Clinical trial NCT01188187: Comparison of Docetaxel/Prednisone to Docetaxel/Prednisone in Combination With OGX-011 in Men With Prostate Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: custirsen sodium
prostate cancer
overall survival
Metastatic Castrate Resistant Prostate Cancer
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
Collaborators: name: Teva Branded Pharmaceutical Products R&D, Inc.
First posted: 2010-08-25
Enrollment: 1022
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Kaplan-Meier Estimates for Time to Death (Overall Survival)
timeFrame: Randomization (approximately Day -12) to longest survival follow-up (Day 971).
Secondary outcomes:
measure: Percentage of Participants Who Were Alive Without Event At Day 140
timeFrame: Day 125-155
measure: Percentage of Participants with Adverse Events
timeFrame: Docetaxel/prednisone/custirsen arm: Days -9 up to Day 743. Docetaxel/prednisone arm: Day 1 up to Day 400.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 100
state: Alabama
city: Los Angeles
country: United States
facility: Teva Investigational Site 086
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 263
state: California
city: Marina del Rey
country: United States
facility: Teva Investigational Site 093
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 097
state: California
city: Fort Collins
country: United States
facility: Teva Investigational Site 090
state: Colorado
city: Fort Myers
country: United States
facility: Teva Investigational Site 106
state: Florida
city: Port St. Lucie
country: United States
facility: Teva Investigational Site 094
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 096
state: Georgia
city: Baton Rough
country: United States
facility: Teva Investigational Site 103
state: Louisiana
city: Ann Arbor
country: United States
facility: Teva Investigational Site 098
state: Michigan
city: Detroit
country: United States
facility: Teva Investigational Site 112
state: Michigan
city: Rochester
country: United States
facility: Teva Investigational Site 032
state: Minnesota
city: Las Vegas
country: United States
facility: Teva Investigational Site 204
state: Nevada
city: Cincinnati
country: United States
facility: Teva Investigational Site 107
state: Ohio
city: Greensboro
country: United States
facility: Teva Investigational Site 266
state: South Carolina
city: Myrtle Beach
country: United States
facility: Teva Investigational Site 102
state: South Carolina
city: Memphis
country: United States
facility: Teva Investigational Site 084
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 101
state: Tennessee
city: San Antonio
country: United States
facility: Teva Investigational Site 116
state: Texas
city: Tyler
country: United States
facility: Teva Investigational Site 059
state: Texas
city: Tyler
country: United States
facility: Teva Investigational Site 063
state: Texas
city: Newport
country: United States
facility: Teva Investigational Site 047
state: Virginia
city: Norfolk
country: United States
facility: Teva Investigational Site 104
state: Virginia
city: Seattle
country: United States
facility: Teva Investigational Site 029
state: Washington
city: Bonheiden
country: Belgium
facility: Teva Investigational Site 862
city: Brussels
country: Belgium
facility: Teva Investigational Site 860
city: Edegem
country: Belgium
facility: Teva Investigational Site 864
city: Gent
country: Belgium
facility: Teva Investigational Site 863
city: Calgary
country: Canada
facility: Teva Investigational Site 002
state: Alberta
city: Edmonton
country: Canada
facility: Teva Investigational Site 023
state: Alberta
city: Abbotsford
country: Canada
facility: Teva Investigational Site 118
state: British Columbia
city: Surrey
country: Canada
facility: Teva Investigational Site 007
state: British Columbia
city: Vancouver
country: Canada
facility: Teva Investigational Site 001
state: British Columbia
city: Victoria
country: Canada
facility: Teva Investigational Site 085
state: British Columbia
city: Winnipeg
country: Canada
facility: Teva Investigational Site 024
state: Manitoba
city: Halifax
country: Canada
facility: Teva Investigational Site 028
state: Nova Scotia
city: Hamilton
country: Canada
facility: Teva Investigational Site 025
state: Ontario
city: Kingston
country: Canada
facility: Teva Investigational Site 108
state: Ontario
city: Oshawa
country: Canada
facility: Teva Investigational Site 091
state: Ontario
city: Ottawa
country: Canada
facility: Teva Investigational Site 003
state: Ontario
city: Toronto
country: Canada
facility: Teva Investigational Site 004
state: Ontario
city: Toronto
country: Canada
facility: Teva Investigational Site 087
state: Ontario
city: Montreal
country: Canada
facility: Teva Investigational Site 026
state: Quebec
city: Montreal
country: Canada
facility: Teva Investigational Site 027
state: Quebec
city: Angers Cedex 9
country: France
facility: Teva Investigational Site 551
city: Avignon
country: France
facility: Teva Investigational Site 552
city: Grenoble
country: France
facility: Teva Investigational Site 553
city: La Roche-sur-Yon Cedex
country: France
facility: Teva Investigational Site 555
city: Marseille
country: France
facility: Teva Investigational Site 557
city: Nice Cedex 2
country: France
facility: Teva Investigational Site 558
city: Paris Cedex 05
country: France
facility: Teva Investigational Site 560
city: Paris Cedex 15
country: France
facility: Teva Investigational Site 559
city: Saint Herblain Cedex
country: France
facility: Teva Investigational Site 561
city: Saint-Brieuc Cedex
country: France
facility: Teva Investigational Site 566
city: Saint-Priest-en-Jarez Cedex
country: France
facility: Teva Investigational Site 562
city: Toulouse
country: France
facility: Teva Investigational Site 563
city: Vandoeuvre-les-Nancy Cedex
country: France
facility: Teva Investigational Site 564
city: Villejuif
country: France
facility: Teva Investigational Site 550
city: Aachen
country: Germany
facility: Teva Investigational Site 607
city: Berlin
country: Germany
facility: Teva Investigational Site 609
city: Berlin
country: Germany
facility: Teva Investigational Site 613
city: Darmstadt
country: Germany
facility: Teva Investigational Site 604
city: Dresden
country: Germany
facility: Teva Investigational Site 612
city: Greifswald
country: Germany
facility: Teva Investigational Site 618
city: Hannover
country: Germany
facility: Teva Investigational Site 600
city: Heidelberg
country: Germany
facility: Teva Investigational Site 606
city: Heinsberg
country: Germany
facility: Teva Investigational Site 615
city: Homburg/Saar
country: Germany
facility: Teva Investigational Site 611
city: Kempen
country: Germany
facility: Teva Investigational Site 617
city: Marburg
country: Germany
facility: Teva Investigational Site 608
city: Meiningen
country: Germany
facility: Teva Investigational Site 616
city: Muenchen
country: Germany
facility: Teva Investigational Site 614
city: Muenster
country: Germany
facility: Teva Investigational Site 601
city: Nuertingen
country: Germany
facility: Teva Investigational Site 602
city: Stuttgart
country: Germany
facility: Teva Investigational Site 603
city: Tuebingen
country: Germany
facility: Teva Investigational Site 610
city: Wuppertal
country: Germany
facility: Teva Investigational Site 605
city: Budapest
country: Hungary
facility: Teva Investigational Site 691
city: Budapest
country: Hungary
facility: Teva Investigational Site 694
city: Debrecen
country: Hungary
facility: Teva Investigational Site 692
city: Debrecen
country: Hungary
facility: Teva Investigational Site 697
city: Gyor
country: Hungary
facility: Teva Investigational Site 696
city: Miskolc
country: Hungary
facility: Teva Investigational Site 698
city: Nyiregyhaza
country: Hungary
facility: Teva Investigational Site 699
city: Szeged
country: Hungary
facility: Teva Investigational Site 693
city: Veszprem
country: Hungary
facility: Teva Investigational Site 695
city: Jerusalem
country: Israel
facility: Teva Investigational Site 506
state: IL
city: Haifa
country: Israel
facility: Teva Investigational Site 507
city: Petach Tikva
country: Israel
facility: Teva Investigational Site 505
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 502
city: Tel Aviv
country: Israel
facility: Teva Investigational Site 503
city: Zrifin
country: Israel
