Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

NCT06401980 | Recruiting Phase 2 DMC

• 1 other identifier: SAKK 08/23
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 13

Brief Summary

Despite improvements in treatment, metastatic prostate cancer remains incurable, especially in the case of pretreated metastatic castration-resistant disease (mCRPC), where treatment options are limited, leading to an unmet need. The paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has affected the treatment landscape for mCRPC patients. Many have already received androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI), making first-line mCRPC treatment challenging. The Swiss Group for Clinical Cancer Research (SAKK) has shown in previous studies that maintenance treatment with an ARPI, such as darolutamide, can improve radiographic progression-free survival (rPFS) in pretreated mCRPC patients. In the SAKK 08/16 trial, darolutamide maintenance was found to prolong PFS compared to placebo, especially in patients who responded well to prior ARPI treatment. Based on these findings, the hypothesis is that continued AR-pathway blockade with darolutamide, initiated in patients progressing from mHSPC to mCRPC on ARPI treatment, can improve outcomes when added to standard first-line mCRPC therapy and continued as maintenance. The proposed study aims to evaluate the efficacy of darolutamide, combined with physician-choice standard of care (including taxane chemotherapy, olaparib, radium 223, or LuPSMA), followed by maintenance therapy, on rPFS for patients in the first-line setting of mCRPC.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Metastatic Castration-Resistant Prostate Cancer; mCRPC; Darolutamide; phase II trial

Outcome Measures

Primary Outcomes (1)

• Radiographic progression-free survival (rPFS)

  From the date of randomization until the date of radiographic disease progression or death from any cause, assessed up to 2 years after end of treatment.

Secondary Outcomes (7)

• Overall survival (OS)

  From the date of randomization until the date of death from any cause, assessed up to 2 years after end of treatment.

• Time to symptomatic/clinical progression

  From date of randomization until the date of symptomatic/clinical progression, assessed up to 2 years after end of treatment

• Time to PSA progression

  From date of randomization until the date of PSA progression, assessed up to 2 years after end of treatment.

• Event-free survival (EFS)

  From date of randomization until the date of the event of interest, assessed up to 2 years after end of treatment.

• Objective response rate according to RECIST

  From the date of randomization until date of the end of treatment, estimated up to 2 years after registration

Study Arms (2)

Arm A: Experimental

EXPERIMENTAL

Standard of Care \+ Darolutamide 2 x 600 mg BID until radiographic PD

Drug: Darolutamide

Arm B: Control

OTHER

Standard of Care

Other: Standard of care

Interventions

Darolutamide DRUG

Darolutamide will be supplied in bottles as 300 mg film-coated tablets for oral intake

Also known as: Nubeqa®

Arm A: Experimental

Standard of care OTHER

* Docetaxel * Cabazitaxel * LuPSMA * Radium 223 * Olaparib, in case of BRCA1 or 2 mutated or HRR deficient tumors The standard of care is chosen by the local investigator and respecting the country specific approvals.

Arm B: Control

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to Swiss law and ICH GCP E6(R2) regulations before registration and prior to any trial specific procedures
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate
• Castration resistance: tumor progression after orchiectomy or during treatment with GnRH analogues (agonists or antagonists).
• Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or antagonists) during the trial
• Metastatic disease, documented by imaging according to PCWG3 criteria
• Measurable disease or bone lesions that are evaluable according to PCWG3 criteria
• A minimum of 12 months on ADT+ARPI therapy (calculated from ADT initiation) within mHSPC setting, showing an at least 50% PSA response or partial remission according to RECIST v1.1. ARPI change within mHSPC is only allowed for intolerance.
• Progressive disease according to modified PCWG3 before registration is defined as (at least 2 out of 3):
• PSA progression ≥ 25% above nadir (2 consecutive rises at least 3 weeks apart)
• New metastatic lesion on imaging (at least two or more new bone lesions on bone scan or one new non-bone lesion or progression on PSMA-PET/CT according to PROMISE V2 criteria
• Clinical progression
• Patients with a previously treated malignancy are eligible, when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low
• Age ≥ 18 years
• WHO performance status 0-2
• Adequate bone marrow function: absolute neutrophil count ≥ 1.0 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90 g/L.

You may not qualify if:

• Presence of a small cell component
• Prior systemic therapy for metastatic castration-resistant disease
• Prior chemotherapy for mHSPC, except docetaxel
• Prior LuPSMA or radium 223 for prostate cancer
• Concomitant or recent (within 28 days of registration) treatment with any other experimental drug
• Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control and GnRH analogues
• Severe or uncontrolled cardiovascular disease
• Acute exacerbations of chronic illnesses, serious infections, or major surgery within 28 days before expected start of treatment
• Clinical or radiological evidence of current spinal cord compression
• Any concomitant drugs contraindicated for use with darolutamide according to the approved product information
• Known hypersensitivity to darolutamide
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of darolutamide
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (13)

Tumorzentrum Aarau TZA

Aarau, 5000, Switzerland

RECRUITING

Kantonsspital Baden

Baden, 5404, Switzerland

RECRUITING

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, 6500, Switzerland

RECRUITING

Inselspital

Bern, Switzerland

RECRUITING

Kantonsspital Graubuenden

Chur, 7000, Switzerland

RECRUITING

Hôpitaux Universitaires Genève HUG

Geneva, 1211, Switzerland

RECRUITING

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, CH-1011, Switzerland

RECRUITING

Luzerner Kantonsspital

Lucerne, 6004, Switzerland

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

RECRUITING

OnkoZentrum Zürich - Standort Seefeld

Zurich, 8038, Switzerland

TERMINATED

Stadtspital Triemli Zürich

Zurich, 8063, Switzerland

RECRUITING

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Interventions

darolutamide; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Richard Cathomas, Prof

  Kantonsspital Graubünden

  STUDY CHAIR

• Ursula Vogl, MD

  Istituto Oncologico della Svizzera Italiana

  STUDY CHAIR

Central Study Contacts

Stefanie Röthlisberger Röthlisberger, PhD

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Study Design

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

Model Details: International, randomized, open label, phase II study.

Study Record Dates

• First Submitted: May 2, 2024
• First Posted: May 7, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (13)