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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01578655
Recruitment Status : Completed
First Posted : April 17, 2012
Last Update Posted : October 12, 2016
Information provided by (Responsible Party):
Achieve Life Sciences

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: cabazitaxel Drug: prednisone Drug: custirsen sodium Phase 3

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 630 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 3 Study Comparing Cabazitaxel/Prednisone in Combination With Custirsen (OGX-011) to Cabazitaxel/Prednisone for Second-Line Chemotherapy in Men With Metastatic Castrate Resistant Prostate Cancer (AFFINITY)
Study Start Date : August 2012
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Cabazitaxel plus Custirsen
cabazitaxel, prednisone, and custirsen sodium
Drug: 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

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

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
Other Names:
  • OGX-011
  • TV-1011

Active Comparator: Cabazitaxel
cabazitaxel and prednisone
Drug: 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

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

Primary Outcome Measures :
  1. Survival in the intent-to-treat population [ Time Frame: 3.4 years ]
    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).

  2. Survival in the poor-prognosis patient population [ Time Frame: 2.7 years ]
    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.

Secondary Outcome Measures :
  1. Progression-free survival at Day 140 [ Time Frame: From randomization to Day 125 to Day 155 ]
    To compare the arms with respect to the proportion of patients having a milestone Day 140 status of Alive Without Event (within the window of Day 125-155 post-randomization). An event is defined as disease progression or death on or before Day 140.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01578655

  Hide Study Locations
United States, California
Prostate Oncology Specialists
Marina Del Rey, California, United States
University of California Davis Medical Center
Sacramento, California, United States
Sharp Health Care
San Diego, California, United States
California Pacific Medical Center Research Institute
San Francisco, California, United States
United States, Colorado
Rocky Mountain Cancer Center
Boulder, Colorado, United States
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States
Smilow Cancer Hospital at Yale New Haven Hospital
New Haven, Connecticut, United States
United States, Florida
The Center for Hematology-Oncology
Boca Raton, Florida, United States
Florida Cancer Specialists
Fort Myers, Florida, United States
Florida Cancer Specialists
Inverness, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
United States, Georgia
Georgia Cancer Specialists, P.C.
Marietta, Georgia, United States
United States, Kansas
Cancer Center of Kansas
Wichita, Kansas, United States
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States
United States, Nebraska
Urology Cancer Center and GU Research Network
Omaha, Nebraska, United States
United States, New York
Albert Einstein Medical Center
Bronx, New York, United States
Monter Cancer Center
Lake Success, New York, United States
SUNY Upstate Medical University
Syracuse, New York, United States
United States, North Carolina
Blumenthal Cancer Center
Charlotte, North Carolina, United States
Cancer Centers of North Carolina
Raleigh, North Carolina, United States
United States, Ohio
Oncology Hematology Care, Inc.
Blue Ash, Ohio, United States
The Mark H. Zangmeister Center
Columbus, Ohio, United States
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States
Cancer Centers of the Carolinas
Greenville, South Carolina, United States
United States, Tennessee
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, United States
The West Clinic
Memphis, Tennessee, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
United States, Texas
Texas Oncology, PA
Dallas, Texas, United States
United States, Utah
Utah Cancer Specialists
Salt Lake City, Utah, United States
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States
Virginia Cancer Institute
Richmond, Virginia, United States
Australia, Australian Capital Territory
The Canberra Hospital
Garran, Australian Capital Territory, Australia
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
St George Public Hospital
Kogarah, New South Wales, Australia
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Australia, Queensland
Haematology and Oncology Clinics of Australia
Brisbane, Queensland, Australia
Australia, South Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Epworth Healthcare
Richmond, Victoria, Australia
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada
Canada, Ontario
Juravinski Cancer Centre
Hamilton, Ontario, Canada
London Health Sciences Center
London, Ontario, Canada
R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa
Oshawa, Ontario, Canada
The Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Canada, Quebec
CHUM-Hospital Notre-Dame
Montréal, Quebec, Canada
Czech Republic
Krajská nemo. T.Bati, a. s.
Zlín, Severomoravsky Kraj, Czech Republic
Fakultni nemo Hradec Králové
Hradec Králové, Czech Republic
Krajská nemocnice Liberec a.s.
Liberec, Czech Republic
University Hospital Olomouc
Olomouc, Czech Republic
Centre François Baclesse
Caen cedex 05, Basse-Normandie, France
Institut Jean-Godinot
Reims, Champagne-Ardenne, France
Hôpital Saint Louis
Paris, Ile de France, France
Institut Curie
Paris Cedex 05, Ile-de-France, France
Institut Gustave Roussy
Villejuif, Ile-de-France, France
Institut de Cancérologie de l'Ouest - René Gauducheau
Saint Herblain, Pays de la Loire, France
Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie
Poitiers Cedex, Poitou-Charentes, France
Centre Antoine Lacassagne
Nice Cedex 2, Provence Alpes Cote d'Azur, France
Centre Léon Bérard
Lyon cédex 08, Rhone-Alpes, France
Institut Paoli Calmettes
Marseille, France
Pándy Kálmán Megyei Kórház
Gyula, Bekes, Hungary
Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház
Miskolc, Borsod-Abauj-Zemplen, Hungary
Szegedi Tudományegyetem, Onkoterápiás Klinika
Szeged, Csongrad, Hungary
Országos Onkológiai Intézet
Budapest, Hungary
Semmelweis Egyetem Általános Orvostudományi Kar
Budapest, Hungary
Russian Federation
Sverdlovsk Reg Clin Hosp#1
Ekaterinburg, Ural, Russian Federation
Volgograd Regional Oncological Dispensary
Volzhskiy, Volgograd, Russian Federation
S Inst Hlth Altay Reg Onc Disp
Barnaul, Russian Federation
Ivanovo Reg Oncology Centre
Ivanovo, Russian Federation
Cancer Research Center na NN Blokhin
Moscow, Russian Federation
Hertzen Rsrch Inst of Oncology
Moscow, Russian Federation
Russian Research Center of Radiology
Moscow, Russian Federation
Urology Research Institute
Moscow, Russian Federation
State Healthcare Inst Omsk Reg
Omsk, Russian Federation
Petrov Research Oncology Institute
Saint Petersburg, Russian Federation
Saint Petersburg City Oncological Dispensary
Saint Petersburg, Russian Federation
Stavropol Reg Oncology Ctr
Stavropol, Russian Federation
United Kingdom
Cancer Research UK
Birmingham, England, United Kingdom
Addenbrookes Hospital Cambridge
Cambridge, England, United Kingdom
U of Surrey Post Grad Med
Guildford, England, United Kingdom
Christie Hospital NHS Foundation Trust
Manchester, England, United Kingdom
Nottingham City Hospital NHS Trust
Nottingham, England, United Kingdom
The Royal Marsden Hospital
Surrey, England, United Kingdom
Musgrove Park Hospital
Taunton, England, United Kingdom
Clatterbridge Centre for Oncology NHS Foundation Trust
Wirral, England, United Kingdom
Beatson Cancer Centre, Glasgow
Glasgow, Scotland, United Kingdom
Sponsors and Collaborators
Achieve Life Sciences
Principal Investigator: 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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Achieve Life Sciences Identifier: NCT01578655     History of Changes
Other Study ID Numbers: OGX-011-12
First Posted: April 17, 2012    Key Record Dates
Last Update Posted: October 12, 2016
Last Verified: October 2016

Keywords provided by Achieve Life Sciences:
custirsen sodium
prostate cancer
metastatic castrate resistant prostate cancer
overall survival

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents