ARASENS: ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer

• Sponsor: Bayer (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02799602
• Collaborator: Orion Corporation, Orion Pharma (Industry)
• Enrollment: 1,303
• Locations: 299
• Arms: 2
• Anticipated Duration (Months): 78.9
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the efficacy and safety of BAY1841788 (darolutamide (ODM-201)) in combination with standard androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone sensitive prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: BAY1841788 / darolutamide (ODM-201); Drug: Standard ADT (androgen deprivation therapy); Drug: Docetaxel; Drug: Placebo	Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter phase III study. The study population will consist of approximately 1300 subjects with metastatic hormone sensitive prostate cancer (mHSPC), who will be randomized (1:1 ratio) to receive 600 mg (2 x 300 mg tablets) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total daily dose of 1200 mg, in addition to standard androgen deprivation therapy (ADT) and docetaxel. Subjects will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels. All subjects will be treated with ADT as standard therapy. Six cycles of docetaxel will be administered after randomization.

The subjects considered for inclusion in the study will have metastatic prostate cancer and will be candidates for ADT and docetaxel.

Treatment with darolutamide (ODM-201)/placebo will be administered until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, until subject withdraws consent, withdrawal from the study at the discretion of the investigator or his/her designated associate(s), death, non-compliance, or if sponsor terminates the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1303 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Nov 30, 2016
• Actual Primary Completion Date: Oct 25, 2021
• Anticipated Study Completion Date: Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BAY1841788 /darolutamide (ODM-201)+standard ADT+Docetaxel Co-administration of BAY 1841788 / darolutamide (ODM-201), standard ADT and docetaxel	Drug: BAY1841788 / darolutamide (ODM-201); 600mg (2 tablets of 300 mg) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total a daily dose of 1200 mg in addition to standard ADT (luteinizing hormone releasing hormone (LHRH) agonist/antagonist or orchiectomy) and 6 cycles of docetaxel; Drug: Standard ADT (androgen deprivation therapy); As prescribed by the treating physician.; Drug: Docetaxel; As prescribed by the treating physician.
Placebo Comparator: Placebo + standard ADT + Docetaxel Co-administration of Placebo matching BAY 1841788 / darolutamide (ODM-201) tablets, standard ADT and docetaxel	Drug: Standard ADT (androgen deprivation therapy); As prescribed by the treating physician.; Drug: Docetaxel; As prescribed by the treating physician.; Drug: Placebo; Placebo matching darolutamide (ODM-201) tablets in appearance, bid orally with food, in addition to standard ADT (luteinizing hormone releasing hormone [LHRH] agonist/antagonist or orchiectomy) and 6 cycles of docetaxel.

Outcome Measures

Primary Outcome Measures

1. Overall survival [approximately 70 months]

   From date of randomization until death from any cause, during treatment and during active and long term follow-up

Secondary Outcome Measures

1. Time to castration resistant prostate cancer [approximately 70 months]

   Approximately every 12 weeks (according to standards of care) up to the time of PSA progression by soft tissue/visceral lesions or progression by bone lesions, whatever come first.

2. Time to initiation of subsequent antineoplastic therapy [approximately 70 months]

   Every 12 weeks up to the date of first subsequent antineoplastic therapy for prostate cancer.

3. Symptomatic skeletal event free survival (SSE-FS) [approximately 70 months]

   Every 12 weeks up to the first occurrence of SSE or death from any cause, whatever comes first SSE is defined as external beam radiation therapy (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.

4. Time to first symptomatic skeletal event (SSE) [approximately 70 months]

   Every 12 weeks up to the first occurrence of SSE. 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.

5. Time to initiation of opioid use [approximately 70 months]

   Every 12 weeks up to the opiod use.

6. Time to pain progression [approximately 70 months]

   Every 12 weeks up to the first date a subject experiences a pain progression. Pain to be assessed with a patient reported questionaire.

