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

NCT01578655 | Completed Phase 3 DMC

• 1 other identifier: OGX-011-12
• Study Type: interventional
• Target: 630
• Locations: 8 countries
• Sites: 94

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

custirsen sodium; prostate cancer; metastatic castrate resistant prostate cancer; overall survival

Outcome Measures

Primary Outcomes (2)

• Survival in the intent-to-treat population

  To determine whether the survival for patients randomized to the investigational arm (cabazitaxel/prednisone plus custirsen) is consistent with longer survival as compared to patients randomized to the control arm (cabazitaxel/prednisone).

  3.4 years

• Survival in the poor-prognosis patient population

  To determine whether the survival for patients randomized to the investigational arm (cabazitaxel/prednisone plus custirsen) and identified as having poor prognosis is consistent with longer survival as compared to patients randomized to the control arm (cabazitaxel/prednisone) and identified as having poor prognosis.

  2.7 years

Secondary Outcomes (1)

• Progression-free survival at Day 140

  From randomization to Day 125 to Day 155

Study Arms (2)

Cabazitaxel plus Custirsen

EXPERIMENTAL

cabazitaxel, prednisone, and custirsen sodium

Drug: cabazitaxel; Drug: prednisone; Drug: custirsen sodium

Cabazitaxel

ACTIVE COMPARATOR

cabazitaxel and prednisone

Drug: cabazitaxel; Drug: prednisone

Interventions

cabazitaxel 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

Cabazitaxel; Cabazitaxel plus Custirsen

prednisone DRUG

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

Cabazitaxel; Cabazitaxel plus Custirsen

custirsen sodium 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

Also known as: OGX-011, TV-1011

Cabazitaxel plus Custirsen

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (94)

Prostate Oncology Specialists

Marina del Rey, California, United States

Location

University of California Davis Medical Center

Sacramento, California, United States

Location

Sharp Health Care

San Diego, California, United States

Location

California Pacific Medical Center Research Institute

San Francisco, California, United States

Location

Rocky Mountain Cancer Center

Boulder, Colorado, United States

Location

Hartford Hospital

Hartford, Connecticut, United States

Location

Smilow Cancer Hospital at Yale New Haven Hospital

New Haven, Connecticut, United States

Location

The Center for Hematology-Oncology

Boca Raton, Florida, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, United States

Location

Florida Cancer Specialists

Inverness, Florida, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Location

Georgia Cancer Specialists, P.C.

Marietta, Georgia, United States

Location

Cancer Center of Kansas

Wichita, Kansas, United States

Location

Boston University Medical Center

Boston, Massachusetts, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

Urology Cancer Center and GU Research Network

Omaha, Nebraska, United States

Location

Monter Cancer Center

Lake Success, New York, United States

Location

SUNY Upstate Medical University

Syracuse, New York, United States

Location

Albert Einstein Medical Center

The Bronx, New York, United States

Location

Blumenthal Cancer Center

Charlotte, North Carolina, United States

Location

Cancer Centers of North Carolina

Raleigh, North Carolina, United States

Location

Oncology Hematology Care, Inc.

Blue Ash, Ohio, United States

Location

The Mark H. Zangmeister Center

Columbus, Ohio, United States

Location

Oregon Health and Science University

Portland, Oregon, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, United States

Location

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Location

Chattanooga Oncology and Hematology Associates

Chattanooga, Tennessee, United States

Location

The West Clinic

Memphis, Tennessee, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Location

Texas Oncology, PA

Dallas, Texas, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, United States

Location

Virginia Cancer Institute

Richmond, Virginia, United States

Location

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Location

St George Public Hospital

Kogarah, New South Wales, Australia

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Location

Westmead Hospital

Westmead, New South Wales, Australia

Location

Haematology and Oncology Clinics of Australia

Brisbane, Queensland, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, Australia

Location

Box Hill Hospital

Box Hill, Victoria, Australia

Location

Austin Health

Heidelberg, Victoria, Australia

Location

Epworth Healthcare

Richmond, Victoria, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

London Health Sciences Center

London, Ontario, Canada

Location

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

Oshawa, Ontario, Canada

Location

The Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

CHUM-Hospital Notre-Dame

Montreal, Quebec, Canada

Location

Krajská nemocnice Liberec a.s.

