for males ages 18 years and up (full criteria)
at Orange, California and other locations
study started
estimated completion



Researchers are looking for a better way to treat men at high-risk of biochemical recurrence (BCR) of prostate cancer.

BCR means that in men who had prostate cancer and were treated by either surgery and/ or radiation therapy, the blood level of a specific protein called PSA rises. PSA is a marker for prostate cancer development. This may mean that the cancer has come back even though no cancer or cancer spreading is yet detectable using conventional imaging such as computed tomography (CT) scans, magnetic resonance imaging (MRI) and bone scans. Recently a more sensitive imaging method called prostate-specific membrane antigen [PSMA] positron emission tomography [PET]) /computed tomography [CT]) scan may identify prostate cancer lesions not detectable by conventional imaging. Men with BCR have a higher risk of their cancer spreading to other parts of the body, particularly men with a stage of prostate cancer where the PSA levels raised to a certain limit within a specified period of time after local therapies. Once the cancer spreads to other parts of the body, it can become even harder to treat.

In men with prostate cancer, male sex hormones (also called androgens) like testosterone can help the cancer grow and spread. To reduce androgens levels in these patients, there are treatments that block androgens production in the body called androgen deprivation therapy (ADT). ADT is often used to stop prostate cancer. Another way to stop prostate cancer growth and spread is to block the action of androgen receptors on prostate cancer cells. Next generation androgen receptor inhibitors (ARIs) including darolutamide can block the action of androgens receptors and are available for the treatment of prostate cancer in addition to ADT. It is already known that men with prostate cancer benefit from these treatments.

The main objective of this study is to learn if the combination of darolutamide and ADT prolongs the time that the participants live without their cancer getting worse, or to death due to any cause, compared to placebo and ADT given for 24 months. A placebo is a treatment that looks like a medicine but does not have any medicine in it.

To do this, the study team will measure the time from the date of treatment allocation to the finding of new cancer spread in the participants by using PSMA PET/CT, or death due to any cause. The PSMA PET/CT scans is performed using a radioactive substance called a "tracer" that specifically binds to the prostate-specific membrane antigen (PSMA) which is a protein often found in large amounts on prostate cancer cells.

To avoid bias in treatment, the study participants will be randomly (by chance) allocated to one of two treatment groups. Based on the allocated treatment group, the participants will either take darolutamide plus ADT or placebo plus ADT twice daily as tablets by mouth. The study will consist of a test (screening) phase, a treatment phase and a follow-up phase. The treatment duration will be 24 months unless the cancer gets worse, the participants have medical problems, or they leave the study for any reason. In addition, image guided radiotherapy (IGRT) or surgery is allowed and your doctor will explain the benefits and risks of this type of therapy.

During the study, the study team will:

  • take blood and urine samples.
  • measure PSA and testosterone levels in the blood samples
  • do physical examinations
  • check the participants' overall health
  • examine heart health using electrocardiogram (ECG)
  • check vital signs
  • check cancer status using PSMA PET/CT scans, CT, MRI and bone scans
  • take tumor samples (if required)
  • ask the participants if they have medical problems

About 30 days after the participants have taken their last treatment, the study doctors and their team will check the participants' health and if their cancer worsened. The study team will continue to check this and regularly ask the participants questions about medical problems and subsequent therapies until they leave the study for any reason or until they leave the study for any reason or until the end of the study, whatever comes first.

Official Title

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


Biochemically Recurrent Prostate Cancer, darolutamide, high risk BCR, PSMA PET imaging, Prostatic Neoplasms, Darolutamide (BAY1841788, Nubeqa), ADT, Darolutamide+ADT


You can join if…

Open to males ages 18 years and up

  • 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 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) ≥1.5x109/L (participant must not have received any growth factor within 4 weeks prior to sample being taken); Platelet count ≥100x109/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 m2 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.

You CAN'T join if...

  • 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.


  • University of California Irvine Medical Center not yet accepting patients
    Orange California 92868-3201 United States
  • University of California, Los Angeles not yet accepting patients
    Los Angeles California 90095 United States


accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
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Phase 3 research study
Study Type
Expecting 750 study participants
Last Updated