7. Time to worsening of physical symptoms of disease [approximately 70 months]

   Every 12 weeks up to the first date a subject experiences an increase in physical symptoms. Physical symptoms of disease to be assessed with a patient reported questionaire.

8. Number of participants with adverse events as a measure of safety and tolerability [approximately 70 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of prostate.

• Metastatic disease

• Candidates for ADT and docetaxel.

• Started ADT with or without first generation anti androgen, but no longer than 12 weeks before randomization

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Prior treatment with: LHRH agonist/antagonists; second generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide (ODM-201), other investigational AR inhibitors; CYP17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer; chemotherapy or immunotherapy for prostate cancer prior to randomization.

• Treatment with radiotherapy/radiopharmaceuticals within 2 weeks before randomization.

• 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)

• 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

• Gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study treatment.

• Inability to swallow oral medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chandler	Arizona	United States	85224
2		Tucson	Arizona	United States	85724
3		Beverly Hills	California	United States	90211-1850
4		Duarte	California	United States	91010
5		Los Angeles	California	United States	90073-1003
6		Stanford	California	United States	94305-5820
7		Washington	District of Columbia	United States	20007-2113
8		Boca Raton	Florida	United States	33486
9		Gainesville	Florida	United States	32610-0316
10		Tampa	Florida	United States	33612
11		Atlanta	Georgia	United States	30322
12		Chicago	Illinois	United States	60611
13		Peoria	Illinois	United States	61615-7828
14		Louisville	Kentucky	United States	40202
15		New Orleans	Louisiana	United States	70112
16		Baltimore	Maryland	United States	21231
17		Towson	Maryland	United States	21204
18		Boston	Massachusetts	United States	02111
19		Boston	Massachusetts	United States	02114-2696
20		Boston	Massachusetts	United States	02215
21		Detroit	Michigan	United States	48202
22		Billings	Montana	United States	59102
23		Omaha	Nebraska	United States	68130-5606
24		Lebanon	New Hampshire	United States	03756-1000
25		Camden	New Jersey	United States	08143
26		Englewood	New Jersey	United States	07361
27		Hackensack	New Jersey	United States	07601
28		Albuquerque	New Mexico	United States	87109
29		Bronx	New York	United States	10467-2490
30		Buffalo	New York	United States	14263-0001
31		New York	New York	United States	10032
32		Poughkeepsie	New York	United States	12601
33		Rochester	New York	United States	14642
34		Winston-Salem	North Carolina	United States	27157
35		Cleveland	Ohio	United States	44106
36		Columbus	Ohio	United States	43210
37		Columbus	Ohio	United States	43214-2416
38		Kettering	Ohio	United States	45409-1328
39		Oklahoma City	Oklahoma	United States	73104
40		Bala-Cynwyd	Pennsylvania	United States	19004
41		Camp Hill	Pennsylvania	United States	17011
