A Trial Comparing Docetaxel 75 mg/m2 (3w) Versus Docetaxel 50 mg/m2 (2w) in Combination With Darolutamide + ADT in mHSPC Patients (ARASAFE)

February 28, 2024 updated by: Marc-Oliver Grimm, Jena University Hospital

A Randomised, Phase 3 Trial Comparing 3-weekly Docetaxel 75 mg/m2 (in a 3 Week Cycle) Versus 2-weekly Docetaxel 50 mg/m2 (in a 4 Week Cycle) in Combination With Darolutamide + ADT in Patients With mHSPC

The purpose of this clinical phase 3 randomized trial is to compare two different dosing schedules of Docetaxel in combination with ADT and Darolutamide in subjects with mHSPC. The main question aims to compare grade 3-5 adverse events (AEs) in patients with mHSPC treated with 6 cycles of either Docetaxel 75 mg/m2 every 3 weeks in a 3 week cycle or 6 cycles of Docetaxel 50 mg/m2 every 2 weeks in a 4 week cycle in combination with Darolutamide + ADT. The primary endpoint are Grade 3-5 AEs, followed by neutropenia grade 3/4 + grade 5 AEs to be analysed 28 weeks after last patient first Docetaxel dose (LPFD).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, open, controlled, multicenter phase III clinical trial. Approximately 250 patients with mHSPC who are candidates for docetaxel, darolutamide and ADT will be randomized (1:1 ratio) to one of the following study arms:

  • Arm 1: 6 x Docetaxel 75 mg/m2 every 3 weeks of a 3 week cycle
  • Arm 2: 6 x Docetaxel 50 mg/ m2 every 2 weeks of a 4 week cycle Subjects will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels.

All subjects must receive ADT of Investigator's choice (LHRH agonist/antagonists or orchiectomy) and darolutamide as standard therapy. Six cycles of docetaxel are be administered after randomization according to either Arm 1 or Arm 2. After completion of study drug treatment, subjects will continue with the observation period. During the observation period all subjects will continue with Darolutamide+ADT until occurrence of metastatic castration-resistant prostate cancer (mCRPC).

