Comparison of Cabazitaxel/Prednisone Alone or in Combination With Custirsen for 2nd Line Chemotherapy in Prostate Cancer

NCT ID: NCT01578655

Last Updated: 2016-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

630 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2016-07-31

Brief Summary

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This Phase 3 study has been designed to confirm that adding custirsen to cabazitaxel/prednisone treatment can slow tumor progression and enhance survival outcomes compared to standard cabazitaxel/prednisone treatment in men with metastatic castrate resistant prostate cancer (CRPC). This will be a randomized, open-label, multicenter, international trial. Treatment will consist of cabazitaxel/prednisone/custirsen vs. cabazitaxel/prednisone. A total of approximately 630 patients will be randomized with equal probability to the two arms.

Detailed Description

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Until recently, options for second-line chemotherapy in CRPC have included docetaxel retreatment, mitoxantrone, or other chemotherapies, without proven clinical benefit. In 2010, a Phase 3 second-line chemotherapy trial (TROPIC) showed a survival advantage for cabazitaxel, a semi-synthetic taxane selected to overcome the emergence of taxane resistance, when compared to mitoxantrone.

Clusterin is a stress-activated cytoprotective chaperone up-regulated by a variety of anti-cancer therapies that confers treatment resistance when over-expressed. Inhibition of clusterin expression using custirsen has been shown to enhance tumor cell death following treatment with chemotherapy.

The clinical activity of custirsen in combination with the taxane docetaxel has been shown in two Phase 2 studies. Given the results observed using a taxane as either first-line or second-line chemotherapy in CRPC, combination with custirsen may decrease taxane resistance and enhance the survival benefit of taxane therapy. Thus, a combination of custirsen with cabazitaxel may further enhance survival in second-line taxane chemotherapy for CRPC.

Conditions

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Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cabazitaxel plus Custirsen

cabazitaxel, prednisone, and custirsen sodium

Group Type EXPERIMENTAL

cabazitaxel

Intervention Type DRUG

Cabazitaxel (25mg/m² IV) is administered on day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles

prednisone

Intervention Type DRUG

Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles

custirsen sodium

Intervention Type DRUG

Custirsen is administered as 3 loading doses (640 mg IV each) within 9 days, followed by weekly custirsen (640 mg IV) during each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles

Cabazitaxel

cabazitaxel and prednisone

Group Type ACTIVE_COMPARATOR

cabazitaxel

Intervention Type DRUG

Cabazitaxel (25mg/m² IV) is administered on day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles

prednisone

Intervention Type DRUG

Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles

Interventions

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cabazitaxel

Cabazitaxel (25mg/m² IV) is administered on day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles

Intervention Type DRUG

prednisone

Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles

Intervention Type DRUG

custirsen sodium

Custirsen is administered as 3 loading doses (640 mg IV each) within 9 days, followed by weekly custirsen (640 mg IV) during each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles

Intervention Type DRUG

Other Intervention Names

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OGX-011 TV-1011

Eligibility Criteria

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Inclusion Criteria

* Histological or cytological diagnosis of adenocarcinoma of the prostate
* Metastatic disease on chest, abdominal, or pelvic CT scan and/or bone scan
* Previous first-line treatment for CRPC with a docetaxel-containing regimen
* Current progressive disease
* Increasing serum PSA level (for patients who progress based only on increasing serum PSA level, a minimum starting value of 5.0 ng/mL is required)
* Baseline laboratory values as defined
* Willing to continue primary androgen suppression with gonadotropin-releasing hormone (GnRH) analogues (unless treated with bilateral orchiectomy)
* Karnofsky score ≥70%
* At least 21 days have passed since completing radiotherapy
* At least 21 days have passed since receiving any investigational agent at the time of randomization
* At least 21 days have passed since major surgery
* Recovered from any docetaxel therapy-related neuropathy to ≤grade 1 at the time of randomization
* Recovered from all therapy related toxicity to ≤grade 2 (except alopecia, anemia, and any signs or symptoms of androgen deprivation therapy) at the time of randomization
* Able to tolerate a starting dose of 25 mg/m² cabazitaxel
* Willing to not add, delete, or change current bisphosphonate or denosumab usage
* Able to tolerate oral prednisone at 10 mg per day
* Competent to provide written informed consent

