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

October 11, 2016 updated by: Achieve Life Sciences

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

630

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
3.4 years
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.
2.7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From randomization to Day 125 to Day 155

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Achieve Life Sciences

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

April 9, 2012

First Submitted That Met QC Criteria

April 16, 2012

First Posted (Estimate)

April 17, 2012

Study Record Updates

Last Update Posted (Estimate)

October 12, 2016

Last Update Submitted That Met QC Criteria

October 11, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OGX-011-12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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