facility: Teva Investigational Site 501
city: Arezzo
country: Italy
facility: Teva Investigational Site 753
city: Catanzaro
country: Italy
facility: Teva Investigational Site 758
city: Cesena (FC)
country: Italy
facility: Teva Investigational Site 760
city: Genova
country: Italy
facility: Teva Investigational Site 752
city: Lugo (Ravenna)
country: Italy
facility: Teva Investigational Site 755
city: Meldola (FC)
country: Italy
facility: Teva Investigational Site 759
city: Milano
country: Italy
facility: Teva Investigational Site 763
city: Napoli
country: Italy
facility: Teva Investigational Site 754
city: Napoli
country: Italy
facility: Teva Investigational Site 756
city: Rimini
country: Italy
facility: Teva Investigational Site 761
city: Roma
country: Italy
facility: Teva Investigational Site 750
city: Roma
country: Italy
facility: Teva Investigational Site 762
city: Rozzano (MI)
country: Italy
facility: Teva Investigational Site 764
city: Verona
country: Italy
facility: Teva Investigational Site 765
city: Cheongju,Chungbuk
country: Korea, Republic of
facility: Teva Investigational Site 404
city: Goyang-si Gyeonggi-do
country: Korea, Republic of
facility: Teva Investigational Site 401
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 400
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 402
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 403
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 406
city: Yangsan-si
country: Korea, Republic of
facility: Teva Investigational Site 405
city: Amsterdam
country: Netherlands
facility: Teva Investigational Site 851
city: Rotterdam
country: Netherlands
facility: Teva Investigational Site 852
city: Sittard-Geleen
country: Netherlands
facility: Teva Investigational Site 853
city: Barcelona
country: Spain
facility: Teva Investigational Site 803
city: Barcelona
country: Spain
facility: Teva Investigational Site 808
city: Barcelona
country: Spain
facility: Teva Investigational Site 809
city: Dos Hermanas
country: Spain
facility: Teva Investigational Site 816
city: El Palmar
country: Spain
facility: Teva Investigational Site 814
city: Guadalajara
country: Spain
facility: Teva Investigational Site 807
city: Madrid
country: Spain
facility: Teva Investigational Site 800
city: Madrid
country: Spain
facility: Teva Investigational Site 801
city: Madrid
country: Spain
facility: Teva Investigational Site 806
city: Madrid
country: Spain
facility: Teva Investigational Site 813
city: Manresa
country: Spain
facility: Teva Investigational Site 815
city: Murcia
country: Spain
facility: Teva Investigational Site 810
city: Palma de Mallorca
country: Spain
facility: Teva Investigational Site 811
city: Pamplona
country: Spain
facility: Teva Investigational Site 805
city: Sabadell - Barcelona
country: Spain
facility: Teva Investigational Site 804
city: Valencia
country: Spain
facility: Teva Investigational Site 802
city: Brighton
country: United Kingdom
facility: Teva Investigational Site 704
city: Cambridge
country: United Kingdom
facility: Teva Investigational Site 701
city: Coventry
country: United Kingdom
facility: Teva Investigational Site 709
city: Guildford, Surrey
country: United Kingdom
facility: Teva Investigational Site 705
city: Manchester
country: United Kingdom
facility: Teva Investigational Site 703
city: Surrey
country: United Kingdom
facility: Teva Investigational Site 700
city: Wirral
country: United Kingdom
facility: Teva Investigational Site 710
Study officials:
affiliation: Seattle Cancer Care Alliance, US
name: Celestia Higano, MD
role: STUDY_CHAIR
affiliation: Vancouver Prostate Centre, BC Cancer Agency, Canada
name: Kim Chi, MD
role: STUDY_CHAIR
affiliation: Institute of Cancer Research, UK
name: Johann de Bono, Professor
role: STUDY_CHAIR
References:
citation: Chi KN, Higano CS, Blumenstein B, Ferrero JM, Reeves J, Feyerabend S, Gravis G, Merseburger AS, Stenzl A, Bergman AM, Mukherjee SD, Zalewski P, Saad F, Jacobs C, Gleave M, de Bono JS. Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2017 Apr;18(4):473-485. doi: 10.1016/S1470-2045(17)30168-7. Epub 2017 Mar 8.
citation: de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.