Liberec, Liberec, Czechia

Location

Krajská nemo. T.Bati, a. s.

Zlín, Severomoravsky Kraj, Czechia

Location

Fakultni nemo Hradec Králové

Hradec Králové, Czechia

Location

University Hospital Olomouc

Olomouc, Czechia

Location

Centre Léon Bérard

Lyon Cédex 08, Auvergne-Rhône-Alpes, France

Location

Centre François Baclesse

Caen, Basse-Normandie, France

Location

Institut Jean-Godinot

Reims, Champagne-Ardenne, France

Location

Institut Paoli Calmettes

Marseille, Marseille, France

Location

Institut de Cancérologie de l'Ouest - René Gauducheau

Saint-Herblain, Pays de la Loire Region, France

Location

Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie

Poitiers, Poitou-Charentes, France

Location

Centre Antoine Lacassagne

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

Location

Hôpital Saint Louis

Paris, Île-de-France Region, France

Location

Institut Curie

Paris, Île-de-France Region, France

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Location

Pándy Kálmán Megyei Kórház

Gyula, Bekes County, Hungary

Location

Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház

Miskolc, Borsod-Abauj Zemplen county, Hungary

Location

Országos Onkológiai Intézet

Budapest, Budapest, Hungary

Location

Semmelweis Egyetem Általános Orvostudományi Kar

Budapest, Budapest, Hungary

Location

Szegedi Tudományegyetem, Onkoterápiás Klinika

Szeged, Csongrád megye, Hungary

Location

Ivanovo Reg Oncology Centre

Ivanovo, Ivanovo Oblast, Russia

Location

Cancer Research Center na NN Blokhin

Moscow, Moscow, Russia

Location

Hertzen Rsrch Inst of Oncology

Moscow, Moscow, Russia

Location

Sverdlovsk Reg Clin Hosp#1

Yekaterinburg, Ural, Russia

Location

Volgograd Regional Oncological Dispensary

Volzhsky, Volgograd Oblast, Russia

Location

S Inst Hlth Altay Reg Onc Disp

Barnaul, Russia

Location

Russian Research Center of Radiology

Moscow, Russia

Location

Urology Research Institute

Moscow, Russia

Location

State Healthcare Inst Omsk Reg

Omsk, Russia

Location

Petrov Research Oncology Institute

Saint Petersburg, Russia

Location

Saint Petersburg City Oncological Dispensary

Saint Petersburg, Russia

Location

Stavropol Reg Oncology Ctr

Stavropol, Russia

Location

Cancer Research UK

Birmingham, England, United Kingdom

Location

Addenbrookes Hospital Cambridge

Cambridge, England, United Kingdom

Location

U of Surrey Post Grad Med

Guildford, England, United Kingdom

Location

Christie Hospital NHS Foundation Trust

Manchester, England, United Kingdom

Location

Clatterbridge Centre for Oncology NHS Foundation Trust

Metropolitan Borough of Wirral, England, United Kingdom

Location

Nottingham City Hospital NHS Trust

Nottingham, England, United Kingdom

Location

The Royal Marsden Hospital

Surrey, England, United Kingdom

Location

Musgrove Park Hospital

Taunton, England, United Kingdom

Location

Beatson Cancer Centre, Glasgow

Glasgow, Scotland, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 21788353 BACKGROUND

• 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.

  PMID: 20733135 BACKGROUND

• 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.

  PMID: 29033099 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; Prednisone; OGX-011

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)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Thomasz Beer, MD

  Oregon Health & Science University, Portland, Oregon

  PRINCIPAL INVESTIGATOR

• Karim Fazazi, MD

  Gustave Roussy Cancer Institute, University of Paris, France

  PRINCIPAL INVESTIGATOR

• Sebastien Hotte, MD

  Juravinski Cancer Centre, Hamilton, Ontario, Canada

  PRINCIPAL INVESTIGATOR

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: April 9, 2012
• First Posted: April 17, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: October 12, 2016

Record last verified: 2016-10

Locations

CA (8); GB (9); HU (5); US (35); CZ (4); FR (10); RU (12); AU (11)