Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer.

Official title

Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer: A Multicenter, Prospective, Randomized Controlled Study

Overview

The goal of this study is to evaluate the efficacy and safety of darolutamide combined with docetaxel and ADT compared to docetaxel combined with ADT in treating locally advanced prostate cancer patients scheduled for radical prostatectomy. The participant population includes adult males with locally advanced prostate cancer (cT3b-cT4, N0, M0 or any cT, N1, M0). The main questions it aims to answer are: Does the combination of darolutamide, docetaxel, and ADT improve treatment outcomes compared to docetaxel combined with ADT? What are the safety profiles and adverse effects associated with each treatment group? Researchers will compare the control group (docetaxel combined with ADT) to the experimental group (darolutamide combined with docetaxel and ADT) to see if the experimental treatment is more effective. Participants will: Receive either docetaxel combined with ADT or darolutamide combined with docetaxel and ADT for 4 cycles (16 weeks) as neoadjuvant treatment. Undergo radical prostatectomy after completing the neoadjuvant treatment. Be followed up for 36 months post-surgery to assess treatment efficacy and safety.

Interventions

• Drug Darolutamide
  Darolutamide: oral administration, 600 mg per dose, twice daily, taken with food.
• Drug docetaxel
  Docetaxel: intravenous injection, 75 mg/m², once every 3 weeks, for a total of 4 doses/cycles. (Oral prednisone acetate should be started 14 days before docetaxel chemotherapy at 5 mg twice daily and discontinued 3 weeks after the last chemotherapy cycle.)
• Drug ADT
  ADT: leuprorelin, goserelin, or triptorelin, selected by the investigator according to the patient's condition, administered by subcutaneous or intramuscular injection, using a once-monthly formulation uniformly.

Primary outcome measures

• 3-year biochemical progression-free survival (bPFS) [Time frame: Every 3 months (±14 days) up to 36 months after surgery]

Secondary outcome measures (12)

• Pathological Downstaging Rate after Radical Prostatectomy [Time frame: On Surgery day]
• Incidence of Treatment-Related Adverse Events [Time frame: From screening visit to 30 days after the last neoadjuvant dose or start of new anticancer therapy]
• Time to Castration-Resistant Prostate Cancer (CRPC) at 3 Years [Time frame: every 3 months PSA tests and every 6 months imaging assessments up to 36 months after surgery]
• Objective Response Rate (ORR) [Time frame: 2-4 weeks after completion of neoadjuvant therapy]
• 3-year Radiographic Progression-Free Survival (rPFS) [Time frame: Every 6 months (±1 month) post-surgery until 36 months post-surgery (months 6, 12, 18, 24, 30, 36)]
• Undetectable PSA Rate post-Radical Prostatectomy [Time frame: 6 weeks post-surgery (±7 days)]
• Subject Quality of Life as assessed by FACT-P( Functional Assessment of Cancer Therapy - Prostate) scale [Time frame: Baseline (V0), post-neoadjuvant/pre-surgery (V5), and at 6, 12, 24, 36 months post-surgery (±14 days)]
• Perioperative Complications [Time frame: From surgery date through 90 days post-surgery]
• Positive Surgical Margin Rate after Radical Prostatectomy [Time frame: On surgery day]
• 3-year biochemical progression-free survival (bPFS) [Time frame: Every 3 months (±14 days) up to 36 months after surgery]
• Time to Castration-Resistant Prostate Cancer (CRPC) at 3 Years [Time frame: PSA tests every 3 months and imaging assessments every 6 months up to 36 months post-surgery]
• Pathological Complete Response (pCR) or Minimal Residual Disease (MRD) Rate [Time frame: On surgery day]

Eligibility criteria

Inclusion criteria

• Male, age >= 18 years and <= 75 years at the time of signing the informed consent form;
• Confirmed as prostate cancer by histological or cytological examination, and planned for radical prostatectomy;
• Clinical stage conforms to the definition of locally advanced prostate cancer: cT3b-cT4, N0, M0 or any cT, N1, M0 (based on PSMA-PET/CT examination);
• Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
• Expected lifespan >= 10 years;
• Important laboratory indicators meet the following requirements: a. Hemoglobin >= 90 g/L b. Serum total bilirubin <= 1.5 times the upper limit of normal value, transaminase (AST/ALT) <= 2.5 times the upper limit of normal value c. Serum albumin >= 30 g/L d. Serum creatinine <= 1.5 times the upper limit of normal value e. Absolute neutrophil count >= 1.5 x 10\^9/L, platelet count >= 100 x 10\^9/L;
• No difficulty in swallowing (can take the medicine in whole), chronic diarrhea, intestinal obstruction or other factors affecting drug administration and absorption;
• No use of opioid analgesics (including codeine, oxycodone, etc.) to relieve cancer pain;
• If the spouse is a fertile female, the subject consents to take effective contraceptive measures during the treatment period and for 4 months after the surgery;
• The subject voluntarily participates in this trial, signs the informed consent form, and is willing to comply with the requirements of the research protocol throughout the study period.

Exclusion criteria

• Pathological diagnosis of neuroendocrine prostate cancer, including small cell carcinoma;
• Prior local or systemic treatment for prostate cancer, including but not limited to radiotherapy, chemotherapy, or endocrine therapy;
• Confirmed bone metastasis, hepatic metastasis, brain metastasis, or other visceral metastases on imaging;
• Known hypersensitivity to the study drugs (active ingredients or excipients) or drugs of the same class;
• Contraindications to prednisone acetate or docetaxel, such as active infection, allergy, or other conditions;
• Chronic disease requiring prednisone acetate at doses exceeding those specified in the protocol (5 mg orally twice daily, starting 14 days before docetaxel chemotherapy and stopping 3 weeks after the last chemotherapy cycle);
• Poorly controlled hypertension despite medication (systolic blood pressure >=160 mmHg or diastolic blood pressure >=95 mmHg);
• Active or symptomatic viral hepatitis or other chronic liver disease; known human immunodeficiency virus (HIV) infection;
• History of pituitary or adrenal dysfunction;
• Active autoimmune disease requiring hormonal therapy;
• Major cardiovascular or cerebrovascular disease within 6 months prior to the start of study treatment, including: severe/unstable angina, myocardial infarction, congestive heart failure \[New York Heart Association (NYHA) class III or above\], cerebrovascular accident, or arrhythmia requiring pharmacological treatment;
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Grade ≥2 peripheral sensory or motor neuropathy;
• Other malignancies occurring within the past 2 years or currently concurrent malignancies;
• Major surgery requiring general anesthesia within 28 days before the first dose;
• Treatment with strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole) or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, St. John's wort) that cannot be discontinued, and have not been stopped for at least 7 days before randomization;
• History of epilepsy;
• Alcohol or drug abuse or dependence;
• Participation in another therapeutic clinical study within 1 month before the start of study treatment;
• Any other condition that the investigator considers unsuitable for participation in this study;

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07730151 · 23233

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