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

NCT ID: NCT01188187

Last Updated: 2016-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1022 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2014-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Custirsen

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Dexamethasone

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Dexamethasone

Intervention Type: 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.

Interventions

Custirsen

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Prednisone

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

OGX-011

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.

• 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.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: collaborator

Achieve Life Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Celestia Higano, MD

Role: STUDY_CHAIR

Seattle Cancer Care Alliance, US

Kim Chi, MD

Role: STUDY_CHAIR

Vancouver Prostate Centre, BC Cancer Agency, Canada

Johann de Bono, Professor

Role: STUDY_CHAIR

Institute of Cancer Research, UK

Locations

Teva Investigational Site 100

Birmingham, Alabama, 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 097

San Diego, California, United States

Teva Investigational Site 090

Fort Collins, Colorado, United States

Teva Investigational Site 106

Fort Myers, Florida, United States

Teva Investigational Site 094

Port Saint Lucie, Florida, United States

Teva Investigational Site 096

Atlanta, Georgia, United States

Teva Investigational Site 103

Baton Rough, Louisiana, United States

Teva Investigational Site 098

Ann Arbor, Michigan, United States

Teva Investigational Site 112

Detroit, Michigan, United States

Teva Investigational Site 032

Rochester, Minnesota, United States

Teva Investigational Site 204

Las Vegas, Nevada, United States

Teva Investigational Site 107

Cincinnati, Ohio, United States

Teva Investigational Site 266

Greensboro, South Carolina, United States

Teva Investigational Site 102

Myrtle Beach, South Carolina, United States

Teva Investigational Site 084

Memphis, Tennessee, United States

Teva Investigational Site 101

Nashville, Tennessee, United States

Teva Investigational Site 116

San Antonio, Texas, United States

Teva Investigational Site 059

Tyler, Texas, United States

Teva Investigational Site 063

Tyler, Texas, United States

Teva Investigational Site 047

Newport, Virginia, United States

Teva Investigational Site 104

Norfolk, Virginia, United States

Teva Investigational Site 029

Seattle, Washington, United States

Teva Investigational Site 862

Bonheiden, , Belgium

Teva Investigational Site 860

Brussels, , Belgium

Teva Investigational Site 864

Edegem, , Belgium

Teva Investigational Site 863

Ghent, , Belgium

Teva Investigational Site 002

Calgary, Alberta, Canada

Teva Investigational Site 023

Edmonton, Alberta, Canada

Teva Investigational Site 118

Abbotsford, British Columbia, Canada

Teva Investigational Site 007

Surrey, British Columbia, Canada

Teva Investigational Site 001

Vancouver, British Columbia, Canada

Teva Investigational Site 085

Victoria, British Columbia, Canada

Teva Investigational Site 024

Winnipeg, Manitoba, 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 091

Oshawa, Ontario, Canada

Teva Investigational Site 003

Ottawa, Ontario, Canada

Teva Investigational Site 004

Toronto, Ontario, Canada

Teva Investigational Site 087

Toronto, Ontario, Canada

Teva Investigational Site 026

Montreal, Quebec, Canada

Teva Investigational Site 027

Montreal, Quebec, Canada

Teva Investigational Site 551

Angers, , France

Teva Investigational Site 552

Avignon, , France

Teva Investigational Site 553

Grenoble, , France

Teva Investigational Site 555

La Roche-sur-Yon, , France

Teva Investigational Site 557

Marseille, , France

Teva Investigational Site 558

Nice, , France

Teva Investigational Site 559

Paris, , France

Teva Investigational Site 560

Paris, , France

Teva Investigational Site 566

Saint-Brieuc, , France

Teva Investigational Site 561

Saint-Herblain, , France

Teva Investigational Site 562

Saint-Priest-en-Jarez, , France

Teva Investigational Site 563

Toulouse, , France

Teva Investigational Site 564

Vandœuvre-lès-Nancy, , France

Teva Investigational Site 550

Villejuif, , France

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

Hanover, , 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

München, , Germany

Teva Investigational Site 601

Münster, , Germany

Teva Investigational Site 602

Nürtingen, , Germany

Teva Investigational Site 603

Stuttgart, , Germany

Teva Investigational Site 610

Tübingen, , Germany

Teva Investigational Site 605

Wuppertal, , Germany

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

Győr, , Hungary

Teva Investigational Site 698

Miskolc, , Hungary

Teva Investigational Site 699

Nyíregyháza, , Hungary

Teva Investigational Site 693

Szeged, , Hungary

Teva Investigational Site 695

Veszprém, , Hungary

Teva Investigational Site 506

Jerusalem, IL, Israel

Teva Investigational Site 507

Haifa, , Israel

Teva Investigational Site 505

Petah Tikva, , Israel

Teva Investigational Site 502

Ramat Gan, , Israel

Teva Investigational Site 503

Tel Aviv, , Israel

Teva Investigational Site 501

Zrifin, , Israel

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

Milan, , 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, , Italy

Teva Investigational Site 851

Amsterdam, , Netherlands

Teva Investigational Site 852

Rotterdam, , Netherlands

Teva Investigational Site 853

Sittard-Geleen, , Netherlands

Teva Investigational Site 404

Cheongju,Chungbuk, , South Korea

Teva Investigational Site 401

Goyang-si Gyeonggi-do, , South Korea

Teva Investigational Site 400

Seoul, , South Korea

Teva Investigational Site 402

Seoul, , South Korea

Teva Investigational Site 403

Seoul, , South Korea

Teva Investigational Site 406

Seoul, , South Korea

Teva Investigational Site 405

Yangsan, , South Korea

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, , Spain

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 710

Metropolitan Borough of Wirral, , United Kingdom

Teva Investigational Site 700

Surrey, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Hungary; Israel; Italy; Netherlands; South Korea; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28283282 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24722180 (View on PubMed)

Other Identifiers

OGX-011-11 TRANSFERRED

Identifier Type: -

Identifier Source: org_study_id