Therapy for High-volume Metastatic Hormone-sensitive Prostate Cancer

Fudan University

Status and phase: Not yet enrolling; Phase 2

Conditions: Metastatic Prostate Cancer; Prostate Cancer (Adenocarcinoma); Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Treatments: Radiation: Prostate Radiotherapy; Drug: PARP Inhibitors and Other Systemic Agents; Drug: Androgen Deprivation Therapy (ADT); Procedure: Radical Prostatectomy; Drug: Docetaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT07268794

MNWKQXJ20251102

Details and patient eligibility

About

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.

Enrollment: 112 estimated patients

Sex: Male

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male patients aged >18 and ≤70 years, or with an estimated life expectancy >10 years.
2. Histologically or cytologically confirmed prostate adenocarcinoma with neuroendocrine differentiation ≤10%, and no small cell or signet-ring cell carcinoma component.
3. 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).
4. Newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) who started intensified endocrine therapy within 3 months.
5. ECOG performance status 0-2.
6. 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).
7. Patients voluntarily sign informed consent and are willing and able to comply with study procedures.

Exclusion criteria

1. History of hypersensitivity or intolerance to any study drugs.
2. mCRPC (metastatic castration-resistant prostate cancer).
3. Oligometastatic mHSPC intended for upfront radical prostatectomy.
4. 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.
5. Major surgery within 4 weeks prior to starting study treatment.
6. 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).
7. Conditions affecting drug intake or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction).
8. Active infection (e.g., HIV positive, HBsAg positive, HCV positive) which in the investigator's opinion may affect safety or efficacy assessment.
9. Other malignancies within the past 3 years, except adequately treated basal cell carcinoma of the skin.
10. Known brain metastases or leptomeningeal disease.
11. Concurrent participation in another interventional clinical trial or receiving other investigational drugs/devices.
12. Poor compliance or inability to adhere to study procedures and follow-up.
13. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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112 participants in 2 patient groups

Systemic Therapy Alone

Active Comparator group

Description:

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

Treatment:

Drug: Docetaxel

Drug: Androgen Deprivation Therapy (ADT)

Drug: PARP Inhibitors and Other Systemic Agents

Systemic Therapy Plus Local Prostate Treatment (Arm B)

Experimental group

Description:

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

Treatment:

Drug: Docetaxel

Procedure: Radical Prostatectomy

Drug: Androgen Deprivation Therapy (ADT)

Drug: PARP Inhibitors and Other Systemic Agents

Radiation: Prostate Radiotherapy