42		Pittsburgh	Pennsylvania	United States	15212
43		Charleston	South Carolina	United States	29401-5799
44		Charleston	South Carolina	United States	29414
45		Greenville	South Carolina	United States	29607
46		Myrtle Beach	South Carolina	United States	29572
47		North Charleston	South Carolina	United States	29406
48		Dallas	Texas	United States	75231
49		Temple	Texas	United States	76508
50		Salt Lake City	Utah	United States	84112
51		Charlottesville	Virginia	United States	22908
52		Fairfax	Virginia	United States	22031
53		Richmond	Virginia	United States	23298-5054
54		Everett	Washington	United States	98201
55		Milwaukee	Wisconsin	United States	53226
56		Randwick	New South Wales	Australia	2031
57		Sydney	New South Wales	Australia	2010
58		Adelaide	South Australia	Australia	5000
59		Kurralta Park	South Australia	Australia	5037
60		Melbourne	Victoria	Australia	3065
61		Wilrijk	Antwerpen	Belgium	2610
62		Bruxelles - Brussel		Belgium	1000
63		Bruxelles - Brussel		Belgium	1070
64		Bruxelles - Brussel		Belgium	1200
65		Charleroi		Belgium	6000
66		Gent		Belgium	9000
67		Namur		Belgium	5000
68		Salvador	Bahia	Brazil	41253-190
69		Cachoeiro de Itapemirim	Espírito Santo	Brazil	29308-020
70		Curitiba	Parana	Brazil	81520-060
71		Natal	Rio Grande Do Norte	Brazil	59075-740
72		Porto Alegre	Rio Grande Do Sul	Brazil	90050 170
73		Santo André	Sao Paulo	Brazil	09060-650
74		São Paulo	Sao Paulo	Brazil	04014-002
75		Rio de Janeiro		Brazil	20231-050
76		Rio de Janeiro		Brazil	22793-080
77		Gabrovo		Bulgaria	5300
78		Pleven		Bulgaria	5800
79		Sofia		Bulgaria	1303
80		Sofia		Bulgaria	1431
81		Sofia		Bulgaria	1784
82		Varna		Bulgaria	9010
83		Vratsa		Bulgaria	3000
84		Calgary	Alberta	Canada	T2N 4N2
85		Edmonton	Alberta	Canada	T6G 1Z2
86		Toronto	Ontario	Canada	M4N 3M5
87		Toronto	Ontario	Canada	M5G 2M9
88		Montreal	Quebec	Canada	H2L 4M1
89		Hefei	Anhui	China	230001
90		Xiamen	Fujian	China	361003
91		Guangzhou	Guangdong	China	510120
92		Shijiazhuang	Hebei	China	050000
93		Zhengzhou	Henan	China	450008
94		Wuhan	Hubei	China	430030
95		Wuhan	Hubei	China	430079
96		Changsha	Hunan	China	410013
97		Nanjing	Jiangsu	China	210008
98		Nanjing	Jiangsu	China	210009
99		Nanchang	Jiangxi	China	330006
100		Changchun	Jilin	China	130000
101		Shengyang	Liaoning	China	110042
102		Shenyang	Liaoning	China	110001
103		Xi'an	Shaanxi	China	710061
104		Jinan	Shandong	China	250012
105		Jinan	Shandong	China	250021
106		Yantai	Shandong	China	264000
107		Hangzhou	Zhejiang	China	310009
108		Hangzhou	Zhejiang	China	310014
109		Wenzhou	Zhejiang	China	325000
110		Beijing		China	100034
111		Beijing		China	100050
112		Beijing		China	100083
113		Beijing		China	100142
114		Beijing		China	100730
115		Chongqing		China	400030
116		Shanghai		China	200032
117		Shanghai		China	200040
118		Shanghai		China	200072
119		Shanghai		China	200080
120		Shanghai		China	200092
121		Tianjin		China	300052
122		Tianjin		China	300060
123		Brno		Czechia	602 00
124		Brno		Czechia	656 91
125		Praha 10		Czechia	10034
126		Praha 2		Czechia	120 00
127		Praha 2		Czechia	128 08
128		Praha 5		Czechia	150 06
129		Praha 8		Czechia	180 81
130		Helsinki		Finland	00290