Exclusion Criteria

* Received any other cytotoxic chemotherapy beyond the first-line docetaxel-containing regimen as treatment for prostate cancer
* Received prior radioisotope with strontium 89 or samarium 153
* Received any cycling, intermittent, or continuous hormonal treatment within 21 days prior to randomization with the exception of the continuous GnRH analogues (prior treatment with abiraterone or MDV3100 is allowed as long as 21 days have passed since last dose)
* Participated in a prior Phase 3 clinical study evaluating custirsen regardless of study arm assignment
* Requiring ongoing treatment during the study with medications known to be either strong CYP3A inhibitors or strong CYP3A inducers
* History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated
* Current symptomatic cord compression requiring surgery or radiation therapy
* Active second malignancy (except non melanomatous skin or superficial bladder cancer) defined in general as requiring anticancer therapy or at high risk of recurrence during the study
* Uncontrolled medical condition or significant concurrent illness that in the opinion of the Investigator would preclude protocol therapy
* Known severe hypersensitivity to taxanes or polysorbate 80-containing drugs
* Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Achieve Life Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomasz Beer, MD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health & Science University, Portland, Oregon

Karim Fazazi, MD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy Cancer Institute, University of Paris, France

Sebastien Hotte, MD

Role: PRINCIPAL_INVESTIGATOR

Juravinski Cancer Centre, Hamilton, Ontario, Canada

Locations

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Prostate Oncology Specialists

Marina del Rey, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

Sharp Health Care

San Diego, California, United States

Site Status

California Pacific Medical Center Research Institute

San Francisco, California, United States

Site Status

Rocky Mountain Cancer Center

Boulder, Colorado, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Smilow Cancer Hospital at Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

The Center for Hematology-Oncology

Boca Raton, Florida, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists

Inverness, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Georgia Cancer Specialists, P.C.

Marietta, Georgia, United States

Site Status

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status

Boston University Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Urology Cancer Center and GU Research Network

Omaha, Nebraska, United States

Site Status

Monter Cancer Center

Lake Success, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Albert Einstein Medical Center

The Bronx, New York, United States

Site Status

Blumenthal Cancer Center

Charlotte, North Carolina, United States

Site Status

Cancer Centers of North Carolina

Raleigh, North Carolina, United States

Site Status

Oncology Hematology Care, Inc.

Blue Ash, Ohio, United States

Site Status

The Mark H. Zangmeister Center

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

South Carolina Oncology Associates

Columbia, South Carolina, United States

Site Status

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Site Status

Chattanooga Oncology and Hematology Associates

Chattanooga, Tennessee, United States

Site Status

The West Clinic

Memphis, Tennessee, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Texas Oncology, PA

Dallas, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Virginia Cancer Institute

Richmond, Virginia, United States

Site Status

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

St George Public Hospital

Kogarah, New South Wales, Australia

Site Status

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Haematology and Oncology Clinics of Australia

Brisbane, Queensland, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Epworth Healthcare

Richmond, Victoria, Australia

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Site Status

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

London Health Sciences Center

London, Ontario, Canada

Site Status

R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Site Status

The Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

CHUM-Hospital Notre-Dame

Montreal, Quebec, Canada

Site Status

Krajská nemocnice Liberec a.s.

Liberec, Liberec, Czechia

Site Status

Krajská nemo. T.Bati, a. s.

