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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by OncoGenex Technologies
Sponsor:
Collaborator:
Teva Pharmaceutical Industries
Information provided by (Responsible Party):
OncoGenex Technologies
ClinicalTrials.gov Identifier:
NCT01578655
First received: April 9, 2012
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Prostate Cancer
Drug: cabazitaxel, prednisone, custirsen sodium
Drug: cabazitaxel, prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by OncoGenex Technologies:

Primary Outcome Measures:
  • Survival [ Time Frame: 3.4 years ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Progression-free survival at Day 140 [ Time Frame: From randomization to Day 125 to Day 155 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 630
Study Start Date: August 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cabazitaxel, prednisone, custirsen Drug: cabazitaxel, prednisone, custirsen sodium
Following 3 loading doses of custirsen (640 mg IV), cabazitaxel (25mg/m² IV) is administered on a 3-week cycle with weekly custirsen (640 mg IV) and daily prednisone (10 mg PO) until disease progression, unacceptable toxicity, or completion of 10 cycles
Other Name: OGX-011, TV-1011
Active Comparator: cabazitaxel and prednisone Drug: cabazitaxel, prednisone
Cabazitaxel (25 mg/m² IV) is administered on a 3-week cycle with daily prednisone (10 mg PO) until disease progression, unacceptable toxicity, or completion of 10 cycles

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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01578655

Contacts
Contact: Daniel Cain 425-686-1546 dcain@oncogenex.com

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

Publications:
Responsible Party: OncoGenex Technologies
ClinicalTrials.gov Identifier: NCT01578655     History of Changes
Other Study ID Numbers: OGX-011-12
Study First Received: April 9, 2012
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by OncoGenex Technologies:
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
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014