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

Prostate Cancer Clinical Trial

— SYNERGY  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01188187
• Other study ID #: OGX-011-11 TRANSFERRED
• Status: Completed
• Phase: Phase 3
• First received: August 23, 2010
• Last updated: October 13, 2016
• Start date: November 2010
• Est. completion date: June 2014

Study information

• Verified date: October 2016
• Source: OncoGenex Technologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1022
• Est. completion date: June 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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:

1. 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 ).

OR

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

OR

3. 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:

1. Creatinine = 1.5 x upper limit of normal (ULN).

2. Bilirubin = 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's disease).

3. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) = 1.5 x ULN.

4. 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Custirsen

• Docetaxel

• Prednisone

• 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.

Locations

Country	Name	City	State
Belgium	Teva Investigational Site 862	Bonheiden
Belgium	Teva Investigational Site 860	Brussels
Belgium	Teva Investigational Site 864	Edegem
Belgium	Teva Investigational Site 863	Gent
Canada	Teva Investigational Site 118	Abbotsford	British Columbia
Canada	Teva Investigational Site 002	Calgary	Alberta
Canada	Teva Investigational Site 023	Edmonton	Alberta
Canada	Teva Investigational Site 028	Halifax	Nova Scotia
Canada	Teva Investigational Site 025	Hamilton	Ontario
Canada	Teva Investigational Site 108	Kingston	Ontario
Canada	Teva Investigational Site 026	Montreal	Quebec
Canada	Teva Investigational Site 027	Montreal	Quebec
Canada	Teva Investigational Site 091	Oshawa	Ontario
Canada	Teva Investigational Site 003	Ottawa	Ontario
Canada	Teva Investigational Site 007	Surrey	British Columbia
Canada	Teva Investigational Site 004	Toronto	Ontario
Canada	Teva Investigational Site 087	Toronto	Ontario
Canada	Teva Investigational Site 001	Vancouver	British Columbia
Canada	Teva Investigational Site 085	Victoria	British Columbia
Canada	Teva Investigational Site 024	Winnipeg	Manitoba
France	Teva Investigational Site 551	Angers Cedex 9
France	Teva Investigational Site 552	Avignon
France	Teva Investigational Site 553	Grenoble
France	Teva Investigational Site 555	La Roche-sur-Yon Cedex
France	Teva Investigational Site 557	Marseille
France	Teva Investigational Site 558	Nice Cedex 2
France	Teva Investigational Site 560	Paris Cedex 05
France	Teva Investigational Site 559	Paris Cedex 15
France	Teva Investigational Site 561	Saint Herblain Cedex
France	Teva Investigational Site 566	Saint-Brieuc Cedex
France	Teva Investigational Site 562	Saint-Priest-en-Jarez Cedex
France	Teva Investigational Site 563	Toulouse
France	Teva Investigational Site 564	Vandoeuvre-les-Nancy Cedex
France	Teva Investigational Site 550	Villejuif
Germany	Teva Investigational Site 607	Aachen
Germany	Teva Investigational Site 609	Berlin
Germany	Teva Investigational Site 613	Berlin
Germany	Teva Investigational Site 604	Darmstadt
Germany	Teva Investigational Site 612	Dresden
Germany	Teva Investigational Site 618	Greifswald
Germany	Teva Investigational Site 600	Hannover
Germany	Teva Investigational Site 606	Heidelberg
Germany	Teva Investigational Site 615	Heinsberg
Germany	Teva Investigational Site 611	Homburg/Saar
Germany	Teva Investigational Site 617	Kempen
Germany	Teva Investigational Site 608	Marburg
Germany	Teva Investigational Site 616	Meiningen
Germany	Teva Investigational Site 614	Muenchen
Germany	Teva Investigational Site 601	Muenster
Germany	Teva Investigational Site 602	Nuertingen
Germany	Teva Investigational Site 603	Stuttgart
Germany	Teva Investigational Site 610	Tuebingen
Germany	Teva Investigational Site 605	Wuppertal
Hungary	Teva Investigational Site 691	Budapest
Hungary	Teva Investigational Site 694	Budapest
Hungary	Teva Investigational Site 692	Debrecen
Hungary	Teva Investigational Site 697	Debrecen
Hungary	Teva Investigational Site 696	Gyor
Hungary	Teva Investigational Site 698	Miskolc
Hungary	Teva Investigational Site 699	Nyiregyhaza
Hungary	Teva Investigational Site 693	Szeged
Hungary	Teva Investigational Site 695	Veszprem
Israel	Teva Investigational Site 507	Haifa
Israel	Teva Investigational Site 506	Jerusalem	IL
Israel	Teva Investigational Site 505	Petach Tikva
Israel	Teva Investigational Site 502	Ramat Gan
Israel	Teva Investigational Site 503	Tel Aviv
Israel	Teva Investigational Site 501	Zrifin
