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

NCT ID: NCT07268794

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2027-12-30

Brief Summary

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Androgen Deprivation Therapy (ADT)

Intervention Type: DRUG

Androgen deprivation therapy using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) according to local prescribing information and CSCO guideline recommendations. The specific drug, dose, and schedule are determined by the investigator and may be adjusted based on tolerability and adverse events.

Docetaxel

Intervention Type: DRUG

Intravenous docetaxel may be combined with ADT plus second-generation ARSis in selected patients according to contemporary guideline recommendations and investigator judgment. Dose and schedule follow approved labels and may be modified based on toxicity and tolerability.

PARP Inhibitors and Other Systemic Agents

Intervention Type: DRUG

Other systemic agents, including PARP inhibitors such as olaparib, may be used in combination with ADT and second-generation ARSis according to approved indications, molecular testing results, guideline recommendations, and investigator judgment.

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

Group Type: EXPERIMENTAL

Androgen Deprivation Therapy (ADT)

Intervention Type: DRUG

Androgen deprivation therapy using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) according to local prescribing information and CSCO guideline recommendations. The specific drug, dose, and schedule are determined by the investigator and may be adjusted based on tolerability and adverse events.

Docetaxel

Intervention Type: DRUG

Intravenous docetaxel may be combined with ADT plus second-generation ARSis in selected patients according to contemporary guideline recommendations and investigator judgment. Dose and schedule follow approved labels and may be modified based on toxicity and tolerability.

PARP Inhibitors and Other Systemic Agents

Intervention Type: DRUG

Other systemic agents, including PARP inhibitors such as olaparib, may be used in combination with ADT and second-generation ARSis according to approved indications, molecular testing results, guideline recommendations, and investigator judgment.

Radical Prostatectomy

Intervention Type: PROCEDURE

Radical prostatectomy with bilateral seminal vesicle removal and, when appropriate, pelvic lymph node dissection, performed by experienced urologic surgeons via open, laparoscopic, or robot-assisted approach, in patients randomized to Arm B who have achieved conversion success on PSMA PET/CT

Prostate Radiotherapy

Intervention Type: RADIATION

Definitive external-beam radiotherapy to the prostate delivered according to institutional standards and guideline recommendations, as an alternative local prostate treatment for patients randomized to Arm B who have achieved conversion success on PSMA PET/CT and are not undergoing radical prostatectomy

Interventions

Androgen Deprivation Therapy (ADT)

Androgen deprivation therapy using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) according to local prescribing information and CSCO guideline recommendations. The specific drug, dose, and schedule are determined by the investigator and may be adjusted based on tolerability and adverse events.

Intervention Type: DRUG

Docetaxel

Intravenous docetaxel may be combined with ADT plus second-generation ARSis in selected patients according to contemporary guideline recommendations and investigator judgment. Dose and schedule follow approved labels and may be modified based on toxicity and tolerability.

Intervention Type: DRUG

PARP Inhibitors and Other Systemic Agents

Other systemic agents, including PARP inhibitors such as olaparib, may be used in combination with ADT and second-generation ARSis according to approved indications, molecular testing results, guideline recommendations, and investigator judgment.

Intervention Type: DRUG

Radical Prostatectomy

Radical prostatectomy with bilateral seminal vesicle removal and, when appropriate, pelvic lymph node dissection, performed by experienced urologic surgeons via open, laparoscopic, or robot-assisted approach, in patients randomized to Arm B who have achieved conversion success on PSMA PET/CT

Intervention Type: PROCEDURE

Prostate Radiotherapy

Definitive external-beam radiotherapy to the prostate delivered according to institutional standards and guideline recommendations, as an alternative local prostate treatment for patients randomized to Arm B who have achieved conversion success on PSMA PET/CT and are not undergoing radical prostatectomy

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Ding-Wei Ye

Fudan University Shanghai Cancer Center (Fudan University Shanghai Cancer Hospital)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan University Shanghai Cancer Center

Shanghai, , China

Countries

China

Central Contacts

Dingwei Ye, MD.

Role: CONTACT

dwyeli@163.com

86-21-64175590

Xiaojian Qin, MD.

Role: CONTACT

q@urocancer.org

+86 18017317217

Facility Contacts

Dingwei Ye

Role: primary

dwyeli@163.com

86-21-64175590

References

Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. doi: 10.1200/JCO.2017.75.3657. Epub 2018 Jan 31.

Reference Type: BACKGROUND

PMID: 29384722 (View on PubMed)

Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, Lambert B, Delrue L, Bultijnck R, Claeys T, Goetghebeur E, Villeirs G, De Man K, Ameye F, Billiet I, Joniau S, Vanhaverbeke F, De Meerleer G. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol. 2018 Feb 10;36(5):446-453. doi: 10.1200/JCO.2017.75.4853. Epub 2017 Dec 14.

Reference Type: RESULT

PMID: 29240541 (View on PubMed)

Other Identifiers

MNWKQXJ20251102

Identifier Type: -

Identifier Source: org_study_id