Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC

NCT ID: NCT05762536

Last Updated: 2024-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 245 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-29
• Study Completion Date: 2028-05-31

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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel or cabazitaxel (SOC)

Group Type: ACTIVE_COMPARATOR

Docetaxel or cabazitaxel

Intervention Type: DRUG

Docetaxel or cabazitaxel Q3W

Docetaxel or cabazitaxel with darolutamide

Group Type: EXPERIMENTAL

Darolutamide

Intervention Type: DRUG

Darolutamide 600 mg b.i.d. until the end of the last taxane cycle

Docetaxel or cabazitaxel

Intervention Type: DRUG

Docetaxel or cabazitaxel Q3W

Interventions

Darolutamide

Darolutamide 600 mg b.i.d. until the end of the last taxane cycle

Intervention Type: DRUG

Docetaxel or cabazitaxel

Docetaxel or cabazitaxel Q3W

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Prof. R.H.J. Mathijssen, MD, PhD

Prof. dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Erasmus MC Cancer Institute

Rotterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Tanja van Dijk

Role: CONTACT

interne.oncologie@erasmusmc.nl

0031107040704

Facility Contacts

Tanja van Dijk, MD

Role: primary

interne.oncologie@erasmusmc.nl

0031107040704

Other Identifiers

NL83539.078.23

Identifier Type: -

Identifier Source: org_study_id