Italy	Teva Investigational Site 753	Arezzo
Italy	Teva Investigational Site 758	Catanzaro
Italy	Teva Investigational Site 760	Cesena (FC)
Italy	Teva Investigational Site 752	Genova
Italy	Teva Investigational Site 755	Lugo (Ravenna)
Italy	Teva Investigational Site 759	Meldola (FC)
Italy	Teva Investigational Site 763	Milano
Italy	Teva Investigational Site 754	Napoli
Italy	Teva Investigational Site 756	Napoli
Italy	Teva Investigational Site 761	Rimini
Italy	Teva Investigational Site 750	Roma
Italy	Teva Investigational Site 762	Roma
Italy	Teva Investigational Site 764	Rozzano (MI)
Italy	Teva Investigational Site 765	Verona
Korea, Republic of	Teva Investigational Site 404	Cheongju,Chungbuk
Korea, Republic of	Teva Investigational Site 401	Goyang-si Gyeonggi-do
Korea, Republic of	Teva Investigational Site 400	Seoul
Korea, Republic of	Teva Investigational Site 402	Seoul
Korea, Republic of	Teva Investigational Site 403	Seoul
Korea, Republic of	Teva Investigational Site 406	Seoul
Korea, Republic of	Teva Investigational Site 405	Yangsan-si
Netherlands	Teva Investigational Site 851	Amsterdam
Netherlands	Teva Investigational Site 852	Rotterdam
Netherlands	Teva Investigational Site 853	Sittard-Geleen
Spain	Teva Investigational Site 803	Barcelona
Spain	Teva Investigational Site 808	Barcelona
Spain	Teva Investigational Site 809	Barcelona
Spain	Teva Investigational Site 816	Dos Hermanas
Spain	Teva Investigational Site 814	El Palmar
Spain	Teva Investigational Site 807	Guadalajara
Spain	Teva Investigational Site 800	Madrid
Spain	Teva Investigational Site 801	Madrid
Spain	Teva Investigational Site 806	Madrid
Spain	Teva Investigational Site 813	Madrid
Spain	Teva Investigational Site 815	Manresa
Spain	Teva Investigational Site 810	Murcia
Spain	Teva Investigational Site 811	Palma de Mallorca
Spain	Teva Investigational Site 805	Pamplona
Spain	Teva Investigational Site 804	Sabadell - Barcelona
Spain	Teva Investigational Site 802	Valencia
United Kingdom	Teva Investigational Site 704	Brighton
United Kingdom	Teva Investigational Site 701	Cambridge
United Kingdom	Teva Investigational Site 709	Coventry
United Kingdom	Teva Investigational Site 705	Guildford, Surrey
United Kingdom	Teva Investigational Site 703	Manchester
United Kingdom	Teva Investigational Site 700	Surrey
United Kingdom	Teva Investigational Site 710	Wirral
United States	Teva Investigational Site 098	Ann Arbor	Michigan
United States	Teva Investigational Site 096	Atlanta	Georgia
United States	Teva Investigational Site 103	Baton Rough	Louisiana
United States	Teva Investigational Site 100	Birmingham	Alabama
United States	Teva Investigational Site 107	Cincinnati	Ohio
United States	Teva Investigational Site 112	Detroit	Michigan
United States	Teva Investigational Site 090	Fort Collins	Colorado
United States	Teva Investigational Site 106	Fort Myers	Florida
United States	Teva Investigational Site 266	Greensboro	South Carolina
United States	Teva Investigational Site 204	Las Vegas	Nevada
United States	Teva Investigational Site 086	Los Angeles	California
United States	Teva Investigational Site 263	Los Angeles	California
United States	Teva Investigational Site 093	Marina del Rey	California
United States	Teva Investigational Site 084	Memphis	Tennessee
United States	Teva Investigational Site 102	Myrtle Beach	South Carolina
United States	Teva Investigational Site 101	Nashville	Tennessee
United States	Teva Investigational Site 047	Newport	Virginia
United States	Teva Investigational Site 104	Norfolk	Virginia
United States	Teva Investigational Site 094	Port St. Lucie	Florida
United States	Teva Investigational Site 032	Rochester	Minnesota
United States	Teva Investigational Site 116	San Antonio	Texas
United States	Teva Investigational Site 097	San Diego	California
United States	Teva Investigational Site 029	Seattle	Washington
United States	Teva Investigational Site 059	Tyler	Texas
United States	Teva Investigational Site 063	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
OncoGenex Technologies	Teva Pharmaceutical Industries

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimates for Time to Death (Overall Survival)	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.	Randomization (approximately Day -12) to longest survival follow-up (Day 971).	No
Secondary	Percentage of Participants Who Were Alive Without Event At Day 140	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.	Day 125-155	No
Secondary	Percentage of Participants with Adverse Events	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.	Docetaxel/prednisone/custirsen arm: Days -9 up to Day 743. Docetaxel/prednisone arm: Day 1 up to Day 400.	No