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

Official title

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)

Overview

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.

Interventions

• Drug 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.
• 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.
• 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.
• Procedure 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
• Radiation 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

Primary outcome measures

• Radiographic Progression-free Survival (rPFS) [Time frame: From randomization to radiographic progression or death from any cause, whichever occurs first, up to approximately 24 months.]

Secondary outcome measures (8)

• Overall Survival (OS) [Time frame: 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) [Time frame: From start of systemic therapy to biochemical progression or death, up to ~24 months.]
• PSA Response Rate at 3 and 6 Months [Time frame: 3 months and 6 months after treatment]
• Conversion Success Rate [Time frame: At 6 months (and 12 months for supplementary randomization, if applicable)]
• Safety Endpoints [Time frame: From first dose to 30 days after last dose or last study visit]
• Change from Baseline in EORTC QLQ-C30 Score [Time frame: From baseline to 3, 6, 12, and 24 months after randomization.]
• Change from Baseline in SF-36 Score [Time frame: From baseline to 3, 6, 12, and 24 months after randomization.]
• Change from Baseline in FACT-G Total Score [Time frame: From baseline to 3, 6, 12, and 24 months after randomization.]

Eligibility criteria

Inclusion criteria

• 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 0-2.
• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Publications

• 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. PMID 29384722
• 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. PMID 29240541

Identifiers

NCT: NCT07268794 · MNWKQXJ20251102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