Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Conditions
Keywords
prostate cancer, metastatic prostate cancer, metastatic hormone-sensitive prostate cancer, docetaxel, darolutamide, safety
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).
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).
Interventions
as prescribed by the treating physician.
DRUGStandard Darolutamide
2x600 mg/d as prescribed by the treating physician
DRUGDocetaxel
Docetaxel
Sponsors
Jena University Hospital
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of grade 3-5 AEs | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA-response | 28 after LPFD | PSA-response (PSA \<=0.2, \>0.2-4.0 und \>4.0 ng/ml) determined at week 28 after LPFD |
| Time to castration-resistant prostate cancer | 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; |
| Overall survival | approximately 42 months | defined as the time (in days) from date of randomization until death from any cause |
| Time to initiation of subsequent antineoplastic therapy | approximately 42 months | approx. every 90 days up to the date of first subsequent antineoplastic therapy for prostate cancer |
| Symptomatic skeletal event free survival (SSE) | 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. |
| Time to first symptomatic skeletal event (SSE) | 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. |
| Time to pain progression | 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 |
| Time to worsening of physical symptoms of disease | 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 |
| Treatment emergent adverse events | 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 |
Countries
Austria, Germany
Outcome results
None listed