Darolutamide in addition to standard hormone therapy and docetaxel in metastatic hormone-sensitive prostate cancer

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2015-002590-38-PL
• Date of registration: 03/01/2017
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Darolutamide in addition to standard hormone therapy and docetaxel in metastatic hormone-sensitive prostate cancer
• Scientific title: A randomized, double-blind, placebo-controlled Phase III study of darolutamide (ODM-201) versus placebo in addition to standard androgen deprivation therapy and docetaxel in patients with metastatic hormone-sensitive prostate cancer - ARASENS
• Date of first enrolment: 06/02/2017
• Target sample size: 1300
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002590-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Finland, France, Germany, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet the following criteria at the time of Screening:
1. Written informed consent.
2. Males =18 years of age.
3. Histologically or cytologically confirmed adenocarcinoma of prostate.
4. 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 by Investigator and confirmed by central radiology review. Metastatic disease is defined as either malignant lesions in bone scan or measurable lymph nodes above the aortic bifurcation 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 regional lymph node metastases only (N1, below the aortic bifurcation) will not be eligible for the study. Only subjects with non-regional lymph node metastases (M1a) and/or bone metastases (M1b) and/or other sites of metastases with or without bone disease (M1c) will be eligible.
5. Subjects must be candidates for ADT and docetaxel therapy per Investigator’s judgment.
6. 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.
7. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
8. 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).
9. Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) =1.5 x upper limit of normal (ULN), total bilirubin =ULN, creatinine =2.0 x ULN.
10. 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/placebo and for 3 months after treatment with darolutamide/placebo and 6 months after treatment with docetaxel.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 650
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 650

Exclusion criteria:
Subjects who meet any of the following criteria at the time of Screening will be excluded:
1. Prior treatment with:
• LHRH agonist/antagonists started more than 12 weeks before randomization
• Second-generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide, other
investigational AR inhibitors
• Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer
• Chemotherapy or immunotherapy for prostate cancer prior to randomization
2. Treatment with radiotherapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 2 weeks before randomization.
3. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.
4. Contraindication to both CT and MRI contrast agent.
5. 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).
6. Uncontrolled hypertension as indicated by a resting systolic BP =160 mmHg or diastolic BP =100 mmHg despite medical management.
7. 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.
8. A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study drug.
9. An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need of treatment.
10. 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).
11. 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.
12. Inability to swallow oral medications.
13. Close affiliation with the investigational site (e.g., a close relative of the Investigator, dependent person [e.g., employee or student of the investigational site]).
14. Previous assignment to treatment in this study.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Metastatic hormone-sensitive prostate cancer (mHSPC)
MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Darolutamide 300mg film-coated tablet
Product Code: BAY 1841788 300mg film-coated tablet
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BAY 1841788
CAS Number: 1297538-32-9
Current Sponsor code: Darolutamide
Other descriptive name: BAY 1841788
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Docetaxel cell pha?m 20 mg/ml concent?ate f?? solution f?? infusion
Product Name: Docetaxel cell pha?m 20 mg/ml concent?ate f?? solution f?? infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOCETAXEL
Other descriptive name: DOCETAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The primary analysis will be performed when approximately 509 deaths occur in the 2 treatment arms combined. The expected study duration for 509 deaths is approximately 70 months.

Primary end point(s): Overall survival, defined as the time (in days) from date of randomization until death from any cause.

Main Objective: • To demonstrate the superiority in overall survival of darolutamide in addition to standard androgen deprivation therapy (ADT) and docetaxel over placebo in addition to standard ADT and docetaxel

Secondary Objective: • Time to castration-resistant prostate cancer
• Time to initiation of subsequent antineoplastic therapy
• Symptomatic skeletal event free survival (SSE-FS)
• Time to first symptomatic skeletal event (SSE)
• Time to initiation of opioid use for =7 consecutive days
• Time to pain progression
• Time to worsening of physical symptoms of disease based on Functional assessment of cancer therapy / National Comprehensive Cancer Network prostate cancer symptom index 17 (NCCN-FACT FPSI-17)
• Safety

Secondary Outcome(s)

Secondary end point(s): • Time to castration-resistant prostate cancer
• Time to initiation of subsequent antineoplastic therapy
• Symptomatic skeletal event free survival (SSE-FS)
• Time to first symptomatic skeletal event (SSE)
• Time to initiation of opioid use for =7 consecutive days
• Time to pain progression
• Time to worsening of physical symptoms of disease based on NCCN-FACT FPSI-17
• Safety

Timepoint(s) of evaluation of this end point: •Time to PSA progression with serum testosterone being at castrate level <0.50 ng/mL,or the time to progression by soft tissue lesions or time to progression by bone lesions
•Time from randomization to initiation of first subsequent antineoplastic therapy for prostate cancer
•Time from randomization to the first occurrence of SSE or death from any cause
•Time from randomization to the first occurrence of SSE
•Time from date of randomization to the date of first opiate use for =7 consecutive days
•Interval from randomization to the first date a subject experiences a pain progression
•Interval from randomization to the first date a subject experiences an increase in physical symptoms based on the NCCN FACT FPSI 17 questionnaire.
•Refer to protocol section 10.3.3 for safety variables

Secondary ID(s)

2015-002590-38-GB

17777

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date: 31/01/2017
Contact: