SYNERGY: Comparison of Docetaxel/Prednisone to Docetaxel/Prednisone in Combination With OGX-011 in Men With Prostate Cancer

Sponsor

Achieve Life Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01188187

Collaborator

Teva Branded Pharmaceutical Products R&D, Inc. (Industry)

1,022

Enrollment

140

Locations

Arms

Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase 3 study has been designed to confirm that adding custirsen to standard first-line docetaxel/prednisone treatment can slow tumor progression and enhance survival outcomes compared to standard first-line docetaxel/prednisone treatment alone. This will be a randomized, open-label, multicenter, international trial. Treatment will consist of docetaxel/prednisone/custirsen vs. docetaxel/prednisone. A total of at least 1000 patients will be randomized. Patients will be randomly assigned with equal probability to the two arms.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Custirsen Drug: Docetaxel Drug: Prednisone Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1022 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase 3 Study Comparing Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination With Custirsen (OGX-011) in Men With Metastatic Castrate Resistant Prostate Cancer

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Feb 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Custirsen, Docetaxel, Prednisone Three doses of 640 mg custirsen administered intravenously (IV) as a loading dose between Days -9 to -1. Custirsen, 640 mg, given IV weekly on Days 1, 8, and 15 of each 21-day cycle. Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day and dexamethasone (8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration). Treatment continues for 10 cycles or until unacceptable toxicity or disease progression.	Drug: Custirsen Other Names: OGX-011 Drug: Docetaxel Drug: Prednisone Drug: Dexamethasone Dexamethasone 8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration to reduce the incidence and severity of hypersensitivity reactions and fluid retention.
Active Comparator: Docetaxel, Prednisone Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day and dexamethasone (8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration). Treatment continues for 10 cycles or until unacceptable toxicity or disease progression.	Drug: Docetaxel Drug: Prednisone Drug: Dexamethasone Dexamethasone 8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration to reduce the incidence and severity of hypersensitivity reactions and fluid retention.

Arm

Intervention/Treatment

Experimental: Custirsen, Docetaxel, Prednisone

Three doses of 640 mg custirsen administered intravenously (IV) as a loading dose between Days -9 to -1. Custirsen, 640 mg, given IV weekly on Days 1, 8, and 15 of each 21-day cycle. Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day and dexamethasone (8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration). Treatment continues for 10 cycles or until unacceptable toxicity or disease progression.

Drug: Custirsen

Other Names:

OGX-011

Drug: Docetaxel

Drug: Prednisone

Drug: Dexamethasone

Dexamethasone 8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration to reduce the incidence and severity of hypersensitivity reactions and fluid retention.

Active Comparator: Docetaxel, Prednisone

Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day and dexamethasone (8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration). Treatment continues for 10 cycles or until unacceptable toxicity or disease progression.

Drug: Docetaxel

Drug: Prednisone

Drug: Dexamethasone

Dexamethasone 8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration to reduce the incidence and severity of hypersensitivity reactions and fluid retention.

Outcome Measures

Primary Outcome Measures

Kaplan-Meier Estimates for Time to Death (Overall Survival) [Randomization (approximately Day -12) to longest survival follow-up (Day 971).]
Time from the date of randomization to death from any cause. After stopping treatment, patients were followed every 4 weeks until disease progression and then followed every 12 weeks until death.

Secondary Outcome Measures

Percentage of Participants Who Were Alive Without Event At Day 140 [Day 125-155]
Patients who were alive without event (AWE) are patients who had their Milestone Day 140 Disease Status performed per protocol (Day 125 - Day 155 window), were not determined to have disease progression by the investigator on that window and confirmed as not having progressive disease (NONPD) by the Central Imagine Lab independent review.
Percentage of Participants with Adverse Events [Docetaxel/prednisone/custirsen arm: Days -9 up to Day 743. Docetaxel/prednisone arm: Day 1 up to Day 400.]
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the administration, at any dose, of a medicinal or therapeutic product whether or not considered related to that product. Severity was rated by the investigator on a scale of 1 (mild) to 5 (death). A severity of 3 = Severe or medically significant but not immediately life-threatening. A severity of 4 = Life-threatening. Serious AEs include death (death due to progressive disease were not reported as an SAE), a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria

Age ≥ 18 years on the date of consent.
Histological or cytological diagnosis of adenocarcinoma of the prostate.
Metastatic disease on chest, abdominal, or pelvic CT and/or bone scan.
Systemic chemotherapy indicated due to progression while on or after androgen ablative therapy defined as:

Progressive measurable disease: at least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed -or- the appearance of one or more new lesions as assessed by CT scan during hormone ablation treatment. Measurable lesions are nodal or visceral soft-tissue lesions with nodal lesions ≥ 20 mm in diameter or visceral/soft-tissue lesions ≥ 10 mm in diameter (see Section 6.3.1.1 ).

