An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS

Sponsor

Aragon Pharmaceuticals, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02531516

Collaborator

(none)

1,503

Enrollment

271

Locations

Arms

130.6

Anticipated Duration (Months)

5.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if apalutamide plus gonadotropin releasing hormone (GnRH) agonist in participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy results in an improvement of metastasis-free survival.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Apalutamide Drug: Bicalutamide Drug: Bicalutamide Placebo Drug: Apalutamide Placebo Drug: GnRH (agonist) Radiation: 74-80 Grays (units of radiation)	Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter study of apalutamide plus GnRH agonist compared with GnRH agonist among participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (RT). The study will include a Screening Phase, Treatment Phase, a Posttreatment Phase, and a Long-term Follow-up Phase. Participants will either receive either apalutamide (experimental) or bicalutamide 50 milligram (mg) capsule plus placebo as control group. Safety will be monitored throughout the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

1503 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

ATLAS: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of JNJ-56021927 in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Receiving Treatment With Primary Radiation Therapy

Actual Study Start Date :

Nov 19, 2015

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Oct 6, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apalutamide Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.	Drug: Apalutamide Drug: Bicalutamide Placebo Drug: GnRH (agonist) Radiation: 74-80 Grays (units of radiation)
Active Comparator: Control group Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.	Drug: Bicalutamide Drug: Apalutamide Placebo Drug: GnRH (agonist) Radiation: 74-80 Grays (units of radiation)

Arm

Intervention/Treatment

Experimental: Apalutamide

Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

Drug: Apalutamide

Drug: Bicalutamide Placebo

Drug: GnRH (agonist)

Radiation: 74-80 Grays (units of radiation)

Active Comparator: Control group

Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.

Drug: Bicalutamide

Drug: Apalutamide Placebo

Drug: GnRH (agonist)

Radiation: 74-80 Grays (units of radiation)

Outcome Measures

Primary Outcome Measures

Metastasis-free survival [108 Months]
Metastasis-free survival is defined as the time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis based on conventional imaging by blinded independent central review (BICR), histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.

Secondary Outcome Measures

Event-free Survival [108 Months]
Event-free survival is defined as the time from randomization to the date of the first occurrence of prostate specific antigen (PSA) failure by the Phoenix definition, local or regional disease recurrence on conventional imaging by BICR or histopathologic diagnosis, distant metastasis on conventional imaging by BICR or histopathologic diagnosis, or death.
Time to Prostate Specific Antigen (PSA) Progression [108 Months]
Time to PSA progression is defined as time from randomization to the date of PSA nadir plus (+) 0.5 nanograms per milliliter (ng/mL) and rising.
Overall Survival (OS) [108 Months]
OS is defined as the time from randomization to date of death from any cause.
Time to Distant Metastasis [108 Months]
Time to distant metastasis is defined as the time from randomization to the date of the first occurrence of radiographic or pathological bone or soft tissue distant metastasis on conventional imaging by BICR or histopathologic diagnosis of distant metastasis.
Time to Next Local or Systemic Treatment [108 Months]
Time to next local or systemic treatment defined as time from randomization to first subsequent therapy, including re-initiation of androgen deprivation therapy (ADT) and local treatments for local-regional recurrence or distant metastasis.
MFS by Conventional or Positron Emission Tomography (PET) Imaging [108 Months]
MFS by conventional or PET imaging is defined as time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis based on conventional imaging or PET imaging, histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >= 18 years
Indicated and planned to receive primary radiation therapy for prostate cancer
Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following at diagnosis: 1) Gleason score >=8 and >=cT2c, 2) Gleason score >=7, PSA >=20 nanogram per milliliters (ng/mL), and >=cT2c
Charlson index (CCI) <=3
An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1
Adequate organ function: (1) aspartate aminotransferase (AST), alanine aminotransferase (ALT), within normal limits (WNL), (2) serum creatinine less than (<) 1.5 milligram/deciliter (mg/dL) (<133 micromoles/Liter [mcmol/L]), (3) platelets greater than or equal to (>=)140,000/microLiter (mcL), independent of transfusion and/or growth factors within 3 months prior to randomization, (4) Hemoglobin >= 12.0 gram/deciliter (g/dL) (7.4 millimloes [mmol], independent of transfusion and/or growth factors within 3 months prior to randomization
Participants who are sexually active (even men with vasectomies) and willing to use a condom and agree not to donate sperm during the trial
Signed, written, informed consent
Be able to swallow whole study drug tablets

Exclusion Criteria: -

Presence of distant metastasis, (clinical stage M1). Isolated pelvic nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0.
Prior treatment with gonadotropin releasing hormone (GnRH) analogue or anti-androgen or both for >3 months prior to randomization
Bilateral orchiectomy
History of pelvic radiation
Prior systemic (example [e.g.], chemotherapy) or local (e.g. radical prostatectomy, cryotherapy) treatment for prostate cancer
History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness <= 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer
Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-T) for prostate cancer
Prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
Use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) <=4 weeks prior to randomization
Use of any investigational agent <=4 weeks prior to randomization
Current chronic use of opioid analgesics for >=3 weeks for oral or >7 days for non-oral formulations
Major surgery <=4 weeks prior to randomization
Current or prior treatment with anti-epileptic medications for the treatment of seizures
Gastrointestinal conditions affecting absorption
Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or GnRH agonists or any of the components of the formulations
Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject

