Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorSwiss Cancer Institute
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Darolutamide
DrugDarolutamide will be supplied in bottles as 300 mg film-coated tablets for oral intake
Standard of care
Other intervention* 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.
Treatment groups
162 Participants
are divided into 2 treatment groupsGroup A: Arm A: ExperimentalExperimental treatment 1 intervention
Group B: Arm B: ControlOther 1 intervention
Trial outcomes
Primary outcomes
1
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.Secondary outcomes
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.
Time frame
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)
Time frame
From date of randomization until the date of symptomatic/clinical progression, assessed up to 2 years after end of treatment3
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:
Time frame
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
Time frame
From date of randomization until the date of the event of interest, assessed up to 2 years after end of treatment.Sponsors and contacts
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Source ClinicalTrials.gov