NCT02200614 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2022-06-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Metastasis-Free Survival

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outcome · POSTED

Overall Survival - Primary Analysis

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outcome · POSTED

Time to Pain Progression - Primary Analysis

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outcome · POSTED

Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Primary Analysis

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outcome · POSTED

Time to First Symptomatic Skeletal Event (SSE) - Primary Analysis

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outcome · POSTED

Overall Survival - Final Analysis

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outcome · POSTED

Time to Pain Progression - Final Analysis

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outcome · POSTED

Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Final Analysis

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outcome · POSTED

Time to First Symptomatic Skeletal Event (SSE) - Final Analysis

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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-α 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: MALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg.
intervention Names
Drug: Darolutamide (Nubeqa, BAY1841788)
label
Darolutamide (BAY1841788)
type
EXPERIMENTAL
description
Participants received matching placebo 2 tablets twice daily with food.
intervention Names
Drug: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Darolutamide (BAY1841788)
description
Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg.
name
Darolutamide (Nubeqa, BAY1841788)
other Names
ODM-201
type
DRUG
arm Group Labels
Placebo
description
Matching placebo 2 tablets twice daily with food.
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 1509
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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)
measure
Metastasis-Free Survival
time Frame
From randomization to the time approximately 385 MFS events were observed (approximately 48 months)

secondary Outcomes

description
Overall Survival (OS) was defined as the time from randomization to death due to any cause.
measure
Overall Survival - Primary Analysis
time Frame
From randomization of the first subject to the time approximatively 140 death events were observed (approximately 48 months)
description
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.
measure
Time to Pain Progression - Primary Analysis
time Frame
From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
description
The time to cytotoxic chemotherapy was defined as the time from randomization to the start of the first cytotoxic chemotherapy cycle.
measure
Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Primary Analysis
time Frame
From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
description
The time to the first SSE was defined as the time from randomization to the occurrence of the first SSE.
measure
Time to First Symptomatic Skeletal Event (SSE) - Primary Analysis
time Frame
From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
description
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).
measure
Overall Survival - Final Analysis
time Frame
From randomization of the first subject to the time approximatively 254 death events were observed (approximately 56 months)
description
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.
measure
Time to Pain Progression - Final Analysis
time Frame
From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
description
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).
measure
Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Final Analysis
time Frame
From randomization until initiation of first cytotoxic chemotherapy treatment (approximately 59 months)
description
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).
measure
Time to First Symptomatic Skeletal Event (SSE) - Final Analysis
time Frame
From randomization until occurrence of first SSE event (approximately 59 months)

Full study description

brief 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.

Source references

references

citation
Saar M, Fizazi K, Shore ND, Smith M, Damber JE, Semenov A, Ribal MJ, Birtle A, Rigaud J, Wallis CJD, Grimm MO, Halabi S, Armstrong AJ, Mohamed AF, Adorjan P, Srinivasan S, Verholen F, Morgans AK, Siemens DR. Effects of Prior Local Therapy by Radical Prostatectomy or Radiotherapy on the Efficacy and Quality of Life of Patients Treated With Darolutamide in ARAMIS. Cancer Med. 2026 Jan;15(1):e71343. doi: 10.1002/cam4.71343.
pmid
41450200
type
DERIVED
citation
Ni X, Sui J, Wang B, Wang H, Freedland SJ, Ye D, Zhu Y. Lower Testosterone Level and Metastases-Free Survival in Patients With Nonmetastatic Castration-Resistant Prostate Cancer Treated With Novel Antiandrogens: A Post Hoc Analysis of SPARTAN and ARAMIS. J Urol. 2025 Jul;214(1):10-17. doi: 10.1097/JU.0000000000004545. Epub 2025 Mar 25.
pmid
40132221
type
DERIVED
citation
Shore ND, Gratzke C, Feyerabend S, Werbrouck P, Carles J, Vjaters E, Tammela TLJ, Morris D, Aragon-Ching JB, Concepcion RS, Emmenegger U, Fleshner N, Grabbert M, Lietuvietis V, Mahammedi H, Cruz FM, Paula A, Pieczonka C, Rannikko A, Richardet M, Silveira G, Kuss I, Le Berre MA, Verholen F, Sarapohja T, Smith MR, Fizazi K. Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS. Oncologist. 2024 Jul 5;29(7):581-588. doi: 10.1093/oncolo/oyae019.
pmid
38394384
type
DERIVED
citation
Fizazi K, Shore ND, Smith M, Ramos R, Jones R, Niegisch G, Vjaters E, Wang Y, Srinivasan S, Sarapohja T, Verholen F. Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial. Eur J Cancer. 2023 Oct;192:113258. doi: 10.1016/j.ejca.2023.113258. Epub 2023 Jul 27.
pmid
37660438
type
DERIVED
citation
Carles J, Medina-Lopez RA, Puente J, Gomez-Ferrer A, Nebra JC, Saez Medina MI, Ribal MJ, Antolin AR, Alvarez-Ossorio JL, Suarez Novo JF, Agut CM, Srinivasan S, Ortiz J, Fizazi K. Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis. Future Oncol. 2023 Apr;19(12):819-828. doi: 10.2217/fon-2022-1131. Epub 2023 May 24.
pmid
37222151
type
DERIVED
citation
Shore ND, Stenzl A, Pieczonka C, Klaassen Z, Aronson WJ, Karsh L, Ryan CJ, Ortiz J, Srinivasan S, Mohamed AF, Verholen F. Impact of darolutamide on local symptoms: pre-planned and post hoc analyses of the ARAMIS trial. BJU Int. 2023 Apr;131(4):452-460. doi: 10.1111/bju.15887. Epub 2022 Sep 29.
pmid
36087070
type
DERIVED
citation
Chowdhury S, Oudard S, Uemura H, Joniau S, Dearden L, Capone C, Van Sanden S, Diels J, Hadaschik BA. Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison. Adv Ther. 2022 Jan;39(1):518-531. doi: 10.1007/s12325-021-01885-6. Epub 2021 Nov 19.
pmid
34797506
type
DERIVED
citation
Fizazi K, Blue I, Nowak JT. Darolutamide and survival in nonmetastatic, castration-resistant prostate cancer: a patient perspective of the ARAMIS trial. Future Oncol. 2021 May;17(14):1699-1707. doi: 10.2217/fon-2020-1291. Epub 2021 Feb 8.
pmid
33554636
type
DERIVED
citation
Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. doi: 10.1056/NEJMoa2001342.
pmid
32905676
type
DERIVED
citation
Shore N, Zurth C, Fricke R, Gieschen H, Graudenz K, Koskinen M, Ploeger B, Moss J, Prien O, Borghesi G, Petrenciuc O, Tammela TL, Kuss I, Verholen F, Smith MR, Fizazi K. Evaluation of Clinically Relevant Drug-Drug Interactions and Population Pharmacokinetics of Darolutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Results of Pre-Specified and Post Hoc Analyses of the Phase III ARAMIS Trial. Target Oncol. 2019 Oct;14(5):527-539. doi: 10.1007/s11523-019-00674-0.
pmid
31571095
type
DERIVED
citation
Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. doi: 10.1056/NEJMoa1815671. Epub 2019 Feb 14.
pmid
30763142
type
DERIVED