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

NCT01188187 | Completed Phase 3

• 1 other identifier: OGX-011-11 TRANSFERRED
• Study Type: interventional
• Target: 1,022
• Locations: 12 countries
• Sites: 140

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.

Conditions

Prostate Cancer

Keywords

custirsen sodium; prostate cancer; overall survival; Metastatic Castrate Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (2)

• Percentage of Participants Who Were Alive Without Event At Day 140

  Day 125-155

• 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.

Study Arms (2)

Custirsen, Docetaxel, Prednisone

EXPERIMENTAL

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; Drug: Docetaxel; Drug: Prednisone; Drug: Dexamethasone

Docetaxel, Prednisone

ACTIVE COMPARATOR

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

Interventions

Custirsen DRUG

Also known as: OGX-011

Custirsen, Docetaxel, Prednisone

Docetaxel DRUG

Custirsen, Docetaxel, Prednisone; Docetaxel, Prednisone

Prednisone DRUG

Custirsen, Docetaxel, Prednisone; Docetaxel, Prednisone

Dexamethasone DRUG

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.

Custirsen, Docetaxel, Prednisone; Docetaxel, Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Received any other cytotoxic chemotherapy as treatment for prostate cancer.
• 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.

Sponsors & Collaborators

• Achieve Life Sciences: lead
• Teva Branded Pharmaceutical Products R&D, Inc.: collaborator

Study Sites (140)

