A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) With ADT in Men With Nonmetastatic Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies

JRCT ID: jRCT2051230094

Registered date:04/09/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: prostate cancer
• Date of first enrollment: 21/09/2023
• Target sample size: 750
• Countries of recruitment: Australia,Japan,Austria,Japan,Brazil,Japan,Canada,Japan,China,Japan,Denmark,Japan,Finland,Japan,France,Japan,Germany,Japan,Israel,Japan,Italy,Japan,New Zealand,Japan,Portugal,Japan,Spain,Japan,Sweden,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Darolutamide (BAY1841788, Nubeqa)
Coated tablet, 300 mg / tablet, oral.
Other: Placebo matching darolutamide
Coated tablet, oral
Other: ADT
Luteinizing hormone-releasing hormone [LHRH] agonist/antagonists

Outcome(s)

• Primary Outcome: Radiological progression-free survival (rPFS) by Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) assessed by Blinded independent central review (BICR)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

- 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 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, or PSA >=2 ng/mL above the nadir after primary RT only.
- Participants must undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) within the 30-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).
- 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 3 months after the last dose of study treatment, and refrain from donating sperm during this period.

Exclude 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.

Related Information

• Primary Sponsor: Tanigawa Takahiko
• Secondary ID(s): NCT05794906