Bone Scan Progression: appearance of 2 or more new lesions on bone scan during hormone ablation treatment.

Increasing serum prostate-specific antigen (PSA) level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. A minimum starting value of 5.0 ng/mL is required for study randomization.

Baseline laboratory values as stated below:

Creatinine ≤ 1.5 x upper limit of normal (ULN).
Bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's disease).
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) ≤ 1.5 x ULN.
Castrate serum testosterone level (< 50 ng/dL-or-< 1.7 nmol/L).

Must be willing to continue primary androgen suppression with gonadotropin-releasing hormone (GnRH) analogues (either agonists or antagonists) throughout the study, unless treated with bilateral orchiectomy.
Adequate bone marrow function defined at screening as absolute neutrophil count (ANC) ≥ 1.5 x 10^{9 cells /L and platelet count ≥ 100 x 10}9 /L.
Karnofsky score ≥ 70% (see Appendix 17.2).
At least 28 days has passed since completing radiotherapy (exception for radiotherapy: at least 7 days since completing a single fraction of ≤ 800 centigray (cGy) to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of randomization.
At least 4 weeks have passed since receiving any investigational agent at the time of randomization.
Has recovered from any other therapy-related toxicity to ≤ grade 2, (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy).
Patient must be willing to not add, delete or change their current bisphosphonate or denosumab usage throughout study treatment to assure that adverse event reporting is not confounded by changing their bisphosphonate or denosumab usage (unless withdrawn or changed as a result of bisphosphonate or denosumab associated toxicity).
Patients receiving more than 10 mg of prednisone per day (or steroid equivalent) at screening must be willing to have the dose reduced to 10 mg of prednisone per day for at least 7 days prior to randomization and maintained throughout study treatment.
Written informed consent must be obtained prior to any protocol-specific procedures being performed.

Exclusion Criteria

Received any other cytotoxic chemotherapy as treatment for prostate cancer.
Received any cycling, intermittent or continuous hormonal treatment 28 days prior to randomization with the exception of the continuous GnRH analogues required in Inclusion Criteria #6.
Participated in a prior clinical study evaluating custirsen.
History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. (Brain imaging for asymptomatic patients is not required.)
Current symptomatic cord compression requiring surgery or radiation therapy. (Once successfully treated and there has been no progression, patients are eligible for the study.) -Active second malignancy (except non-melanomatous skin or superficial bladder cancer) defined as requiring anticancer therapy or at high risk of recurrence during the study.
Active second malignancy (except non melanomatous skin or superficial bladder cancer) defined as requiring cancer therapy or at high risk of reoccurrence during the study
Uncontrolled medical conditions such as heart failure, myocardial infarction, uncontrolled hypertension, stroke or treatment of a major active infection within 3 months of randomization, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.
Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.

