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Metastatic Castration-resistant Prostate CancerPhase 2NCT06401980

Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

A Phase 2 study testing Darolutamide in people with Metastatic Castration-resistant Prostate Cancer, run by Swiss Cancer Institute at 13 sites in Switzerland.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Darolutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
13 sitesSwitzerland
Study dates
22 Oct 2024to Sep 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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.
  • Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), ALT and AST ≤ 2.5 x ULN, or ≤ 5 x ULN under the assumption that abnormal values are a result of cancer
  • Adequate renal function: estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 (according to CKD-EPI formula)
  • Men agree not to donate sperm or to father a child during trial treatment and until 3 months after the last dose of trial treatment
  • Patients are able and willing to swallow darolutamide as whole tablet.

Who cannot join

  • 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
Show all 13Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Stefanie Röthlisberger Röthlisberger, PhD contact

+41 31 389 91 91

trials@swisscancerinstitute.ch

13 sites in 1 country

Switzerland13 sites, 12 recruiting
  • Tumorzentrum Aarau TZA

    Aarau, 5000

    Konstantinos Tyriakidis, MD, +41 62 836 78 30, konstantinos.tyriakidis@tumor-zentrum.ch

    Konstantinos Tyriakidis, MD

    Recruiting
  • Kantonsspital Baden

    Baden, 5404

    Andreas Erdmann, MD, +41 56 486 27 62, andreas.erdmann@ksb.ch

    Andreas Erdmann, MD

    Recruiting
  • Istituto Oncologico della Svizzera Italiana (IOSI)

    Bellinzona, 6500

    Ursula Vogl, MD, +41 91 811 84 63, ursula.vogl@eoc.ch

    Ursula Vogl, MD

    Recruiting
  • Inselspital

    Bern

    Dilara Akhoundova, MD, +41 31 63 2 03 91, dilara.akhoundovasanoyan@insel.ch

    Dilara Akhoundova Dilara Akhoundova, MD

    Recruiting
  • Kantonsspital Graubuenden

    Chur, 7000

    Richard Cathomas, MD, 41-81-256-6695, richard.cathomas@ksgr.ch

    Richard Cathomas, MD

    Recruiting
  • Hôpitaux Universitaires Genève HUG

    Geneva, 1211

    Petros Tsantoulis, MD, +41 79 553 23 53, petros.tsantoulis@hcuge.ch

    Petros Tsantoulis, MD

    Recruiting
  • Centre Hospitalier Universitaire Vaudois CHUV

    Lausanne, CH-1011

    Dominik Berthold, MD, +41 21 314 80 83, dominik.berthold@chuv.ch

    Dominik Berthold, MD

    Recruiting
  • Luzerner Kantonsspital

    Lucerne, 6004

    Christian Rothermundt, MD, +41 41 205 58 60, christian.rothermundt@luks.ch

    Christian Rothermundt, MD

    Recruiting
  • Kantonsspital St. Gallen

    Sankt Gallen

    Stefanie Fischer, MD, +41 71 494 11 11, stefanie.fischer@kssg.ch

    Stefanie Fischer, MD

    Recruiting
  • Kantonsspital Winterthur

    Winterthur, 8401

    Lena Züllig, MD, +41 52 266 40 89, lena.zuellig@ksw.ch

    Lena Züllig, MD

    Recruiting
  • OnkoZentrum Zürich - Standort Seefeld

    Zurich, 8038

    Terminated
  • Stadtspital Triemli Zürich

    Zurich, 8063

    Katharina Hoppe, MD, +41 44 416 34 91, katharina.hoppe@stadtspital.ch

    Katharina Hoppe, MD

    Recruiting
  • UniversitaetsSpital Zuerich

    Zurich, 8091

    Anja Lorch, Prof, +41 44 255 22 14, anja.lorch@usz.ch

    Anja Lorch, Prof

    Recruiting

Other trials in Switzerland

About this study

Official title: Addition of Darolutamide to First Line Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC): a Randomized Open Label Phase II Trial

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.

Read the detailed description

Metastatic prostate cancer remains incurable despite several major improvements in the treatment. In the case of pretreated metastatic castration-resistant disease (mCRPC) the options remain scarce and there is still an unmet need in this patient population.

For the majority of patients with metastatic hormone-sensitive prostate cancer (mHSPC) the combination of androgen deprivation (ADT) and ARPI (or even a triplet treatment with ADT, docetaxel and darolutamide or abiraterone) has become standard of care. However, when patients become metastatic castration resistant (mCRPC) over time a change of systemic treatment is necessary and thus this paradigm switch in treatment of mHSPC has had a major impact on treatment of mCRPC patients. Many patients developing metastatic castration-resistant disease these days have not only received ADT but also an ARPI and, in some cases, also docetaxel. Therefore, the treatment options in the first line setting of mCRPC are restricted and the outcome is poorer compared to the past. Improvement of first line mCRPC is an important unmet clinical need.