131		Jyväskylä		Finland	40620
132		Kuopio		Finland	70210
133		Mikkeli		Finland	FIN-50100
134		Oulu		Finland	90220
135		Tampere		Finland	33521
136		Turku		Finland	20520
137		Angers Cedex		France	49055
138		Besancon		France	25030
139		Bordeaux Cedex		France	33076
140		Brest		France	29200
141		Cergy Pontoise		France	95303
142		Clermont-ferrand		France	63011
143		Creteil		France	94010
144		Marseille		France	13273
145		Montpellier Cedex		France	34298
146		Nancy		France	54100
147		Pierre Benite		France	69495
148		Poitiers		France	86021
149		REIMS cedex		France	51726
150		Saint Herblain Cedex		France	44805
151		Saint-gregoire		France	35760
152		Strasbourg		France	67033
153		Villejuif Cedex		France	94805
154		Freiburg	Baden-Württemberg	Germany	79106
155		Nürtingen	Baden-Württemberg	Germany	72622
156		Tübingen	Baden-Württemberg	Germany	72076
157		Ulm	Baden-Württemberg	Germany	89075
158		Erlangen	Bayern	Germany	91054
159		Rostock	Mecklenburg-Vorpommern	Germany	18107
160		Braunschweig	Niedersachsen	Germany	38126
161		Münster	Nordrhein-Westfalen	Germany	48149
162		Jena	Thüringen	Germany	07747
163		Berlin		Germany	12203
164		Magdeburg		Germany	39120
165		Beer Sheva		Israel	8410101
166		Haifa		Israel	3109601
167		Holon		Israel	5822012
168		Jerusalem		Israel	9112001
169		Petach Tikva		Israel	4941492
170		Tel Aviv		Israel	6423906
171		Zefat		Israel	1311001
172		Zrifin		Israel	7030000
173		Bologna	Emilia-Romagna	Italy	40138
174		Parma	Emilia-Romagna	Italy	43126
175		Roma	Lazio	Italy	00152
176		Milano	Lombardia	Italy	20141
177		Novara	Piemonte	Italy	28100
178		Torino	Piemonte	Italy	10043
179		Trento	Trentino-Alto Adige	Italy	38100
180		Padova	Veneto	Italy	35128
181		Verona	Veneto	Italy	37134
182		Nagoya	Aichi	Japan	466-8560
183		Hirosaki	Aomori	Japan	036-8563
184		Asahi	Chiba	Japan	289-2511
185		Kashiwa	Chiba	Japan	277-8577
186		Sakura	Chiba	Japan	285-8741
187		Matsuyama	Ehime	Japan	791-0280
188		Sapporo	Hokkaido	Japan	003-0804
189		Kobe	Hyogo	Japan	650-0017
190		Kanazawa	Ishikawa	Japan	920-8530
191		Kanazawa	Ishikawa	Japan	920-8641
192		Kita	Kagawa	Japan	761-0793
193		Yokohama	Kanagawa	Japan	232-0024
194		Yokohama	Kanagawa	Japan	241-8515
195		Tsu	Mie	Japan	514-8507
196		Sendai	Miyagi	Japan	980-8574
197		Kashihara	Nara	Japan	634-8522
198		Osakasayama	Osaka	Japan	589-8511
199		Suita	Osaka	Japan	565-0871
200		Hamamatsu	Shizuoka	Japan	431-3192
201		Shimotsuke	Tochigi	Japan	329-0498
202		Utsunomiya	Tochigi	Japan	321-0974
203		Bunkyo-ku	Tokyo	Japan	113-8431
204		Bunkyo-ku	Tokyo	Japan	113-8603
205		Bunkyo-ku	Tokyo	Japan	113-8655
206		Koto-ku	Tokyo	Japan	135-8550
207		Meguro-ku	Tokyo	Japan	152-8902
208		Minato-ku	Tokyo	Japan	105-8471
209		Mitaka	Tokyo	Japan	181-8611
210		Nakano-ku	Tokyo	Japan	164-8541
211		Shinjuku-ku	Tokyo	Japan	160-8582
212		Shinjuku-ku	Tokyo	Japan	162-8543
213		Yonago	Tottori	Japan	683-8504
214		Ube	Yamaguchi	Japan	755-8505
215		Chiba		Japan	260-8677
216		Chiba		Japan	260-8717
217		Fukuoka		Japan	811-1395
218		Gifu		Japan	500-8717
219		Kumamoto		Japan	860-0008
220		Miyazaki		Japan	889-1692
221		Nagasaki		Japan	852-8501
222		Okayama		Japan	700-8558
223		Osaka		Japan	541-8567
224		Osaka		Japan	545-8586
