Comparing a 6-month vs Long-term Course of Rezvilutamide With ADT Plus Chemotherapy in mHSPC

A Multi-center, Randomized, Open-label Clinical Trial Comparing a 6-month vs Long-term Course of Rezvilutamide With ADT Plus Chemotherapy in High Tumor Burden mHSPC

Primary Objective:

To explore whether a 6-month course of Rezvilutamide in the triple therapy regimen is non-inferior to long-term Rezvilutamide treatment in improving radiographic progression-free survival (rPFS) in patients with high tumor burden metastatic hormone-sensitive prostate cancer (mHSPC).

Secondary Objectives:

To evaluate and compare the time to prostate-specific antigen (PSA) progression, time to next bone-related event, time to initiation of subsequent anti-prostate cancer treatment, and objective response rate (ORR) between the 6-month and long-term course of Rezvilutamide with androgen deprivation therapy (ADT) plus docetaxel in patients with high tumor burden mHSPC.

To assess and compare the incidence of adverse events between the 6-month and long-term course of Rezvilutamide with ADT plus docetaxel in patients with high tumor burden mHSPC.

Exploratory Objectives:

To observe the circulating tumor cell status at 6 months, 12 months, 18 months, and 24 months in patients with high tumor burden mHSPC receiving the triple therapy regimen.

Primary Study Endpoints:

Radiographic progression-free survival (rPFS)

Secondary Study Endpoints:

Time to prostate-specific antigen (PSA) progression Time to next bone-related event (including fractures, spinal cord compression, radiation therapy, or surgery targeting the bones) Time to initiation of subsequent anti-prostate cancer treatment Objective response rate (ORR) Quality of life assessment scores

Inclusion Criteria:

• Inclusion criteria:

  1. Age ≥ 18 years, male.

  2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

  3. Histologically or cytologically confirmed prostate adenocarcinoma without evidence of neuroendocrine or small cell features.

  4. High tumor burden, defined as having at least one of the following conditions: 1) Bone scan showing ≥4 bone metastatic lesions (with at least one site outside the pelvis or spine). 2) CT/MRI revealing visceral metastatic lesions (excluding lymph nodes).

  5. Planned to receive or maintain androgen deprivation therapy (ADT) during the study period, either by continuous LHRHa treatment or previous bilateral orchiectomy (surgical castration), concurrently with 6 cycles of docetaxel chemotherapy.

  6. Organ function levels must meet the following requirements:

     • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L.
     • Platelets (PLT) ≥ 100 × 10^9/L.
     • Hemoglobin (Hb) ≥ 90 g/L.
     • Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN).
     • Alanine aminotransferase (ALT) ≤ 2.5 × ULN.
     • Aspartate aminotransferase (AST) ≤ 2.5 × ULN.
     • Blood urea nitrogen (BUN) (or urea) and creatinine (Cr) ≤ 1.5 × ULN.
     • Left ventricular ejection fraction (LVEF) ≥ 50%.

  7. Judged by the investigator to be able to comply with the trial protocol.

  8. Voluntarily participate in the clinical trial, understand the study procedures, and have signed the informed consent form.

Exclusion Criteria:

1. Prior treatment with ADT, chemotherapy, surgery, external beam radiation therapy, brachytherapy, radiopharmaceuticals, or investigational local therapies for prostate pain. However, the following cases are allowed for inclusion:

   • Up to 3 months of ADT (medical or surgical castration) with or without antiandrogen therapy prior to Cycle 1 Day 1 (C1D1) without evidence of radiographic disease progression (based on RECIST 1.1 criteria) or clinically significant PSA rise (defined as ≥50% increase from the lowest level after reaching castration levels of serum testosterone) before C1D1.
   • Transurethral prostatectomy or up to one course of palliative radiation therapy or surgery for symptomatic treatment of metastatic disease at least 4 weeks prior to C1D1. All adverse events related to these treatments must have improved to at least Grade 1 (according to NCI-CTCAE v4.03) before starting study treatment.

2. Prior use or planned use of second-generation androgen receptor antagonists (such as enzalutamide, apalutamide, darolutamide), abiraterone acetate, or other investigational drugs inhibiting testosterone synthesis for the treatment of prostate cancer during the study period.

3. Received the following treatments within 4 weeks before C1D1:

   • 5-alpha-reductase inhibitors (e.g., finasteride, dutasteride).
   • Estrogens, progestins, androgens, systemic corticosteroids (except for temporary use for allergic purposes).
   • Known herbal medicines with anti-prostate cancer or PSA-lowering effects (e.g., saw palmetto).
   • Participation in other clinical trials involving investigational treatments.

4. Confirmed brain tumor lesions on imaging.

5. Planned to receive any other anticancer treatment during the trial.

6. Known allergy or hypersensitivity to apalutamide, ADT, or chemotherapy components.

7. Presence of conditions that impede swallowing, chronic diarrhea, intestinal obstruction, or other factors affecting drug intake and absorption.

8. History of seizures or occurrence of conditions that can induce seizures within 12 months before C1D1 (including transient ischemic attack, stroke, traumatic brain injury with altered consciousness requiring hospitalization).

9. Presence of active cardiac diseases within 6 months before C1D1, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and ventricular arrhythmias requiring medication.

10. Diagnosis of any other malignancy within 5 years before C1D1, except for completely resolved in situ cancer or malignancies with slow progression as determined by the investigator.

11. Active HBV or HCV infection (HBV viral load ≥ 10,000 copies/mL, HCV viral load ≥ 1,000 copies/mL).

12. History of immunodeficiency (including positive HIV test) or organ transplantation.

13. Unwillingness to use effective contraception during the entire study treatment period and for 30 days after the last dose.

14. Judged by the investigator to have conditions that pose a serious risk to patient safety, may confound study results, or may affect the patient's ability to complete the study (such as poorly controlled hypertension, severe diabetes, neurological or psychiatric diseases, etc.), or any other relevant circumstances.