Zlín, Severomoravsky Kraj, Czechia

Site Status

Fakultni nemo Hradec Králové

Hradec Králové, , Czechia

Site Status

University Hospital Olomouc

Olomouc, , Czechia

Site Status

Centre Léon Bérard

Lyon Cédex 08, Auvergne-Rhône-Alpes, France

Site Status

Centre François Baclesse

Caen, Basse-Normandie, France

Site Status

Institut Jean-Godinot

Reims, Champagne-Ardenne, France

Site Status

Institut Paoli Calmettes

Marseille, Marseille, France

Site Status

Institut de Cancérologie de l'Ouest - René Gauducheau

Saint-Herblain, Pays de la Loire Region, France

Site Status

Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie

Poitiers, Poitou-Charentes, France

Site Status

Centre Antoine Lacassagne

Nice, Provence-Alpes-Côte d'Azur Region, France

Site Status

Hôpital Saint Louis

Paris, Île-de-France Region, France

Site Status

Institut Curie

Paris, Île-de-France Region, France

Site Status

Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Site Status

Pándy Kálmán Megyei Kórház

Gyula, Bekes County, Hungary

Site Status

Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház

Miskolc, Borsod-Abauj Zemplen county, Hungary

Site Status

Országos Onkológiai Intézet

Budapest, Budapest, Hungary

Site Status

Semmelweis Egyetem Általános Orvostudományi Kar

Budapest, Budapest, Hungary

Site Status

Szegedi Tudományegyetem, Onkoterápiás Klinika

Szeged, Csongrád megye, Hungary

Site Status

Ivanovo Reg Oncology Centre

Ivanovo, Ivanovo Oblast, Russia

Site Status

Cancer Research Center na NN Blokhin

Moscow, Moscow, Russia

Site Status

Hertzen Rsrch Inst of Oncology

Moscow, Moscow, Russia

Site Status

Sverdlovsk Reg Clin Hosp#1

Yekaterinburg, Ural, Russia

Site Status

Volgograd Regional Oncological Dispensary

Volzhsky, Volgograd Oblast, Russia

Site Status

S Inst Hlth Altay Reg Onc Disp

Barnaul, , Russia

Site Status

Russian Research Center of Radiology

Moscow, , Russia

Site Status

Urology Research Institute

Moscow, , Russia

Site Status

State Healthcare Inst Omsk Reg

Omsk, , Russia

Site Status

Petrov Research Oncology Institute

Saint Petersburg, , Russia

Site Status

Saint Petersburg City Oncological Dispensary

Saint Petersburg, , Russia

Site Status

Stavropol Reg Oncology Ctr

Stavropol, , Russia

Site Status

Cancer Research UK

Birmingham, England, United Kingdom

Site Status

Addenbrookes Hospital Cambridge

Cambridge, England, United Kingdom

Site Status

U of Surrey Post Grad Med

Guildford, England, United Kingdom

Site Status

Christie Hospital NHS Foundation Trust

Manchester, England, United Kingdom

Site Status

Clatterbridge Centre for Oncology NHS Foundation Trust

Metropolitan Borough of Wirral, England, United Kingdom

Site Status

Nottingham City Hospital NHS Trust

Nottingham, England, United Kingdom

Site Status

The Royal Marsden Hospital

Surrey, England, United Kingdom

Site Status

Musgrove Park Hospital

Taunton, England, United Kingdom

Site Status

Beatson Cancer Centre, Glasgow

Glasgow, Scotland, United Kingdom

Site Status

Countries

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United States Australia Canada Czechia France Hungary Russia United Kingdom

References

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Saad F, Hotte S, North S, Eigl B, Chi K, Czaykowski P, Wood L, Pollak M, Berry S, Lattouf JB, Mukherjee SD, Gleave M, Winquist E; Canadian Uro-Oncology Group. Randomized phase II trial of Custirsen (OGX-011) in combination with docetaxel or mitoxantrone as second-line therapy in patients with metastatic castrate-resistant prostate cancer progressing after first-line docetaxel: CUOG trial P-06c. Clin Cancer Res. 2011 Sep 1;17(17):5765-73. doi: 10.1158/1078-0432.CCR-11-0859. Epub 2011 Jul 25.

Reference Type BACKGROUND
PMID: 21788353 (View on PubMed)

Chi KN, Hotte SJ, Yu EY, Tu D, Eigl BJ, Tannock I, Saad F, North S, Powers J, Gleave ME, Eisenhauer EA. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Sep 20;28(27):4247-54. doi: 10.1200/JCO.2009.26.8771. Epub 2010 Aug 23.

Reference Type BACKGROUND
PMID: 20733135 (View on PubMed)

Beer TM, Hotte SJ, Saad F, Alekseev B, Matveev V, Flechon A, Gravis G, Joly F, Chi KN, Malik Z, Blumenstein B, Stewart PS, Jacobs CA, Fizazi K. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1532-1542. doi: 10.1016/S1470-2045(17)30605-8. Epub 2017 Oct 9.

Reference Type DERIVED
PMID: 29033099 (View on PubMed)

Other Identifiers

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OGX-011-12

Identifier Type: -

Identifier Source: org_study_id

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