Teva Investigational Site 100

Birmingham, Alabama, United States

Location

Teva Investigational Site 086

Los Angeles, California, United States

Location

Teva Investigational Site 263

Los Angeles, California, United States

Location

Teva Investigational Site 093

Marina del Rey, California, United States

Location

Teva Investigational Site 097

San Diego, California, United States

Location

Teva Investigational Site 090

Fort Collins, Colorado, United States

Location

Teva Investigational Site 106

Fort Myers, Florida, United States

Location

Teva Investigational Site 094

Port Saint Lucie, Florida, United States

Location

Teva Investigational Site 096

Atlanta, Georgia, United States

Location

Teva Investigational Site 103

Baton Rough, Louisiana, United States

Location

Teva Investigational Site 098

Ann Arbor, Michigan, United States

Location

Teva Investigational Site 112

Detroit, Michigan, United States

Location

Teva Investigational Site 032

Rochester, Minnesota, United States

Location

Teva Investigational Site 204

Las Vegas, Nevada, United States

Location

Teva Investigational Site 107

Cincinnati, Ohio, United States

Location

Teva Investigational Site 266

Greensboro, South Carolina, United States

Location

Teva Investigational Site 102

Myrtle Beach, South Carolina, United States

Location

Teva Investigational Site 084

Memphis, Tennessee, United States

Location

Teva Investigational Site 101

Nashville, Tennessee, United States

Location

Teva Investigational Site 116

San Antonio, Texas, United States

Location

Teva Investigational Site 059

Tyler, Texas, United States

Location

Teva Investigational Site 063

Tyler, Texas, United States

Location

Teva Investigational Site 047

Newport, Virginia, United States

Location

Teva Investigational Site 104

Norfolk, Virginia, United States

Location

Teva Investigational Site 029

Seattle, Washington, United States

Location

Teva Investigational Site 862

Bonheiden, Belgium

Location

Teva Investigational Site 860

Brussels, Belgium

Location

Teva Investigational Site 864

Edegem, Belgium

Location

Teva Investigational Site 863

Ghent, Belgium

Location

Teva Investigational Site 002

Calgary, Alberta, Canada

Location

Teva Investigational Site 023

Edmonton, Alberta, Canada

Location

Teva Investigational Site 118

Abbotsford, British Columbia, Canada

Location

Teva Investigational Site 007

Surrey, British Columbia, Canada

Location

Teva Investigational Site 001

Vancouver, British Columbia, Canada

Location

Teva Investigational Site 085

Victoria, British Columbia, Canada

Location

Teva Investigational Site 024

Winnipeg, Manitoba, Canada

Location

Teva Investigational Site 028

Halifax, Nova Scotia, Canada

Location

Teva Investigational Site 025

Hamilton, Ontario, Canada

Location

Teva Investigational Site 108

Kingston, Ontario, Canada

Location

Teva Investigational Site 091

Oshawa, Ontario, Canada

Location

Teva Investigational Site 003

Ottawa, Ontario, Canada

Location

Teva Investigational Site 004

Toronto, Ontario, Canada

Location

Teva Investigational Site 087

Toronto, Ontario, Canada

Location

Teva Investigational Site 026

Montreal, Quebec, Canada

Location

Teva Investigational Site 027

Montreal, Quebec, Canada

Location

Teva Investigational Site 551

Angers, France

Location

Teva Investigational Site 552

Avignon, France

Location

Teva Investigational Site 553

Grenoble, France

Location

Teva Investigational Site 555

La Roche-sur-Yon, France

Location

Teva Investigational Site 557

Marseille, France

Location

Teva Investigational Site 558

Nice, France

Location

Teva Investigational Site 559

Paris, France

Location

Teva Investigational Site 560

Paris, France

Location

Teva Investigational Site 566

Saint-Brieuc, France

Location

Teva Investigational Site 561

Saint-Herblain, France

Location

Teva Investigational Site 562

Saint-Priest-en-Jarez, France

Location

Teva Investigational Site 563

Toulouse, France

Location

Teva Investigational Site 564

Vandœuvre-lès-Nancy, France

Location

Teva Investigational Site 550

Villejuif, France

Location

Teva Investigational Site 607

Aachen, Germany

Location

Teva Investigational Site 609

Berlin, Germany

Location

Teva Investigational Site 613

Berlin, Germany

Location

Teva Investigational Site 604

Darmstadt, Germany

Location

Teva Investigational Site 612

Dresden, Germany

Location

Teva Investigational Site 618

Greifswald, Germany

Location

Teva Investigational Site 600

Hanover, Germany

Location

Teva Investigational Site 606

Heidelberg, Germany

Location

Teva Investigational Site 615

Heinsberg, Germany

Location

Teva Investigational Site 611

Homburg/Saar, Germany

Location

Teva Investigational Site 617

Kempen, Germany

Location

Teva Investigational Site 608

Marburg, Germany

Location

Teva Investigational Site 616

Meiningen, Germany

Location

Teva Investigational Site 614

München, Germany

Location

