Deutenzalutamide and Hormone Therapy Before and After Surgery With Docetaxel Before Surgery for High-Risk Localized or Locally Advanced Prostate Cancer

Korábbi kezelés

• Neuroendocrine/small-cell prostate carcinoma, distant metastases, or previous local or systemic treatment for prostate cancer.
• Serious cardiovascular/cerebrovascular disease within 6 months before study treatment, including severe/unstable angina, myocardial infarction, New York Heart Association class III-IV heart failure, stroke, or arrhythmia requiring medication.
• Previous allogeneic organ or hematopoietic stem-cell transplantation.
• Another malignancy currently or within the previous 2 years.
• Major surgery requiring general anesthesia within 28 days before the first dose.
• Use of prohibited urinary-symptom or PSA-altering medications during deutenzalutamide treatment, including finasteride, dutasteride or phytoestrogens.
• Alcohol or drug abuse/dependence.
• Participation in another therapeutic clinical trial within 1 month before study treatment.

Más betegség

• Allergy to study drugs, excipients or drugs of the same class; contraindications to docetaxel or prednisone acetate, including active infection.
• Poorly controlled hypertension despite treatment: systolic \>=160 mmHg or diastolic \>=95 mmHg.
• Active or symptomatic viral hepatitis or other chronic liver disease; known HIV infection.
• History of pituitary or adrenal dysfunction; active autoimmune disease requiring corticosteroids.
• Seizure history or conditions increasing seizure risk, including stroke within 1 year before the first study anticancer dose or cerebral arteriovenous malformation; benign central nervous system/meningeal disease expected to require surgery or radiotherapy during study treatment.
• Any other condition considered unsuitable by the investigator.

Egyéb

• Need for chronic systemic glucocorticoids exceeding a total prednisone-equivalent dose of 10 mg/day during study treatment.
• Grade \>=2 peripheral sensory or motor neuropathy.

• Inclusion Criteria:
• Men aged 18-80 years with histologically confirmed high-risk localized or locally advanced prostate adenocarcinoma.
• High-risk disease is defined by meeting either (1) or (2):
  • NCCN high-risk criteria: at least one of the following:Gleason score \>=8;Prostate-specific antigen (PSA) \>=20 ng/mL;Clinical T stage \>=T3.
  • Study-specific biopsy criteria: overall Gleason score \>=4+3 (International Society of Urological Pathology \[ISUP\] Grade Group \[GG\] 3-5), plus at least one of the following:(a) \>=6 systematic biopsy cores showing Gleason 4+3 (GG3) or Gleason 8 (4+4 or 5+3), including at least one Gleason-8 core. Only systematic cores are counted; targeted cores are excluded from this count;(b) \>=3 systematic biopsy cores showing Gleason 4+3 (GG3) or Gleason 8 (4+4 or 5+3), PSA \>=20 ng/mL, and at least one Gleason-8 core. Only systematic cores are counted; targeted cores are excluded from this count;(c) \>=1 systematic or targeted biopsy core with Gleason score \>=9 (GG5). Both systematic and targeted cores may be counted, without counting the same core more than once;(d) \>=2 distinct, evaluable systematic or targeted biopsy cores, each with Gleason score \>=8 (GG4-5) and tumor involvement \>=80%. Core counting and tumor involvement are determined according to the protocol's standardized rules.
• No distant metastases (cM0) on baseline imaging; cN0 or pelvic cN1 below the common iliac artery bifurcation is permitted. Suitable for radical prostatectomy and pelvic lymph node dissection.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy \>=10 years; able to receive androgen-deprivation therapy for \>=13 months.
• Adequate organ function, assessed after \>=14 days without blood-component transfusion or hematopoietic support: neutrophils \>=1.5 x 10\^9/L; platelets \>=100 x 10\^9/L; hemoglobin \>=9 g/dL; potassium \>=3.5 mmol/L; ALT and AST \<=2.5 times the upper limit of normal (ULN); total bilirubin \<=1.5 x ULN; creatinine \<1.5 x ULN; albumin \>=3.0 g/dL; international normalized ratio (INR) \<1.5. Eligibility during therapeutic anticoagulation requires investigator assessment.
• Able to swallow capsules, without significant swallowing difficulty or a history of severe gastrointestinal malabsorption.
• Written informed consent and willingness to comply with study procedures and applicable contraception requirements.