Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC

Phase 2

Recruiting

• Conditions: Metastatic Castration-resistant Prostate Cancer
• Interventions: Drug: Docetaxel or cabazitaxel; Drug: Darolutamide

• Registration Number: NCT05762536
• Lead Sponsor: Erasmus Medical Center

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-17
• Study First Submitted QC: 2023-02-28
• Study First Posted: 2023-03-09
• Study Start: 2023-11-29
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-27
• Primary Completion: 2027-05
• Study Completion: 2028-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 245

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Docetaxel or cabazitaxel (SOC)	Docetaxel or cabazitaxel	-
Docetaxel or cabazitaxel with darolutamide	Darolutamide	-
Docetaxel or cabazitaxel with darolutamide	Docetaxel or cabazitaxel	-

Primary Outcome Measures

Name	Time	Method
Progression free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first	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

Secondary Outcome Measures

Name	Time	Method
Time to PSA progression	From date of randomization until the date of first documented PSA progression	Time to PSA progression, defined as time from randomization to biochemical progression.
Time to progression	From date of randomization until the date of first documented progression	Time to progression, defined as time from randomization to radiologic, biochemical or pain progression, whichever occurs first.
Overall survival	From date of randomization until the date of death from any cause	Overall survival, defined as time from randomization to death from any cause.

Trial Locations

Locations (1)

Erasmus MC Cancer Institute; 🇳🇱 Rotterdam, Netherlands