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

NCT05826509 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 22GENH03
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 19

Brief Summary

This is a phase II, multicenter, randomized open-label and comparative trial designed to study the effectiveness and the safety of androgen receptor antagonist (darolutamide) combined with surgery in patients with high-risk and/or locally advanced prostate cancer. In this trial, patients will be assigned in one of the two following treatments arms:

• Arm A (control arm): Surgery alone (radical prostatectomy with lymph node dissection)
• Arm B (experimental arm): Peri-operative darolutamide + surgery (radical prostatectomy with lymph node dissection) A total of 240 patients will have to be randomized with 120 patients in the control arm and 120 patients in the experimental arm.

Conditions

Prostate Cancer

Keywords

Prostate cancer; Hight risk; Locally advanced; Radical prostatectomy; ADT sparing; Darolutamide

Outcome Measures

Primary Outcomes (1)

• The non-curable progression-free survival (NC-PFS) defined as the time from randomization to non-curable event.

  5 years for each patient

Secondary Outcomes (9)

• Metastatic-Free Survival (MFS) defined as the time from randomization to the appearance of distant metastasis or death from any cause.

  5 years for each patient

• PSA-RFS (Recurrence-Free survival) defined as the time from randomization to PSA recurrence according to the European Association of Urology (EAU) criteria or death from any cause.

  5 years for each patient

• Overall Survival (OS) defined as the time from randomization to death from any cause.

  5 years for each patient

• pathological Complete Response (pCR) rate defined as the number of patients presenting a pathological complete response (i.e., absence of residual tumor found in the surgery specimens) divided by the number of patients in the experimental arm.

  5 years for each patient

• Safety assessed using the NCI-CTCAE Version 5.0.

  3 years for each patient

Study Arms (2)

Control arm

ACTIVE COMPARATOR

Other: Surgery alone

Experimental arm

EXPERIMENTAL

Drug: Peri-operative darolutamide + surgery.

Interventions

Surgery alone OTHER

Radical prostatectomy with lymph node dissection will be performed.

Control arm

Peri-operative darolutamide + surgery. DRUG

Darolutamide: 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg; for a total duration of 9 months. Darolutamide will start at day 1. Surgery: radical prostatectomy with lymph node dissection will be performed after at least 3 months of darolutamide treatment.

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histologically confirmed adenocarcinoma of the prostate
• 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
• No distant metastasis confirmed by imaging (i.e., MRI/CT-Scan and Bone Scintigraphy or PET-Scan)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1
• Patient eligible for radical prostatectomy as per the investigator
• Adequate organ function within 28 days prior to start of treatment determined by the following central laboratory values:

You may not qualify if:

• Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
• Prior treatment for prostate cancer
• Castrated men (Bilateral orchiectomy or other)
• History of any pelvic radiation
• 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
• 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
• Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
• Gastrointestinal conditions affecting absorption
• Known or suspected contraindications or hypersensitivity to darolutamide
• 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
• Major surgery within 28 days before first dose of study treatment
• 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
• Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
• Concurrent enrolment in another interventional therapeutic clinical study.

Sponsors & Collaborators

• Institut Claudius Regaud: lead
• Bayer: collaborator

Study Sites (19)

Chu Angers

Angers, France

Location

CHU Bordeaux

Bordeaux, France

Location

Institut Bergonié

Bordeaux, France

Location

Chu Henri Mondor

Créteil, France

Location

CHU Grenoble

Grenoble, France

Location

Hopital Claude Huriez

Lille, France

Location

CHU Lyon - Hôpital Edouard Herriot

Lyon, France

Location

Institut Paoli-Calmettes

Marseille, France

Location

Hopital Paris Saint-Joseph

Paris, 75014, France

Location

Hopital Europeen Georges-Pompidou

Paris, France

Location

Hopital Pitie Salpetriere

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

CHU Lyon - Sud

Pierre-Bénite, France

Location

Clinique La Croix Du Sud

Quint-Fonsegrives, France

Location

CHU Rennes

Rennes, France

Location

Hopital Foch

Suresnes, France

Location

CHU Toulouse

Toulouse, France

Location

Institut Universitaire Du Cancer Toulouse - Oncopole

Toulouse, France

Location

Chu Tours - Hopital Bretonneau

Tours, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: April 24, 2023
• Study Start: August 10, 2023
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: March 27, 2026

Record last verified: 2026-01

Locations

FR (19)