Contacts and Locations

Locations

	Site	City	State	Country
1	Teva Investigational Site 100	Birmingham	Alabama	United States
2	Teva Investigational Site 086	Los Angeles	California	United States
3	Teva Investigational Site 263	Los Angeles	California	United States
4	Teva Investigational Site 093	Marina del Rey	California	United States
5	Teva Investigational Site 097	San Diego	California	United States
6	Teva Investigational Site 090	Fort Collins	Colorado	United States
7	Teva Investigational Site 106	Fort Myers	Florida	United States
8	Teva Investigational Site 094	Port St. Lucie	Florida	United States
9	Teva Investigational Site 096	Atlanta	Georgia	United States
10	Teva Investigational Site 103	Baton Rough	Louisiana	United States
11	Teva Investigational Site 098	Ann Arbor	Michigan	United States
12	Teva Investigational Site 112	Detroit	Michigan	United States
13	Teva Investigational Site 032	Rochester	Minnesota	United States
14	Teva Investigational Site 204	Las Vegas	Nevada	United States
15	Teva Investigational Site 107	Cincinnati	Ohio	United States
16	Teva Investigational Site 266	Greensboro	South Carolina	United States
17	Teva Investigational Site 102	Myrtle Beach	South Carolina	United States
18	Teva Investigational Site 084	Memphis	Tennessee	United States
19	Teva Investigational Site 101	Nashville	Tennessee	United States
20	Teva Investigational Site 116	San Antonio	Texas	United States
21	Teva Investigational Site 059	Tyler	Texas	United States
22	Teva Investigational Site 063	Tyler	Texas	United States
23	Teva Investigational Site 047	Newport	Virginia	United States
24	Teva Investigational Site 104	Norfolk	Virginia	United States
25	Teva Investigational Site 029	Seattle	Washington	United States
26	Teva Investigational Site 862	Bonheiden		Belgium
27	Teva Investigational Site 860	Brussels		Belgium
28	Teva Investigational Site 864	Edegem		Belgium
29	Teva Investigational Site 863	Gent		Belgium
30	Teva Investigational Site 002	Calgary	Alberta	Canada
31	Teva Investigational Site 023	Edmonton	Alberta	Canada
32	Teva Investigational Site 118	Abbotsford	British Columbia	Canada
33	Teva Investigational Site 007	Surrey	British Columbia	Canada
34	Teva Investigational Site 001	Vancouver	British Columbia	Canada
35	Teva Investigational Site 085	Victoria	British Columbia	Canada
36	Teva Investigational Site 024	Winnipeg	Manitoba	Canada
37	Teva Investigational Site 028	Halifax	Nova Scotia	Canada
38	Teva Investigational Site 025	Hamilton	Ontario	Canada
39	Teva Investigational Site 108	Kingston	Ontario	Canada
40	Teva Investigational Site 091	Oshawa	Ontario	Canada
41	Teva Investigational Site 003	Ottawa	Ontario	Canada
42	Teva Investigational Site 004	Toronto	Ontario	Canada
43	Teva Investigational Site 087	Toronto	Ontario	Canada
44	Teva Investigational Site 026	Montreal	Quebec	Canada
45	Teva Investigational Site 027	Montreal	Quebec	Canada
46	Teva Investigational Site 551	Angers Cedex 9		France
47	Teva Investigational Site 552	Avignon		France
48	Teva Investigational Site 553	Grenoble		France
49	Teva Investigational Site 555	La Roche-sur-Yon Cedex		France
50	Teva Investigational Site 557	Marseille		France
51	Teva Investigational Site 558	Nice Cedex 2		France
52	Teva Investigational Site 560	Paris Cedex 05		France
53	Teva Investigational Site 559	Paris Cedex 15		France
54	Teva Investigational Site 561	Saint Herblain Cedex		France
55	Teva Investigational Site 566	Saint-Brieuc Cedex		France
56	Teva Investigational Site 562	Saint-Priest-en-Jarez Cedex		France
57	Teva Investigational Site 563	Toulouse		France
58	Teva Investigational Site 564	Vandoeuvre-les-Nancy Cedex		France
59	Teva Investigational Site 550	Villejuif		France
60	Teva Investigational Site 607	Aachen		Germany
61	Teva Investigational Site 609	Berlin		Germany
62	Teva Investigational Site 613	Berlin		Germany
63	Teva Investigational Site 604	Darmstadt		Germany
64	Teva Investigational Site 612	Dresden		Germany
65	Teva Investigational Site 618	Greifswald		Germany
