Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer

Castration-Resistant Clinical Trial

— ARAMIS  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02200614
• Other study ID #: 17712
• Secondary ID: 2013-003820-36
• Status: Completed
• Phase: Phase 3
• Start date: September 12, 2014
• Est. completion date: June 14, 2021

Study information

• Verified date: June 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and efficacy of BAY1841788 (ODM-201) in patients with non-metastatic castration-resistant prostate cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1509
• Est. completion date: June 14, 2021
• Est. primary completion date: September 3, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
• Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.
• Prostate-specific Antigen (PSA) doubling time of = 10 months and PSA > 2ng/ml.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Blood counts at screening: haemoglobin = 9.0 g/dl,absolute neutrophil count = 1500/µl, platelet count = 100,000/µl.
• Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) = 2.5 x upper limit of normal (ULN), total bilirubin = 1.5 x ULN, creatinine = 2.0 x ULN.
• 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.

Exclusion Criteria:

• History of metastatic disease at any time or presence of detectable metastases.
• Acute toxicities of prior treatments and procedures not resolved to grade = 1 or baseline before randomisation.
• Prior treatment with: second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor.
• Use of estrogens or 5-a reductase inhibitors or AR inhibitors.
• Prior chemotherapy or immunotherapy for prostate cancer.
• Use of systemic corticosteroid.
• Radiation therapy within 12 weeks before randomisation.
• Severe or uncontrolled concurrent disease, infection or co-morbidity.
• Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.
• Known hypersensitivity to the study treatment or any of its ingredients.
• Major surgery within 28 days before randomisation.
• 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.
• Uncontrolled hypertension.
• Prior malignancy.
• Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
• Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
• Treatment with any investigational drug within 28 days before randomisation.
• Any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures.

Related Conditions & MeSH terms

• Castration-Resistant
• Prostate Cancer Non-Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• Darolutamide (Nubeqa, BAY1841788)
Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg.
• Placebo
Matching placebo 2 tablets twice daily with food.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Orion Corporation, Orion Pharma

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Brazil,  Bulgaria,  Canada,  Colombia,  Czechia,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastasis-Free Survival	Metastasis-Free Survival (MFS) is defined as the time from randomisation to evidence of metastasis or death from any cause, whichever occurs first (cut-off date 15 Nov 2019)	From randomization to the time approximately 385 MFS events were observed (approximately 48 months)
Secondary	Overall Survival - Primary Analysis	Overall Survival (OS) was defined as the time from randomization to death due to any cause.	From randomization of the first subject to the time approximatively 140 death events were observed (approximately 48 months)
Secondary	Time to Pain Progression - Primary Analysis	Time to pain progression (PP) is defined as time from randomization to pain progression, where progression is defined as an increase of 2 or more points from baseline in question 3 of the Brief Pain Inventory-Short Form questionnaire (BPI-SF) related to the worst pain in the last 24 hours taken as a 7-day average for post-baseline scores, or initiation of short or long-acting opioids for pain, whichever comes first. Initiation or change in the use of other non-opioid analgesics is not used in the analysis of pain progression.	From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
Secondary	Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Primary Analysis	The time to cytotoxic chemotherapy was defined as the time from randomization to the start of the first cytotoxic chemotherapy cycle.	From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
Secondary	Time to First Symptomatic Skeletal Event (SSE) - Primary Analysis	The time to the first SSE was defined as the time from randomization to the occurrence of the first SSE.	From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
Secondary	Overall Survival - Final Analysis	Overall Survival (OS) was defined as the time from randomization to death due to any cause. The final analysis was done at the time of the data cut-off (15 NOV 2019).	From randomization of the first subject to the time approximatively 254 death events were observed (approximately 56 months)
Secondary	Time to Pain Progression - Final Analysis	For time to pain progression, the analysis performed using the primary completion cut-off data (03 SEP 2018) was considered final and no new analysis was performed for time to pain progression.	From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
Secondary	Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Final Analysis	The time to cytotoxic chemotherapy was defined as the time from randomization to the start of the first cytotoxic chemotherapy cycle. The final analysis was done at the time of the data cut-off (15 NOV 2019).	From randomization until initiation of first cytotoxic chemotherapy treatment (approximately 59 months)
Secondary	Time to First Symptomatic Skeletal Event (SSE) - Final Analysis	The time to the first SSE was defined as the time from randomization to the occurrence of the first SSE. The final analysis was done at the time of the data cut-off (15 NOV 2019).	From randomization until occurrence of first SSE event (approximately 59 months)

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