A MULTINATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III EFFICACY AND SAFETY STUDY OF DAROLUTAMIDE ODM-201 IN MEN WITH HIGH-RISK NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

• Register: EUCTR
• Last refreshed on: 5 July 2021
• Main ID: EUCTR2013-003820-36-HU
• Date of registration: 06/06/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: A MULTINATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III EFFICACY AND SAFETY STUDY OF DAROLUTAMIDE ODM-201 IN MEN WITH HIGH-RISK NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
• Scientific title: A MULTINATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III EFFICACY AND SAFETY STUDY OF DAROLUTAMIDE ODM-201 IN MEN WITH HIGH-RISK NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER - Aramis
• Date of first enrolment: 11/08/2014
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003820-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: yes; 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

Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, 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:
1. Written informed consent (IC) obtained.
2. Males aged > = 18 years.
3. Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
4. CRPC is defined as 3 rising PSA levels after the nadir taken at least 1 week apart during
ADT. If the patient has a history of antiandrogen use, the most recent
PSA value must be obtained at least 4 weeks after antiandrogen
withdrawal. See section 6.1.1 of the Protocol for further detials.
5. Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy. Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
6. PSADT of = 10 months and PSA > 2 ng/ml at screening. See section 6.1.1 of the Protocol for further detials.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
8. Blood counts at screening: haemoglobin = 9.0 g/dl, absolute neutrophil count = 1500/µl (1.5x10^9/l), platelet count = 100,000/µl (100x10^9/l ) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening).
9. Screening values of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) = 2.5 x upper limit of normal (ULN), total bilirubin = 1.5 x ULN (except patients with a diagnosis of Gilbert’s disease), creatinine = 2.0 x ULN.
10. Sexually active patients, unless surgically sterile, must agree to use
condoms as an effective barrier method and refrain from sperm donation
during the study treatment and for 3 months after the end of the study
treatment.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1200

Exclusion criteria:
1. History of metastatic disease at any time or presence of detectable metastases by blinded central reading within 42 days prior to start of study treatment. Presence of pelvic lymph nodes < 2 cm in short axis below the aortic bifurcation is allowed. See section 6.1.1 of the Protocol for further detials.
2. Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer.
3. Acute toxicities of prior treatments and procedures not resolved to grade <=1 or baseline before randomisation.
4. Prior treatment with: second generation AR inhibitors such as enzalutamide, ARN-509, darolutamide , other investigational AR inhibitors,
CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or
oral ketoconazole longer than for 28 days.
5. Use of estrogens or 5-a reductase inhibitors (finasteride, dutasteride) within 28 days before randomization and AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) at least 28 days before screening
6. Prior chemotherapy or immunotherapy for prostate cancer, except adjuvant/neoadjuvant treatment completed > 2 years before randomisation.
7. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation.
8. Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks before randomisation.
9. Severe or uncontrolled concurrent disease, infection or co-morbidity that, in the opinion of the investigator, would make the patient inappropriate for enrolment.
10. Treatment with an osteoclast-targeted therapy (bisphosphonate or
denosumab) to prevent skeletal-related events within 12 weeks before
randomisation. Patients receiving osteoclast-targeted therapy to prevent
bone loss at a dose and schedule indicated for osteoporosis may
continue treatment at the same dose and schedule.
11. Known hypersensitivity to the study treatment or any of its ingredients.
12. Major surgery within 28 days before randomisation.
13. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
14. Uncontrolled hypertension as indicated by a systolic BP >=160 mmHg or diastolic BP >=100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications.
15. 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 ago and from which the patient has been disease-free.
16. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
17. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
18. Treatment with any investigational drug within 28 days before randomisation.
19. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures.
20. Unable to swallow study medications and comply with study requirements.


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

Health Condition(s) or Problem(s) studied

High-risk, non-metastatic castration-resistant prostate cancer (MedDRA: hormonerefractory prostate cancer)
MedDRA version: 21.1 Level: LLT Classification code 10066489 Term: Progression of prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Product Name: Darolutamide
Product Code: BAY 1841788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Darolutamide
Current Sponsor code: BAY 1841788
Other descriptive name: ODM-201
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

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate the superiority of darolutamide vs. placebo in metastasis free survival (MFS) in patients with high-risk nmCRPC

Primary end point(s): The primary efficacy variable is metastasis free survival (MFS), defined as time between randomisation and evidence of metastasis or death from any cause, whichever occurs first

Secondary Objective: The secondary objectives of this study are to demonstrate the benefit of darolutamide for:
Overal survival (OS), time to first symptomatic skeletal related event (SSE), time to initiation of first cytotoxic chemotherapy for prostate cancer, time to pain progression and
to characterise the safety and tolerability of darolutamide

Timepoint(s) of evaluation of this end point: Will be evaluated at about 385 events

Secondary Outcome(s)

Secondary end point(s): Overal survival (OS) is defined as time from randomisation to date of death from any cause. Survival status will be assessed from randomisation until the end of follow-up period.
Time to first Symptomatic Skeletal Event (SSE) is defined as time from randomisation to the first occurrence of SSE. SSE is defined as External Beam Radiation Therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone
fracture, or occurrence of spinal cord compression or tumour-related orthopaedic surgical intervention, whichever comes first.
Time to cytotoxic chemotherapy is defined as time from randomisation to initiation of the first cytotoxic chemotherapy.
Pain progression is defined as an increase of 2 points from baseline in question 3 of Brief Pain Inventory - Short Form (BPI-SF) (related to the worst pain in the last 24 hours) taken as a 7-day average, or initiation of short or long-acting opioids for pain, whichever comes first.

Timepoint(s) of evaluation of this end point: Survival status will be assessed from randomisation until the end of follow-up period.
SSE will be assessed from randomisation until the first occurrence of SSE.
Use of cytotoxic chemotherapy will be assessed from randomisation until the first use of cytotoxic chemotherapy.
Pain will be assessed with the BPI-SF questionnaire (Appendix 4), pain diary and opioid use from baseline until the end of follow-up period.

Secondary ID(s)

2013-003820-36-SE

3104007

BAY1841788/17712

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date: 31/07/2014
Contact: