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

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ClinicalTrials.gov Identifier: NCT01578655
Recruitment Status : Completed
First Posted : April 17, 2012
Last Update Posted : October 12, 2016
Sponsor:
Information provided by (Responsible Party):
Achieve Life Sciences

Tracking Information
First Submitted Date  ICMJE April 9, 2012
First Posted Date  ICMJE April 17, 2012
Last Update Posted Date October 12, 2016
Study Start Date  ICMJE August 2012
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 23, 2015)
  • 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).
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2012)		 Survival [ 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2012)		 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison of Cabazitaxel/Prednisone Alone or in Combination With Custirsen for 2nd Line Chemotherapy in Prostate Cancer
Official Title  ICMJE 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)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Cabazitaxel plus Custirsen
    cabazitaxel, prednisone, and custirsen sodium
    Interventions:
    • Drug: cabazitaxel
    • Drug: prednisone
    • Drug: custirsen sodium
  • Active Comparator: Cabazitaxel
    cabazitaxel and prednisone
    Interventions:
    • Drug: cabazitaxel
    • Drug: prednisone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2012)		 630
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Czech Republic,   France,   Hungary,   Russian Federation,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01578655
Other Study ID Numbers  ICMJE OGX-011-12
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Achieve Life Sciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Achieve Life Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Achieve Life Sciences
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP