Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC

About This Trial

This clinical trial is testing whether adding a hormone-blocking pill called darolutamide to standard chemotherapy helps fight advanced prostate cancer better than chemotherapy alone.
It is open to adults with prostate cancer that has spread to other parts of the body and has continued to grow despite earlier hormone therapies.
If you join, you will be randomly chosen to receive standard chemotherapy either by itself or combined with the study pills.
Before deciding, you should know that you must have reasonably good liver and kidney function, be able to swallow pills, and not have severe nerve numbness or serious allergies to chemotherapy drugs.

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.

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This clinical trial is testing whether adding a hormone-blocking pill called darolutamide to standard chemotherapy helps fight advanced prostate cancer better than chemotherapy alone.

Full Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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
Docetaxel-rechallenge.