66	Teva Investigational Site 600	Hannover		Germany
67	Teva Investigational Site 606	Heidelberg		Germany
68	Teva Investigational Site 615	Heinsberg		Germany
69	Teva Investigational Site 611	Homburg/Saar		Germany
70	Teva Investigational Site 617	Kempen		Germany
71	Teva Investigational Site 608	Marburg		Germany
72	Teva Investigational Site 616	Meiningen		Germany
73	Teva Investigational Site 614	Muenchen		Germany
74	Teva Investigational Site 601	Muenster		Germany
75	Teva Investigational Site 602	Nuertingen		Germany
76	Teva Investigational Site 603	Stuttgart		Germany
77	Teva Investigational Site 610	Tuebingen		Germany
78	Teva Investigational Site 605	Wuppertal		Germany
79	Teva Investigational Site 691	Budapest		Hungary
80	Teva Investigational Site 694	Budapest		Hungary
81	Teva Investigational Site 692	Debrecen		Hungary
82	Teva Investigational Site 697	Debrecen		Hungary
83	Teva Investigational Site 696	Gyor		Hungary
84	Teva Investigational Site 698	Miskolc		Hungary
85	Teva Investigational Site 699	Nyiregyhaza		Hungary
86	Teva Investigational Site 693	Szeged		Hungary
87	Teva Investigational Site 695	Veszprem		Hungary
88	Teva Investigational Site 506	Jerusalem	IL	Israel
89	Teva Investigational Site 507	Haifa		Israel
90	Teva Investigational Site 505	Petach Tikva		Israel
91	Teva Investigational Site 502	Ramat Gan		Israel
92	Teva Investigational Site 503	Tel Aviv		Israel
93	Teva Investigational Site 501	Zrifin		Israel
94	Teva Investigational Site 753	Arezzo		Italy
95	Teva Investigational Site 758	Catanzaro		Italy
96	Teva Investigational Site 760	Cesena (FC)		Italy
97	Teva Investigational Site 752	Genova		Italy
98	Teva Investigational Site 755	Lugo (Ravenna)		Italy
99	Teva Investigational Site 759	Meldola (FC)		Italy
100	Teva Investigational Site 763	Milano		Italy
101	Teva Investigational Site 754	Napoli		Italy
102	Teva Investigational Site 756	Napoli		Italy
103	Teva Investigational Site 761	Rimini		Italy
104	Teva Investigational Site 750	Roma		Italy
105	Teva Investigational Site 762	Roma		Italy
106	Teva Investigational Site 764	Rozzano (MI)		Italy
107	Teva Investigational Site 765	Verona		Italy
108	Teva Investigational Site 404	Cheongju,Chungbuk		Korea, Republic of
109	Teva Investigational Site 401	Goyang-si Gyeonggi-do		Korea, Republic of
110	Teva Investigational Site 400	Seoul		Korea, Republic of
111	Teva Investigational Site 402	Seoul		Korea, Republic of
112	Teva Investigational Site 403	Seoul		Korea, Republic of
113	Teva Investigational Site 406	Seoul		Korea, Republic of
114	Teva Investigational Site 405	Yangsan-si		Korea, Republic of
115	Teva Investigational Site 851	Amsterdam		Netherlands
116	Teva Investigational Site 852	Rotterdam		Netherlands
117	Teva Investigational Site 853	Sittard-Geleen		Netherlands
118	Teva Investigational Site 803	Barcelona		Spain
119	Teva Investigational Site 808	Barcelona		Spain
120	Teva Investigational Site 809	Barcelona		Spain
121	Teva Investigational Site 816	Dos Hermanas		Spain
122	Teva Investigational Site 814	El Palmar		Spain
123	Teva Investigational Site 807	Guadalajara		Spain
124	Teva Investigational Site 800	Madrid		Spain
125	Teva Investigational Site 801	Madrid		Spain
126	Teva Investigational Site 806	Madrid		Spain
127	Teva Investigational Site 813	Madrid		Spain
128	Teva Investigational Site 815	Manresa		Spain
129	Teva Investigational Site 810	Murcia		Spain
130	Teva Investigational Site 811	Palma de Mallorca		Spain
131	Teva Investigational Site 805	Pamplona		Spain
132	Teva Investigational Site 804	Sabadell - Barcelona		Spain
133	Teva Investigational Site 802	Valencia		Spain
134	Teva Investigational Site 704	Brighton		United Kingdom
135	Teva Investigational Site 701	Cambridge		United Kingdom
136	Teva Investigational Site 709	Coventry		United Kingdom
137	Teva Investigational Site 705	Guildford, Surrey		United Kingdom
138	Teva Investigational Site 703	Manchester		United Kingdom
139	Teva Investigational Site 700	Surrey		United Kingdom
140	Teva Investigational Site 710	Wirral		United Kingdom