A Randomized Phase II Trial of Docetaxel or Cabazitaxel With or Without Darolutamide in Men With Metastatic Castration-resistant Prostate Cancer

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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
Participation Requirements
Sex: Male
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

• Able and willing to sign the Informed Consent Form prior to screening evaluations

• Adequate haematological, renal and liver function and chemistry.

Locations
Other Locations
Netherlands
Erasmus MC Cancer Institute
RECRUITING
Rotterdam
Contact Information
Primary
Tanja van Dijk
interne.oncologie@erasmusmc.nl
0031107040704
Time Frame
Start Date: 2023-11-29
Estimated Completion Date: 2028-05
Participants
Target number of participants: 245
Treatments
Active_comparator: Docetaxel or cabazitaxel (SOC)
Experimental: Docetaxel or cabazitaxel with darolutamide
Related Therapeutic Areas
Sponsors
Leads: Erasmus Medical Center

This content was sourced from clinicaltrials.gov

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