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Phase 3

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 Contact Backup

Study Locations

  • Germany
      • Bergisch Gladbach, Germany, 51465
      • Berlin, Germany, 10967
        • Not yet recruiting
        • Vivantes Prostatazentrum im Klinikum am Urban
        • Contact:
          • Jonas Busch, Prof. Dr. med.
        • Contact:
          • Ines Santiago, Dr. med.
      • Bonn, Germany, 53127
        • Active, not recruiting
        • Universitätsklinikum Bonn
      • Braunschweig, Germany, 38100
      • Dessau, Germany, 06847
      • Düsseldorf, Germany, 40225
      • Erfurt, Germany, 99089
      • Erlangen, Germany, 91054
      • Essen, Germany, 45147
      • Essen, Germany, 45136
        • Not yet recruiting
        • KEM | Evang. Kliniken Essen-Mitte
        • Contact:
      • Frankfurt am Main, Germany, 60590
        • Not yet recruiting
        • Universitäts Klinikum Frankfurt
        • Contact:
      • Frankfurt am Main, Germany, 60488
        • Active, not recruiting
        • Krankenhaus Nordwest
      • Giessen, Germany, 35392
        • Recruiting
        • Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen
        • Contact:
          • Florian Wagenlehner, Prof. Dr. med.
        • Contact:
          • Adrian Pilatz, Prof. Dr.
      • Hamburg, Germany
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf
        • Contact:
      • Herne, Germany, 44625
      • Köln, Germany
        • Active, not recruiting
        • UROLOGIE BAYENTHAL Gemeinschaftspraxis
      • Lübeck, Germany
        • Active, not recruiting
        • Universitätsklinikum Schleswig-Holstein - Campus Lübeck
      • Magdeburg, Germany, 39120
      • Mannheim, Germany, 68167
      • Marburg, Germany, 35043
      • München, Germany, 81377
      • München, Germany, 81675
      • Münster, Germany, 48149
      • Nürnberg, Germany, 90419
      • Nürnberg, Germany, 90491
      • Nürtingen, Germany, 72622
      • Trier, Germany, 54292
      • Tuebingen, Germany, 72076
      • Ulm, Germany, 89081
      • Wuppertal, Germany, 42283
      • Würzburg, Germany, 97080
        • Not yet recruiting
        • Uniklinikum Wurzburg
        • Contact:
    • Baden-Württemberg
      • Heidelberg, Baden-Württemberg, Germany, 69120
        • Recruiting
        • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
        • Contact:
          • Christine Barbara Grün, Dr. med.
        • Contact:
          • Stefanie Zschäbitz, Dr. med.
    • Hessen
      • Wetzlar, Hessen, Germany, 35578
        • Active, not recruiting
        • Klinikum Wetzlar
    • München
      • Planegg, München, Germany, 82152
        • Active, not recruiting
        • Urologische Klinik München Planegg
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
        • Not yet recruiting
        • Med. Hochschule Hannover
        • Contact:
          • Philipp Ivanyi, PD Dr. med.
        • Contact:
          • Eggers Hendrik, Dr. med.
    • Nordrhein-Westfalen
      • Duisburg, Nordrhein-Westfalen, Germany, 47169
        • Recruiting
        • Urologicum Duisburg
        • Contact:
          • Eva Hellmis, Dr. med.
        • Contact:
          • Lena Rößing, Dr. med.
      • Paderborn, Nordrhein-Westfalen, Germany, 33098
        • Not yet recruiting
        • Brüderkrankenhaus St- Josef Paderborn
        • Contact:
          • Tobias Gaska, Dr. med.
        • Contact:
          • Harald Müller-Huesmann, Dr. med.
      • Würselen, Nordrhein-Westfalen, Germany, 52146
        • Not yet recruiting
        • Urologisches Zentrum Euregio
        • Contact:
          • Thomas Pulte, Dr. med.
        • Contact:
          • Stefan Wolter, Dr. med.
    • Sachsen-Anhalt
      • Halle/Saale, Sachsen-Anhalt, Germany, 06120
        • Not yet recruiting
        • Krankenhaus Martha-Maria Halle Dölau gGmbH
        • Contact:
          • Florian Seseke, Prof. Dr.
        • Contact:
          • Juliane Künzel, Dr. med.
    • Schleswig Holstein
      • Wilhelmshaven, Schleswig Holstein, Germany, 26389
        • Active, not recruiting
        • Praxisgemeinschaft f. Onkologie & Urologie
    • Thuringia
      • Jena, Thuringia, Germany, 07747
        • Recruiting
        • University Hospital Jena, Department of Urology
        • Principal Investigator:
          • Marc-Oliver Grimm, Prof. Dr.
        • Contact:

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:

  • Written informed consent
  • Males ≥18 years of age
  • Histologically or cytologically confirmed adenocarcinoma of prostate
  • Investigator assessed metastatic disease documented either by a positive bone scan, or for soft tissue or visceral metastases, either by contrast-enhanced abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan assessed. Metastatic disease is defined as either malignant lesions in bone scan or soft tissue/visceral lesions according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Lymph nodes are measurable if the short axis diameter is ≥15 mm, soft tissue/visceral lesions are measurable if the long axis diameter is ≥10 mm.
  • Subjects with lymph node metastases only (either below the aortic bifurcation (N1) or above the aortic bifurcation (M1a)) will not be eligible for the study.
  • Subjects must be candidates for ADT, docetaxel and darolutamide therapy per Investigator's judgment
  • Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but no longer than 12 weeks before randomization. For subjects receiving LHRH agonists, treatment in combination with a first generation anti-androgen for at least 4 weeks, prior to randomization is recommended. First generation anti-androgen has to be stopped prior to randomization.
  • An Eastern Cooperative Oncology Group performance status of 0 or 1
  • Blood counts at Screening: hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5x109/L, platelet count ≥100x109/L (subject must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at Screening)
  • Screening values of serum alanine aminotransferase and/or aspartate transaminase ≤1.5x upper limit of normal (ULN), total bilirubin ≤ULN, creatinine ≤2.0x ULN

Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide and for 3 months after the end of the treatment with darolutamide and 6 months after treatment with docetaxel.

