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Neoadjuvant Therapy of Darolutamide Plus ADT for High Risk Prostate Cancer

Phase 2
Recruiting
Conditions
Prostate Cancer
Interventions
Registration Number
NCT06575257
Lead Sponsor
Xijing Hospital
Brief Summary

The purpose of this study is to determine if treatment with Darolutamide plus androgen deprivation therapy (ADT) before radical prostatectomy (RP) with pelvic lymph node dissection (pLND) in participants with high-risk localized or locally advanced prostate cancer results in an improvement in pathological complete response (pCR) rate and pathological tumor volume with minimal residual disease (MRD)) as compared to ADT.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
80
Inclusion Criteria
  • Patients must be ≥ 18 and ≤75 years of age.
  • All patients must have a histologically or cytologically diagnosis of prostate cancer and must be eligible for radical prostatectomy.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score ≤1.
  • All patients must complete mpMRI or 68Ga-PSMA PET / CT before and after neoadjuvant treatment.
  • All patients must undergo thorough tumor staging and meet one of the following criteria: 1. multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ cT2c or cN+or locally advanced, 2. Gleason score of primary tumor ≥ 8, 3. prostate specific antigen (PSA) ≥20 ng/ml.
  • Patients must have adequate organ function as defined by the following criteria(within 28 days prior to registration):

white blood cell (WBC) ≥ 4.0 × 109 / L platelets≥ 100 × 109 / L hemoglobin ≥ 9 g / dL international normalized ratio (INR) < 1.5. total bilirubin (TBIL)≤1.5 x upper limit of normal (ULN) SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN serum creatinine ≤2×ULN

  • Patients must participate voluntarily and sign an informed consent form (ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must be willing to obey the prohibitions and restrictions specified in the research protocol.
Exclusion Criteria
  • clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases.
  • Prior androgen deprivation therapy (medical or surgical) or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy.
  • severe or uncontrolled concurrent infections.
  • New York Heart Association Class III or IV congestive heart failure at the time of screening.
  • uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
  • Patients with mental illness, mental disability or inability to give informed consent are not eligible.
  • Patients have had other malignancies other than prostate cancer in the past 5 years, but cured basal cell or squamous cell skin cancers can be enrolled.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Darolutamide Plus ADTGoserelin 3.6 mgAll participants in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus Darolutamide. Goserelin 3.6 mg will be used once per 4 weeks. Darolutamide will be administered orally as 600 mg twice a day. Subjects will continue to take Darolutamide Plus Goserelin for 12 weeks before radical prostatectomy
ADT aloneGoserelin 3.6 mgAll participants in this arm will receive LHRHa alone for 12 weeks before receiving radical prostatectomy. Goserelin 3.6 mg will be administered once per 4 weeks.
Darolutamide Plus ADTDarolutamideAll participants in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus Darolutamide. Goserelin 3.6 mg will be used once per 4 weeks. Darolutamide will be administered orally as 600 mg twice a day. Subjects will continue to take Darolutamide Plus Goserelin for 12 weeks before radical prostatectomy
Primary Outcome Measures
NameTimeMethod
Pathologic Complete Response RateAfter 12 weeks of neoadjuvant therapy + RP + PLND

The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy

Proportion of Subjects With Minimal Residual DiseaseAfter 12 weeks of neoadjuvant therapy + RP + PLND

The proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy

Secondary Outcome Measures
NameTimeMethod
Proportion of subjects without PSA progression2 years after RP

The proportion of subjects whose PSA has never gone below 1 ng/ml or who receive any radiotherapy or systemic treatment after radical prostatectomy

Imaging Response RateAfter 12 weeks of neoadjuvant therapy

The proportion of subjects whose primary tumor is in complete remission on imaging or residual tumor's maximum diameter is less than 0.5cm

Rate of Complete Serum RemissionAfter 12 weeks of neoadjuvant therapy

The proportion of subjects whose PSA is less than or equal to 0.2 ng/ml after 3 months of treatment

Recovery time of urinary continence (day)1 years after RP

The recovery time of urinary continence (day) after radical prostatectomy, defined as 0 pad/day.

Rate of Positive Surgical MarginsAfter 12 weeks of neoadjuvant therapy + RP + PLND

The proportion of subjects with positive surgical margins after radical prostatectomy

Rate of Stage DegradationAfter 12 weeks of neoadjuvant therapy + RP + PLND

Clinical or pathological stage degradation after neoadjuvant therapy

biochemical recurrence-free survival (bRFS)3 years after RP

biochemical recurrence-free survival (bRFS) defined as time to PSA ≥ 0.2 ng/ml after radical prostatectomy.

metastasis-free survival (MFS)5 years after RP

time from date of randomization to date of evidence of systemic disease on bone scan or cross-sectional imaging.

Trial Locations

Locations (1)

The First Affillated Hospital, the Air Force Medical University

🇨🇳

Xi'an, Shanxi, China

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