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

October 16, 2023 updated by: Prof. R.H.J. Mathijssen, MD, PhD, Erasmus Medical Center

A Randomized Phase II Trial of Docetaxel or Cabazitaxel With or Without Darolutamide in Men With Metastatic Castration-resistant Prostate Cancer

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

245

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Docetaxel or cabazitaxel (SOC)
Drug: Docetaxel or cabazitaxel
Docetaxel or cabazitaxel Q3W
Experimental: Docetaxel or cabazitaxel with darolutamide
Drug: Docetaxel or cabazitaxel
Docetaxel or cabazitaxel Q3W
Drug: Darolutamide
Darolutamide 600 mg b.i.d. until the end of the last taxane cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 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
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of randomization until the date of death from any cause
Overall survival, defined as time from randomization to death from any cause.
From date of randomization until the date of death from any cause
Time to progression
Time Frame: 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.
From date of randomization until the date of first documented progression
Time to PSA progression
Time Frame: From date of randomization until the date of first documented PSA progression
Time to PSA progression, defined as time from randomization to biochemical progression.
From date of randomization until the date of first documented PSA progression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erasmus Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 19, 2023

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

February 17, 2023

First Submitted That Met QC Criteria

February 28, 2023

First Posted (Actual)

March 9, 2023

Study Record Updates

Last Update Posted (Actual)

October 18, 2023

Last Update Submitted That Met QC Criteria

October 16, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL83539.078.23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Castration-resistant Prostate Cancer

Clinical Trials on Docetaxel or cabazitaxel

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cameroon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe