Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC

NCT05762536 | Recruiting Phase 2

• 1 other identifier: NL83539.078.23
• Study Type: interventional
• Target: 245
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  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

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

Secondary Outcomes (3)

• Overall survival

  From date of randomization until the date of death from any cause

• Time to progression

  From date of randomization until the date of first documented progression

• Time to PSA progression

  From date of randomization until the date of first documented PSA progression

Study Arms (2)

Docetaxel or cabazitaxel (SOC)

ACTIVE COMPARATOR

Drug: Docetaxel or cabazitaxel

Docetaxel or cabazitaxel with darolutamide

EXPERIMENTAL

Drug: Darolutamide; Drug: Docetaxel or cabazitaxel

Interventions

Darolutamide DRUG

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

Docetaxel or cabazitaxel with darolutamide

Docetaxel or cabazitaxel DRUG

Docetaxel or cabazitaxel Q3W

Docetaxel or cabazitaxel (SOC); Docetaxel or cabazitaxel with darolutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC Cancer Institute

Rotterdam, 3015GD, Netherlands

RECRUITING

MeSH Terms

Interventions

darolutamide; Docetaxel; cabazitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Tanja van Dijk

CONTACT

0031107040704; interne.oncologie@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: March 9, 2023
• Study Start: November 29, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)