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

NCT05676203 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: UTN-01-2022
• Study Type: interventional
• Target: 250
• Locations: 2 countries
• Sites: 43

Brief Summary

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).

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Keywords

prostate cancer; metastatic prostate cancer; metastatic hormone-sensitive prostate cancer; docetaxel; darolutamide; safety

Outcome Measures

Primary Outcomes (1)

• Rate of grade 3-5 AEs

  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 Outcomes (9)

• PSA-response

  28 after LPFD

• Time to castration-resistant prostate cancer

  approximately 42 months

• Overall survival

  approximately 42 months

• Time to initiation of subsequent antineoplastic therapy

  approximately 42 months

• Symptomatic skeletal event free survival (SSE)

  approximately 42 months

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

6 x Docetaxel 75 mg/m2 every 3 weeks of a 3 week cycle Co-administration of docetaxel, darolutamide and standard ADT

Drug: Standard ADT (androgen deprivation therapy); Drug: Standard Darolutamide; Drug: Docetaxel

Arm 2

EXPERIMENTAL

6 x Docetaxel 50 mg/ m2 every 2 weeks of a 4 week cycle Co-administration of docetaxel, darolutamide and standard ADT

Drug: Standard ADT (androgen deprivation therapy); Drug: Standard Darolutamide; Drug: Docetaxel

Interventions

Standard ADT (androgen deprivation therapy) DRUG

as prescribed by the treating physician.

Arm 1; Arm 2

Standard Darolutamide DRUG

2x600 mg/d as prescribed by the treating physician

Arm 1; Arm 2

Docetaxel DRUG

Docetaxel

Arm 1; Arm 2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Jena University Hospital: lead
• Bayer: collaborator

Study Sites (43)

Ordensklinikum Linz GmbH, Elisabethinen

Linz, 4020, Austria

Location

Krankenhaus der Barmherzigen Brüder

Vienna, 1020, Austria

Location

Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Klinikum Wetzlar

Wetzlar, Hesse, 35578, Germany

Location

Med. Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Urologische Klinik München Planegg

Planegg, München, 82152, Germany

Location

Urologicum Duisburg

Duisburg, North Rhine-Westphalia, 47169, Germany

Location

Brüderkrankenhaus St- Josef Paderborn

Paderborn, North Rhine-Westphalia, 33098, Germany

Location

Urologisches Zentrum Euregio

Würselen, North Rhine-Westphalia, 52146, Germany

Location

Krankenhaus Martha-Maria Halle Dölau gGmbH

Halle, Saxony-Anhalt, 06120, Germany

Location

Praxisgemeinschaft f. Onkologie & Urologie

Wilhelmshaven, Schleswig-Holstein, 26389, Germany

Location

University Hospital Jena, Department of Urology

Jena, Thuringia, 07747, Germany

Location

Marien Krankenhaus

Bergisch Gladbach, 51465, Germany

Location

Vivantes Prostatazentrum im Klinikum am Urban

Berlin, 10967, Germany

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

Urologie Schlosscarree

Braunschweig, 38100, Germany

Location

UROLOGIE BAYENTHAL Gemeinschaftspraxis

Cologne, Germany

Location

Städtisches Klinikum Dessau

Dessau, 06847, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Helios Klinikum Erfurt

Erfurt, 99089, Germany

Location

Uniklinikum Erlangen

Erlangen, 91054, Germany

Location

KEM | Evang. Kliniken Essen-Mitte

Essen, 45136, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

Location

Universitäts Klinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen

Giessen, 35392, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

St. Anna Hospital Herne

Herne, 44625, Germany

Location

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Universitätsklinikum Gießen und Marburg - Standort Marburg

Marburg, 35043, Germany

Location

LMU Klinikum

München, 81377, Germany

Location

TUM Klinikum

München, 81675, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

St. Theresien Krankenhaus Nürnberg

Nuremberg, 90491, Germany

Location

Studienpraxis Urologie

Nürtingen, 72622, Germany

Location

Brüderkrankenhaus

Trier, 54292, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Helios Universitätsklinikum Wuppertal

Wuppertal, 42283, Germany

Location

Uniklinikum Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Androgen Antagonists; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Marc-Oliver Grimm

Study Record Dates

• First Submitted: December 14, 2022
• First Posted: January 9, 2023
• Study Start: May 16, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (41); AU (2)