The SAKK has demonstrated in two earlier studies that maintenance treatment with an ARPI (orteronel in SAKK 08/11 or darolutamide in SAKK 08/16) can improve radiographic progression-free survival in pretreated mCRPC patients after ARPI and/or taxane based. This maintenance concept could be introduced more generally in the first line setting of mCRPC.

In the SAKK 08/16 trial, darolutamide maintenance was shown to prolong progression-free survival (PFS) compared to placebo, in patients with mCRPC who had received prior ARPI, and whose disease did not progress during taxane therapy. This benefit was more pronounced in patients with prior response to ARPI.

Taken together it is hypothesized that the continued AR-pathway blockade with darolutamide in patients progressing from mHSPC to mCRPC on ARPI treatment can improve outcome when it is added to a standard first line mCRPC therapy and then continued as maintenance. SAKK proposes to add the ARPI darolutamide to standard first line mCRPC treatment consisting of either taxane chemotherapy (docetaxel or cabazitaxel), olaparib, radium 223 or LuPSMA. The choice of standard of care treatment is up to the investigator, respecting the country specific approvals. Darolutamide will be given concomitantly with the chosen first line treatment and will be continued as maintenance afterwards until radiographic progression.

Being tested
Darolutamide, Standard of care
Keywords
Metastatic Castration-Resistant Prostate Cancer, mCRPC, Darolutamide, phase II trial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarolutamideDrug

    Also called Nubeqa®

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

  • Standard of careOther

    • 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.

Study groups in NCT06401980
Study groupRoleWhat they receive
Arm A: ExperimentalExperimentalStandard of Care + Darolutamide 2 x 600 mg BID until radiographic PD
Receives: Drug: Darolutamide
Arm B: ControlOtherStandard of Care
Receives: Other: Standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Radiographic progression-free survival (rPFS)

    Measured: 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)
  1. Overall survival (OS)

    OS is defined as the time from randomization until death due to any cause. Patients not experiencing an event (death) will be censored at the last date they were known to be alive.

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

  2. Time to symptomatic/clinical progression

    Time to symptomatic/clinical progression is defined as the time from randomization to the time point of symptomatic/clinical progression. Patients not experiencing an event will be censored at the date of the last visit before initiation of a new anti-cancer treatment, if any.

    Symptomatic/clinical progression is defined by one of the following:

    • Occurrence of a SRE due to bone metastases, defined as pathologic fracture, spinal cord compression, palliative radiation to bone, or surgery to bone
    • Treating physician decides for intervention due to new disease related complications (e.g., urinary obstruction, hydronephrosis)

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

  3. Time to PSA progression

    Time to PSA progression is defined as the time from randomization to the time point of PSA progression. Patients not experiencing an event will be censored at the date of the last available PSA assessment before initiation of a new anti-cancer treatment, if any. PSA progression is defined as:

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

  4. Event-free survival (EFS)

    Event-free survival is defined as the time from randomization until the event of interest. Patients not experiencing an event will be censored at the date of the last available assessment before initiation of a new anti-cancer treatment, if any

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

  5. Objective response rate according to RECIST

    Objective response is defined as any complete response (CR) or partial response (PR) according to RECIST 1.1 criteria (Appendix 1) achieved during treatment. Any patient with CR or PR as best observed response during treatment will be considered as a success; otherwise they will be considered as a failure.

    Patients without any tumor assessment or with non-evaluable response (NE) during treatment will be considered as failures for this endpoint.

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

  6. PSA response (30%, 50%, 90% and best)

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

  7. Duration of PSA response (50%)

    Duration of PSA response is defined as the time from appearance of 50% PSA response during treatment to the time point of PSA progression. Definition of PSA progression is provided above. In case the patient does not experience PSA progression, the patient will be censored at the last PSA assessment before starting a new anti-cancer treatment, if any.

    This endpoint will be calculated for the subgroup of patients achieving 50% PSA response.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2024
  2. Study start22 Oct 2024
  3. Primary completionJun 2030 (estimated)
  4. Study completionSep 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
International, randomized, open label, phase II study.
Masking
None (open label)
Enrolment
162 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06401980
Sponsor's protocol ID
SAKK 08/23
Status last verified
Oct 2026
First submitted
2 May 2024
Last updated
9 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Darolutamide in people with Metastatic Castration-resistant Prostate Cancer, run by Swiss Cancer Institute at 13 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Stefanie Röthlisberger Röthlisberger, PhD (+41 31 389 91 91, trials@swisscancerinstitute.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic progression-free survival (rPFS) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.

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