A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide Plus Androgen Deprivation Therapy (ADT) Compared With Placebo Plus ADT in Patients With High-risk Biochemical Recurrence (BCR) of Prostate Cancer

Condition: Biochemically Recurrent Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05794906

Sponsor: Bayer

Phase: Phase 3


  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Capable of giving signed informed consent as described which includes compliance with the requirements, restrictions listed in the informed consent form (ICF), and in this protocol.
  • Male ≥18 years of age at the time of signing the informed consent.
  • Histologically or cytologically confirmed adenocarcinoma of prostate.
  • Prostate cancer initially treated by: radical prostatectomy (RP) followed by adjuvant radiotherapy (ART), or salvage radiotherapy (SRT), or RP in participants who are unfit (or refused) for ART or SRT, or primary radiotherapy (RT).
  • High-risk biochemical recurrence (BCR), defined as Prostate-specific antigen doubling time (PSADT) <12 months calculated using the formula provided by the Sponsor, and PSA ≥0.2 ng/mL after ART or SRT post RP or after RP in participants who are unfit for ART or SRT (local or central values accepted), or PSA ≥2 ng/mL above the nadir after primary RT only (local or central values accepted).
  • Participants must undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) within the 42-day Screening period using either 18F-DCFPyL (piflufolastat F 18) or 68Ga-PSMA-11 which will be assessed by blinded independent central review (BICR) to identify at least one PSMA PET/CT lesion of prostate cancer.
  • Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local or central values accepted).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Blood counts at screening: Hemoglobin ≥9.0 g/dL (participant must not have received blood transfusion within 7 days prior to sample being taken); Absolute neutrophil count (ANC) ≥1.5x10^9/L (participant must not have received any growth factor within 4 weeks prior to sample being taken); Platelet count ≥100x10^9/L.
  • Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN, (except participants with a diagnosis of Gilbert's disease); Estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula.
  • Sexually active male participants must agree to use contraception as detailed in the protocol during the Treatment period and for at least 1 week after the last dose of study treatment, and refrain from donating sperm during this period.

Exclusion Criteria:

  • Pathological finding consistent with small cell, ductal or ≥50 % component of neuroendocrine carcinoma of the prostate.
  • History of bilateral orchiectomy.
  • Metastases or recurrent /new malignant lesions in prostate gland/bed seminal vesicles, lymph nodes below the CIA bifurcation on conventional imaging (CI) as assessed by BICR during screening.
  • Brain metastasis on PSMA PET /CT by BICR at screening.
  • High-risk BCR after primary radiotherapy with new loco-regional lesions on screening PSMA PET/CT who are eligible for curative salvage prostatectomy. Note: Participants treated with curative salvage prostatectomy after primary RT who meet the PSA criteria (inclusion criteria 5) may be considered for the study.
  • Prior treatment with second generation (e.g. enzalutamide, apalutamide) androgen receptor inhibitors (ARIs) and CYP 17 inhibitors (e.g., abiraterone) within 18 months prior to signing of the ICF.
  • Prior treatments with PSMA-radiotherapeutics within 12 months prior to randomization.
  • Prior radiotherapy (including image-guided radiotherapy) as primary, adjuvant or salvage treatment completed within 8 weeks prior to signing of the ICF.
  • Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years.
  • History of pelvic radiotherapy for other malignancy.

View trial on ClinicalTrials.gov