Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC (DAROTAXEL)

Erasmus University

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Docetaxel or cabazitaxel; Drug: Darolutamide

Study type: Interventional

Funder types: Other

Identifiers

NCT05762536

NL83539.078.23

Details and patient eligibility

About

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.

Enrollment: 245 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years;
2. 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.
3. 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.
4. WHO performance ≤ 2
5. Able and willing to sign the Informed Consent Form prior to screening evaluations
6. Adequate haematological, renal and liver function and chemistry.

Exclusion criteria

1. Impossibility or unwillingness to take oral drugs
2. Hypersensitivity to taxanes
3. 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)
4. Symptomatic peripheral neuropathy CTCAE grade ≥2
5. Docetaxel-rechallenge.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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245 participants in 2 patient groups

Docetaxel or cabazitaxel (SOC)

Active Comparator group

Treatment:

Drug: Docetaxel or cabazitaxel

Docetaxel or cabazitaxel with darolutamide

Experimental group

Treatment:

Drug: Darolutamide

Drug: Docetaxel or cabazitaxel