Exclusion Criteria:

  • Exclusion criteria
  • Prior treatment with:
  • LHRH agonist/antagonists started more than 12 weeks before randomization Second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide, other investigational AR inhibitors
  • Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer
  • Chemotherapy, immunotherapy, radium or other therapeutic radiopharmaceuticals for prostate cancer (e.g. Lutetium177-PSMA) prior to randomization
  • Treatment with radiotherapy (external beam radiation therapy, brachytherapy) within 2 weeks before randomization
  • Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
  • Contraindication to both CT and MRI contrast agent
  • Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris,coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
  • Uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite medical management
  • Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed ≥5 years before randomization and from which the subject has been disease-free
  • A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study drug
  • An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need for treatment
  • Previous (within 28 days before the start of study drug or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s)
  • Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results
  • Inability to swallow oral medications
  • Previous assignment to treatment in this study

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1
6 x Docetaxel 75 mg/m2 every 3 weeks of a 3 week cycle Co-administration of docetaxel, darolutamide and standard ADT
Drug: Docetaxel
Docetaxel
Drug: Standard ADT (androgen deprivation therapy)
as prescribed by the treating physician.
Drug: Standard Darolutamide
2x600 mg/d as prescribed by the treating physician
Experimental: Arm 2
6 x Docetaxel 50 mg/ m2 every 2 weeks of a 4 week cycle Co-administration of docetaxel, darolutamide and standard ADT
Drug: Docetaxel
Docetaxel
Drug: Standard ADT (androgen deprivation therapy)
as prescribed by the treating physician.
Drug: Standard Darolutamide
2x600 mg/d as prescribed by the treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of grade 3-5 AEs
Time Frame: 28 weeks after last patient first Docetaxel dose (LPFD)
Rate of grade 3-5 AEs, followed by rate of neutropenia grade 3/4 + grade 5 AEs t
28 weeks after last patient first Docetaxel dose (LPFD)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA-response
Time Frame: 28 after LPFD
PSA-response (PSA <=0.2, >0.2-4.0 und >4.0 ng/ml) determined at week 28 after LPFD
28 after LPFD
Time to castration-resistant prostate cancer
Time Frame: approximately 42 months
approx. every 90 days, defined as the time to PSA progression with serum testosterone being at castrate level <0.50 ng/mL, or the time to progression by soft tissue/visceral lesions or time to progression by bone lesions whatever comes first;
approximately 42 months
Overall survival
Time Frame: approximately 42 months
defined as the time (in days) from date of randomization until death from any cause
approximately 42 months
Time to initiation of subsequent antineoplastic therapy
Time Frame: approximately 42 months
approx. every 90 days up to the date of first subsequent antineoplastic therapy for prostate cancer
approximately 42 months
Symptomatic skeletal event free survival (SSE)
Time Frame: approximately 42 months
approx. every 90 days up to the first occurence of SSE, symptomatic skeletal event free survival, defined as the time from randomization to the first occurrence of SSE or death from any cause, whichever comes first. An SSE is defined as EBRT to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first.
approximately 42 months
Time to first symptomatic skeletal event (SSE)
Time Frame: approximately 42 months
approx. every 90 days up to the first occurence of SSE, defined as the time from randomization to the first occurrence of SSE. An SSE is defined as EBRT to relieve skeletal symptoms, or new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever comes first.
approximately 42 months
Time to pain progression
Time Frame: approximately 42 months
approx. every 90 days up to the first date a subject experiences a pain progression. Pain to be assessed with a patient reported questionaire
approximately 42 months
Time to worsening of physical symptoms of disease
Time Frame: approximately 42 months
approx. every 90 days up to the first date a subject experiences an increase in physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire
approximately 42 months
Treatment emergent adverse events
Time Frame: approximately 42 months
all grade AEs until the end-of-study treatment visit (to be analysed 26 weeks after last patient first Docetaxel, all grade AEs until the discontinuation visit, all and Study drug-related SAEs until the end of Survival Follow-up
approximately 42 months

Collaborators and Investigators

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

Sponsor

Jena University Hospital

Collaborators

Bayer

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 (Actual)

May 16, 2023

Primary Completion (Estimated)

February 1, 2025

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

December 14, 2022

First Submitted That Met QC Criteria

January 6, 2023

First Posted (Actual)

January 9, 2023

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UTN-01-2022

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

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.

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