225		Tokushima		Japan	770-8503
226		Wakayama		Japan	641-8510
227		Gwangju	Gwangju Gwang''yeogsi	Korea, Republic of	61469
228		Seongnam-si	Gyeonggido	Korea, Republic of	13620
229		Seoul	Seoul Teugbyeolsi	Korea, Republic of	03080
230		Seoul	Seoul Teugbyeolsi	Korea, Republic of	06273
231		Busan		Korea, Republic of	47392
232		Daegu		Korea, Republic of	41404
233		Gyeonggi-do		Korea, Republic of	11923
234		Seoul		Korea, Republic of	02841
235		Seoul		Korea, Republic of	03722
236		Seoul		Korea, Republic of	05505
237		Seoul		Korea, Republic of	06351
238		Seoul		Korea, Republic of	06591
239		Ciudad de Mexico	Distrito Federal	Mexico	06760
240		México, D. F.	Distrito Federal	Mexico	06760
241		Cuernavaca	Morelos	Mexico	62290
242		Monterrey	Nuevo Leon	Mexico	64460
243		Santiago de Querétaro	Querétaro	Mexico	76000
244		Mazatlán	Sinaloa	Mexico	82110
245		Amsterdam		Netherlands	1066 CX
246		Amsterdam		Netherlands	1105 AZ
247		Den Haag		Netherlands	2545 AA
248		Dordrecht		Netherlands	3318 AT
249		Geleen		Netherlands	6162 BG
250		Hilversum		Netherlands	1213 XZ
251		Hoofddorp		Netherlands	2134 TM
252		Tilburg		Netherlands	5042 AD
253		Lodz		Poland	90-302
254		Lublin		Poland	20-362
255		Rybnik		Poland	44-200
256		Siedlce		Poland	08-110
257		Waliszew		Poland	05-135
258		Warszawa		Poland	02-781
259		Barnaul		Russian Federation	656045
260		Chelyabinsk		Russian Federation	454048
261		Chelyabinsk		Russian Federation	454087
262		Moscow		Russian Federation	115478
263		Moscow		Russian Federation	125284
264		Novosibirsk		Russian Federation	630099
265		Omsk		Russian Federation	644013
266		St. Petersburg		Russian Federation	188663
267		St. Petersburg		Russian Federation	194017
268		St. Petersburg		Russian Federation	197136
269		Sabadell	Barcelona	Spain	08208
270		Palma de Mallorca	Illes Baleares	Spain	07120
271		Barcelona		Spain	08003
272		Barcelona		Spain	08035
273		Barcelona		Spain	08036
274		Barcelona		Spain	08041
275		Cáceres		Spain	10003
276		Córdoba		Spain	14004
277		Lugo		Spain	27003
278		Madrid		Spain	28034
279		Madrid		Spain	28041
280		Málaga		Spain	29010
281		Valencia		Spain	46009
282		Göteborg		Sweden	413 45
283		Lund		Sweden	221 85
284		Solna		Sweden	171 64
285		Umeå		Sweden	901 85
286		Uppsala		Sweden	751 85
287		Kaohsiung		Taiwan	807
288		Taichung		Taiwan	40447
289		Taipei		Taiwan	100
290		Taipei		Taiwan	11217
291		Taoyuan		Taiwan	33305
292		Colchester	Essex	United Kingdom	CO4 5JL
293		Romford	Essex	United Kingdom	RM7 0AG
294		Middlesborough	North Yorkshire	United Kingdom	TS4 3BW
295		Belfast		United Kingdom	BT9 7AB
296		Glasgow		United Kingdom	G12 0YN
297		London		United Kingdom	NW1 2PG
298		London		United Kingdom	SW3 6JJ
299		London		United Kingdom	W6 8RF

Sponsors and Collaborators

• Bayer
• Orion Corporation, Orion Pharma

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02799602
• Other Study ID Numbers: 17777; 2015-002590-38
• First Posted: Jun 15, 2016
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Bayer: Metastatic hormone sensitive prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Hypersensitivity; Docetaxel; Androgens

Study Results

No Results Posted as of Aug 4, 2022