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Surgery with or without darolutamide for high-risk prostate cancer

SUrGery With or Without dARolutamide in High-risk and/or Locally Advanced Prostate Cancer

Phase 2 Interventional Institut Claudius Regaud · NCT05826509

This study is testing if adding a medication called darolutamide to surgery can help men with high-risk prostate cancer do better than surgery alone.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment240 (estimated)
Ages18 Years and up
SexMale
SponsorInstitut Claudius Regaud Academic / other
Drugs / interventionsradiation
Locations17 sites (Angers and 16 other locations)
Trial IDNCT05826509 on ClinicalTrials.gov

What this trial studies

This phase II, multicenter, randomized open-label trial aims to evaluate the effectiveness and safety of the androgen receptor antagonist darolutamide when combined with surgery in patients diagnosed with high-risk and/or locally advanced prostate cancer. Participants will be randomly assigned to receive either surgery alone or surgery with peri-operative darolutamide. A total of 240 patients will be enrolled, with 120 in each treatment arm, to assess the potential benefits of adding darolutamide to the surgical approach.

Who should consider this trial

Good fit: Ideal candidates for this study are adult males aged 18 and older with histologically confirmed high-risk or locally advanced prostate cancer.

Not a fit: Patients with distant metastasis or those not eligible for radical prostatectomy will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment outcomes for patients with high-risk prostate cancer by potentially enhancing the effectiveness of surgical intervention.

How similar studies have performed: Other studies have shown promise in using androgen receptor antagonists in combination with surgery, suggesting a potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Age ≥18 years
2. Histologically confirmed adenocarcinoma of the prostate
3. High-risk and/or locally advanced prostate cancer diagnosis defined by:

   One of the following criteria is sufficient to define a high-risk and/or locally advanced prostate cancer:
   * ISUP grade 4 or 5 on biopsies
   * cN1 disease in MRI or PET-Scan
   * T3b disease in MRI

   If these criteria are not being identified, two of the following criteria are necessary to define high-risk and/or locally advanced prostate cancer:
   * PSA value \>20 ng/ml
   * ≥ 50% of the core of biopsies need to be positive for adenocarcinoma ISUP grade 3
   * T3a disease in MRI
4. No distant metastasis confirmed by imaging (i.e., MRI/CT-Scan and Bone Scintigraphy or PET-Scan)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1
6. Patient eligible for radical prostatectomy as per the investigator
7. Adequate organ function within 28 days prior to start of treatment determined by the following central laboratory values:

   * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin less than the upper limit of normal (ULN; note that in subjects with Gilbert's syndrome, if total bilirubin is \>1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may be eligible);
   * Serum creatinine \<1.5 mg/dL;
   * Platelets ≥75,000/uL, without transfusion and/or growth factors within 1 month prior to randomization;
   * Hemoglobin \>12.0 g/dL (7.4 mmol), without transfusion and/or growth factors within 1 month prior to randomization;
   * Adequate renal function: creatinine clearance/eGFR within normal limits to baseline assessed as per local standard method;
   * Normal cardiac function according to local standard by 12-lead Electrocardiogram (ECG) (complete, standardized 12-lead recording).
8. Patient able to receive darolutamide for up to 9 months as per the investigator
9. Patient able to swallow whole study drug tablets
10. Life expectancy more than 5 years
11. Men engaged in sexual activity with a woman of childbearing potential should accept (or female partners of men enrolled in the study who are of childbearing potential or are pregnant) to use an highly effective contraception during darolutamide treatment and at least one week after the end of the investigational product
12. Signed informed consent
13. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up
14. Patient affiliated to a Social Health Insurance in France.

Exclusion Criteria:

1. Distant metastasis (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.
2. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
3. Prior treatment for prostate cancer
4. Castrated men (Bilateral orchiectomy or other)
5. History of any pelvic radiation
6. Any of the following concurrent illness within 6 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
7. Uncontrolled hypertension as indicated by a systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg at screening despite medical management. Participants with hypertension can enroll provided BP is stable and controlled by anti-hypertensive treatment
8. HIV-positive patient with one or more of the following: Not receiving highly active antiretroviral therapy; Had a change in antiretroviral therapy within 6 months of the start of screening; Receiving antiretroviral therapy that may interfere with study drug; CD4 count \<350 at screening; AIDS-defining opportunistic infection within 6 months of start of screening
9. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
10. Gastrointestinal conditions affecting absorption
11. Known or suspected contraindications or hypersensitivity to darolutamide
12. Treatment with strong CYP3A4 inducers and P-gp inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug
13. Major surgery within 28 days before first dose of study treatment
14. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
15. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
16. Concurrent enrolment in another interventional therapeutic clinical study.
17. Patients with a history of another malignancy at high risk of recurrence within 5 years and with a concurrent malignancy requiring active treatment or having required anticancer treatment within 6 months prior to inclusion.

Where this trial is running

Angers and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Prostate CancerProstate cancerHight riskLocally advancedRadical prostatectomyADT sparingDarolutamide
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.