Teva Investigational Site 601

Münster, Germany

Location

Teva Investigational Site 602

Nürtingen, Germany

Location

Teva Investigational Site 603

Stuttgart, Germany

Location

Teva Investigational Site 610

Tübingen, Germany

Location

Teva Investigational Site 605

Wuppertal, Germany

Location

Teva Investigational Site 691

Budapest, Hungary

Location

Teva Investigational Site 694

Budapest, Hungary

Location

Teva Investigational Site 692

Debrecen, Hungary

Location

Teva Investigational Site 697

Debrecen, Hungary

Location

Teva Investigational Site 696

Győr, Hungary

Location

Teva Investigational Site 698

Miskolc, Hungary

Location

Teva Investigational Site 699

Nyíregyháza, Hungary

Location

Teva Investigational Site 693

Szeged, Hungary

Location

Teva Investigational Site 695

Veszprém, Hungary

Location

Teva Investigational Site 506

Jerusalem, IL, Israel

Location

Teva Investigational Site 507

Haifa, Israel

Location

Teva Investigational Site 505

Petah Tikva, Israel

Location

Teva Investigational Site 502

Ramat Gan, Israel

Location

Teva Investigational Site 503

Tel Aviv, Israel

Location

Teva Investigational Site 501

Zrifin, Israel

Location

Teva Investigational Site 753

Arezzo, Italy

Location

Teva Investigational Site 758

Catanzaro, Italy

Location

Teva Investigational Site 760

Cesena (FC), Italy

Location

Teva Investigational Site 752

Genova, Italy

Location

Teva Investigational Site 755

Lugo (Ravenna), Italy

Location

Teva Investigational Site 759

Meldola (FC), Italy

Location

Teva Investigational Site 763

Milan, Italy

Location

Teva Investigational Site 754

Napoli, Italy

Location

Teva Investigational Site 756

Napoli, Italy

Location

Teva Investigational Site 761

Rimini, Italy

Location

Teva Investigational Site 750

Roma, Italy

Location

Teva Investigational Site 762

Roma, Italy

Location

Teva Investigational Site 764

Rozzano (MI), Italy

Location

Teva Investigational Site 765

Verona, Italy

Location

Teva Investigational Site 851

Amsterdam, Netherlands

Location

Teva Investigational Site 852

Rotterdam, Netherlands

Location

Teva Investigational Site 853

Sittard-Geleen, Netherlands

Location

Teva Investigational Site 404

Cheongju,Chungbuk, South Korea

Location

Teva Investigational Site 401

Goyang-si Gyeonggi-do, South Korea

Location

Teva Investigational Site 400

Seoul, South Korea

Location

Teva Investigational Site 402

Seoul, South Korea

Location

Teva Investigational Site 403

Seoul, South Korea

Location

Teva Investigational Site 406

Seoul, South Korea

Location

Teva Investigational Site 405

Yangsan, South Korea

Location

Teva Investigational Site 803

Barcelona, Spain

Location

Teva Investigational Site 808

Barcelona, Spain

Location

Teva Investigational Site 809

Barcelona, Spain

Location

Teva Investigational Site 816

Dos Hermanas, Spain

Location

Teva Investigational Site 814

El Palmar, Spain

Location

Teva Investigational Site 807

Guadalajara, Spain

Location

Teva Investigational Site 800

Madrid, Spain

Location

Teva Investigational Site 801

Madrid, Spain

Location

Teva Investigational Site 806

Madrid, Spain

Location

Teva Investigational Site 813

Madrid, Spain

Location

Teva Investigational Site 815

Manresa, Spain

Location

Teva Investigational Site 810

Murcia, Spain

Location

Teva Investigational Site 811

Palma de Mallorca, Spain

Location

Teva Investigational Site 805

Pamplona, Spain

Location

Teva Investigational Site 804

Sabadell - Barcelona, Spain

Location

Teva Investigational Site 802

Valencia, Spain

Location

Teva Investigational Site 704

Brighton, United Kingdom

Location

Teva Investigational Site 701

Cambridge, United Kingdom

Location

Teva Investigational Site 709

Coventry, United Kingdom

Location

Teva Investigational Site 705

Guildford, Surrey, United Kingdom

Location

Teva Investigational Site 703

Manchester, United Kingdom

Location

Teva Investigational Site 710

Metropolitan Borough of Wirral, United Kingdom

Location

Teva Investigational Site 700

Surrey, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28283282 DERIVED

• 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.

  PMID: 24722180 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

OGX-011; Docetaxel; Prednisone; Dexamethasone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Steroids, Fluorinated

Study Officials

• Celestia Higano, MD

  Seattle Cancer Care Alliance, US

  STUDY CHAIR

• Kim Chi, MD

  Vancouver Prostate Centre, BC Cancer Agency, Canada

  STUDY CHAIR

• Johann de Bono, Professor

  Institute of Cancer Research, UK

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2010
• First Posted: August 25, 2010
• Study Start: November 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: June 1, 2014
• Last Updated: October 14, 2016

Record last verified: 2016-10

Locations

KR (7); US (25); DE (19); GB (7); HU (9); ES (16); NL (3); IT (14); BE (4); IL (6); FR (14); CA (16)