Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorErasmus Medical Center
About this trial
Taxane efficacy in metastatic prostate cancer is modest due to resistance development. Several clinical phase III studies in metastatic castration-naïve prostate cancer (mCNPC) patients have shown that adding an androgen receptor signalling inhibitor (ARSi) to patients receiving a taxane and androgen deprivation therapy (ADT) improves survival endpoints. Adding ARSi darolutamide to docetaxel+ADT in mCNPC patients resulted in a robust OS benefit (HR 0.68). Importantly, the combination of a taxane and darolutamide is not prone to a drug-drug interaction, while there is a detrimental CYP3A4 inducing effect in the case of enzalutamide, resulting in a significant and clinically relevant reduction of cabazitaxel plasma concentrations. The investigators have previously reported preclinical data showing that addition of an androgen receptor signaling inhibitor (ARSi) improves cabazitaxel efficacy, even in metastatic castration-resistant prostate cancer (mCRPC). As treatment options for mCRPC) patients are scarce and patients often develop drug resistance relatively early, a new treatment regimen for this population to delay drug resistance is highly desired. The investigators propose a randomized phase II trial to investigate the efficacy of docetaxel or cabazitaxel plus darolutamide compared to docetaxel or cabazitaxel monotherapy in men with metastatic CRPC, who have progressed on an ARSI.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years;
A confirmed diagnosis of progressive mCRPC (progression according to Prostate cancer Working Group (PCWG) 3 criteria, castration defined as castrate levels of testosterone of <0.5 ng/mL) with an indication for docetaxel or cabazitaxel.
Patients should have had disease progression previously on at least one ARSi (abiraterone, apalutamide, darolutamide or enzalutamide). ARSi administration is allowed both in the mCNPC and in the mCRPC setting. Previous co-administration of docetaxel in mCNPC (triplet-therapy) is allowed, if patients will receive cabazitaxel in this study.
WHO performance ≤ 2
Disqualifiers
Impossibility or unwillingness to take oral drugs
Hypersensitivity to taxanes
Known serious illness or medical unstable conditions that could interfere with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or herpes zoster, organ transplants, kidney failure, serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases)
Symptomatic peripheral neuropathy CTCAE grade ≥2
Trial design
Design model
Parallel
Treatments tested in this trial
Darolutamide
DrugDarolutamide 600 mg b.i.d. until the end of the last taxane cycle
Docetaxel or cabazitaxel
DrugDocetaxel or cabazitaxel Q3W
Treatment groups
245 Participants
are divided into 2 treatment groupsGroup A: Docetaxel or cabazitaxel (SOC)Active comparator 1 intervention
Group B: Docetaxel or cabazitaxel with darolutamideExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Progression free survival
progression free survival, which is defined as time from randomization to radiologic, biochemical or pain progression or death from any cause, whichever occurs first, according to PCWG3
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came firstSecondary outcomes
1
Overall survival
Overall survival, defined as time from randomization to death from any cause.
Time frame
From date of randomization until the date of death from any cause2
Time to progression
Time to progression, defined as time from randomization to radiologic, biochemical or pain progression, whichever occurs first.
Time frame
From date of randomization until the date of first documented progression3
Time to PSA progression
Time to PSA progression, defined as time from randomization to biochemical progression.
Time frame
From date of randomization until the date of first documented PSA progressionSponsors and contacts
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Source ClinicalTrials.gov