Contacts and Locations

Locations

	City	State	Country
1	Homewood	Alabama	United States
2	Chandler	Arizona	United States
3	Scottsdale	Arizona	United States
4	Tucson	Arizona	United States
5	Bakersfield	California	United States
6	Los Angeles	California	United States
7	Orange	California	United States
8	San Bernardino	California	United States
9	San Diego	California	United States
10	San Francisco	California	United States
11	Aurora	Colorado	United States
12	Denver	Colorado	United States
13	Middlebury	Connecticut	United States
14	Bradenton	Florida	United States
15	Daytona Beach	Florida	United States
16	Fort Myers	Florida	United States
17	Hialeah	Florida	United States
18	Lakewood Ranch	Florida	United States
19	Naples	Florida	United States
20	Plantation	Florida	United States
21	Meridian	Idaho	United States
22	Evergreen Park	Illinois	United States
23	Harvey	Illinois	United States
24	Jeffersonville	Indiana	United States
25	Wichita	Kansas	United States
26	Ashland	Kentucky	United States
27	New Orleans	Louisiana	United States
28	Shreveport	Louisiana	United States
29	Scarborough	Maine	United States
30	Baltimore	Maryland	United States
31	Boston	Massachusetts	United States
32	Saint Louis	Missouri	United States
33	Morristown	New Jersey	United States
34	Albany	New York	United States
35	Bronx	New York	United States
36	Brooklyn	New York	United States
37	New York	New York	United States
38	Poughkeepsie	New York	United States
39	Rochester	New York	United States
40	Syracuse	New York	United States
41	Cary	North Carolina	United States
42	Raleigh	North Carolina	United States
43	Portland	Oregon	United States
44	Springfield	Oregon	United States
45	Bala-Cynwyd	Pennsylvania	United States
46	Bryn Mawr	Pennsylvania	United States
47	Lancaster	Pennsylvania	United States
48	Philadelphia	Pennsylvania	United States
49	Warwick	Rhode Island	United States
50	Charleston	South Carolina	United States
51	Myrtle Beach	South Carolina	United States
52	Nashville	Tennessee	United States
53	Dallas	Texas	United States
54	Houston	Texas	United States
55	San Antonio	Texas	United States
56	Fairfax	Virginia	United States
57	Virginia Beach	Virginia	United States
58	Burien	Washington	United States
59	Spokane	Washington	United States
60	Morgantown	West Virginia	United States
61	C.a.b.a.		Argentina
62	Caba		Argentina
63	Ciudad Autonoma de Buenos Aires		Argentina
64	Ciudad Autónoma de Buenos Aires		Argentina
65	Pergamino		Argentina
66	Rosario		Argentina
67	San Salvador De Jujuy		Argentina
68	Aalst		Belgium
69	Bonheiden		Belgium
70	Brussel		Belgium
71	Haine-St-Paul		Belgium
72	Leuven		Belgium
73	Liège		Belgium
74	Namur		Belgium
75	Roeselare		Belgium
76	Sint-Niklaas		Belgium
77	Turnhout		Belgium
78	Wilrijk		Belgium
79	Barretos		Brazil
80	Belo Horizonte		Brazil
81	Campinas		Brazil
82	Curitiba		Brazil
83	Florianópolis		Brazil
84	Goiânia		Brazil
85	Ijui		Brazil
86	Natal		Brazil
87	Porto Alegre		Brazil
88	Ribeirao Preto		Brazil
89	Rio de Janeiro		Brazil
90	Salvador		Brazil
91	Santo André		Brazil
92	Sao Jose do Rio Preto		Brazil
93	Sao Paulo		Brazil
94	Sorocaba		Brazil
95	São Paulo		Brazil
96	Calgary	Alberta	Canada
97	Surrey	British Columbia	Canada
98	Vancouver	British Columbia	Canada
99	Victoria	British Columbia	Canada
100	London	Ontario	Canada
101	Ottawa	Ontario	Canada
102	Toronto	Ontario	Canada
103	Gatineau	Quebec	Canada
104	Laval	Quebec	Canada
105	Montreal	Quebec	Canada
106	Montréal	Quebec	Canada
107	Sherbrooke	Quebec	Canada
108	Quebec		Canada
109	Beijing		China
110	ChengDu		China
111	ChongQing		China
112	GuangZhou		China
113	Hangzhou		China
114	Nanchang		China
115	NanJing		China
116	Ningbo		China
117	ShangHai		China
118	Wuhan		China
119	Xi'An		China
120	Hradec Králove		Czechia
121	Liberec		Czechia
122	Nový Jicin		Czechia
123	Olomouc		Czechia
124	Opava		Czechia
125	Pardubice		Czechia
126	Praha 10		Czechia
127	Praha 2		Czechia
128	Praha 4		Czechia
129	Praha 5		Czechia
130	Praha 8		Czechia
131	Zlin		Czechia
132	Amiens		France
133	Angers Cedex 02		France
134	Avignon Cedex 9		France
135	Bayonne		France
136	Besancon		France
137	Bordeaux		France
138	Brest		France
139	Dijon		France
140	Hyères		France
141	La Tronche		France
142	Le Mans		France
143	Lille		France
144	Marseille cedex 05		France
145	Marseilli		France
146	Montpellier		France
147	Neuilly-sur-Seine		France
148	Paris		France
149	Ris Orangis		France
150	Saint Herblain		France
151	Saint-Brieuc		France
152	Saint-Mandé		France
153	Saint-Priest-en-Jarez		France
154	Strasbourg		France
155	Toulouse		France
156	Tours		France
157	Vandoeuvre-les-Nancy		France
158	Villejuif Cedex		France
159	Braunschweig		Germany
160	Chemnitz		Germany
161	Dessau		Germany
162	Frankfurt		Germany
163	Gronau		Germany
164	Jena		Germany
165	Münster		Germany
166	Nürtingen		Germany
167	Ulm		Germany
168	Weiden		Germany
169	Beer Yaakov		Israel
170	Beer-Sheva		Israel
171	Haifa		Israel
172	Jerusalem		Israel
173	Kfar Saba		Israel
174	Petach-Tikva		Israel
175	Ramat-Gan		Israel
176	Tel-Aviv		Israel
177	Daegu		Korea, Republic of
178	Gyeonggi-do		Korea, Republic of
179	Jeollanam-do		Korea, Republic of
180	Seoul		Korea, Republic of
181	Georgetown		Malaysia
182	Kuala Lumpur		Malaysia
183	Kuching		Malaysia
184	Putrajaya		Malaysia
185	Culiacan		Mexico
186	Guadalajara		Mexico
187	Leon		Mexico
188	Mexico		Mexico
189	Morelia		Mexico
190	Zapopan		Mexico
191	Alkmaar		Netherlands
192	Amsterdam		Netherlands
193	Den Haag		Netherlands
194	Nijmegen		Netherlands
195	Rotterdam		Netherlands
196	Bialystok		Poland
197	Bydgoszcz		Poland
198	Gdynia		Poland
199	Gliwice		Poland
200	Kielce		Poland
201	Lodz		Poland
202	Olsztyn		Poland
203	Poznan		Poland
204	Walbrzych		Poland
205	Bucuresti		Romania
206	Cluj-Napoca		Romania
207	Floresti		Romania
208	Iasi		Romania
209	Otopeni		Romania
210	Ploiesti		Romania
211	Sibiu		Romania
212	Targu Mures		Romania
213	Timisoara		Romania
214	Barnaul		Russian Federation
215	Ivanovo		Russian Federation
216	Moscow		Russian Federation
217	Nizhny Novgorod		Russian Federation
218	Obninsk		Russian Federation
219	Omsk		Russian Federation
220	Pyatigorsk		Russian Federation
221	Rostov-on-Don		Russian Federation
222	Ryazan		Russian Federation
223	Saint Petersburg		Russian Federation
224	Saint-Petersburg		Russian Federation
225	Saransk		Russian Federation
226	St Petersburg		Russian Federation
227	Tambov		Russian Federation
228	Tyumen		Russian Federation
229	Ufa		Russian Federation
230	Vologda		Russian Federation
231	Barakaldo		Spain
232	Barcelona		Spain
233	Castellon		Spain
234	Hospitalet de Llobregat		Spain
235	Las Palmas de Gran Canaria		Spain
236	Madrid		Spain
237	Málaga		Spain
238	Reus		Spain
239	Santiago de Compostela		Spain
240	Sevilla		Spain
241	Stockholm		Sweden
242	Umeå		Sweden
243	Örebro		Sweden
244	Kaohsiung		Taiwan
245	Taichung		Taiwan
246	Tainan		Taiwan
247	Taipei City		Taiwan
248	Taipei		Taiwan
249	Taoyuan		Taiwan
250	Adana		Turkey
251	Ankara		Turkey
252	Edirne		Turkey
253	Istanbul		Turkey
254	Izmir		Turkey
255	Kayseri		Turkey
256	Kocaeli		Turkey
257	Dnipro		Ukraine
258	Khakhiv		Ukraine
259	Kyiv		Ukraine
260	Lviv		Ukraine
261	Aberdeen		United Kingdom
262	Birmingham		United Kingdom
263	Bristol		United Kingdom
264	Derby		United Kingdom
265	Glasgow		United Kingdom
266	Oxford		United Kingdom
267	Plymouth		United Kingdom
268	Preston		United Kingdom
269	Sheffield		United Kingdom
270	Sutton		United Kingdom
271	Wolverhampton		United Kingdom