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Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer (COMET-2)

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ClinicalTrials.gov Identifier: NCT01522443
Recruitment Status : Terminated (Stopped after the outcome of cabozantinib Phase 3 CRPC study XL184-307.)
First Posted : January 31, 2012
Results First Posted : May 23, 2018
Last Update Posted : May 23, 2018
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Prostate Cancer
Castration Resistant Prostate Cancer
Pain
Prostatic Neoplasms
Interventions: Drug: cabozantinib
Drug: mitoxantrone
Drug: prednisone

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient enrolled: 15 March 2012, Data cut off date: 06 October 2014. The study was terminated by the Sponsor after 119 subjects were enrolled which was less than the planned sample size of 246 subjects.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Cabozantinib

Subjects randomized to the cabozantinib arm will also receive placebo mitoxantrone injections (color-matched with methylene blue) and placebo prednisone capsules.

Cabozantinib (XL184) 60 mg tablets taken orally once daily and mitoxantrone-matched placebo infusion every 3 weeks (maximum of 10 infusions) plus prednisone-matched placebo capsules orally twice daily.

Mitoxantrone/Prednisone

Subjects randomized to the mitoxantrone + prednisone arm will also receive placebo cabozantinib tablets.

Mitoxantrone (12mg/m^2) given by IV once every 3 weeks (maximum of 10 infusions) plus prednisone-matched placebo capsules orally twice daily.


Participant Flow:   Overall Study
    Cabozantinib   Mitoxantrone/Prednisone
STARTED [1]   61   58 
COMPLETED [2]   8   3 
NOT COMPLETED   53   55 
No longer receiving clinical benefit                36                28 
Adverse Event                10                15 
Withdrawal by Subject                5                8 
No study treatment given                1                1 
Other                1                3 
[1] Randomized
[2] Subjects still on study treatment at data cut-off date



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cabozantinib

Subjects randomized to the cabozantinib arm will also receive placebo mitoxantrone injections (color-matched with methylene blue) and placebo prednisone capsules.

Cabozantinib (XL184) 60 mg tablets taken orally once daily and mitoxantrone-matched placebo infusion every 3 weeks (maximum of 10 infusions) plus prednisone-matched placebo capsules orally twice daily.

Mitoxantrone/Prednisone

Subjects randomized to the mitoxantrone + prednisone arm will also receive placebo cabozantinib tablets.

Mitoxantrone (12mg/m^2) given by IV once every 3 weeks (maximum of 10 infusions) plus prednisone-matched placebo capsules orally twice daily.

Total Total of all reporting groups

Baseline Measures
   Cabozantinib   Mitoxantrone/Prednisone   Total 
Overall Participants Analyzed 
[Units: Participants]
 61   58   119 
Age, Customized 
[Units: Participants]
     
<65 years   24   26   50 
65 to <75 years   30   26   56 
75 to <85 years   7   6   13 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      0   0.0%      0   0.0%      0   0.0% 
Male      61 100.0%      58 100.0%      119 100.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      2   3.3%      0   0.0%      2   1.7% 
Not Hispanic or Latino      57  93.4%      57  98.3%      114  95.8% 
Unknown or Not Reported      2   3.3%      1   1.7%      3   2.5% 
Race/Ethnicity, Customized 
[Units: Participants]
     
American Indian/Alaska Native   1   0   1 
Asian   1   3   4 
Black/African-American   8   3   11 
Multiple   1   0   1 
White   49   51   100 
Not Reported   0   1   1 
Other   1   0   1 
Geographic Region 
[Units: Participants]
     
North America   44   36   80 
Europe   8   13   21 
Asia   9   9   18 
ECOG Performance Status (per IVRS/IWRS) 
[Units: Participants]
     
0-1 (normal to symptoms, but ambulatory)   53   52   105 
≥2 (ambulatory to incapable of self-care/death)   8   6   14 
Randomization Stratification Factors (per IVRS/IWRS) 
[Units: Participants]
     
ECOG = 0-1 and prior cabazitaxel: yes   18   18   36 
ECOG = 0-1 and prior cabazitaxel: no   35   34   69 
ECOG ≥ 2 and prior cabazitaxel: yes   7   6   13 
ECOG ≥ 2 and prior cabazitaxel: no   1   0   1 
Time from initial diagnosis to randomization 
[Units: Years]
Median (Full Range)
 4.7 
 (0 to 18) 
 5.3 
 (0 to 16) 
 5.0 
 (0 to 18) 
Gleason score at diagnosis (Primary + Secondary) [1] 
[Units: Participants]
     
<7   2   4   6 
 17   21   38 
>7   40   28   68 
Unknown   2   4   6 
Missing   0   1   1 
[1] The Gleason score is used to define prostate cancer prognosis by histologic grading with scores ranging from 2 to 10. A higher Gleason score indicates a more aggressive form of prostate cancer with a worse prognosis.
Prior prostate surgery/procedure [1] 
[Units: Participants]
     
Transurethral resection of the prostate (TURP)   8   6   14 
Radical prostatectomy - with   17   13   30 
Radical prostatectomy - without   3   2   5 
Cyrosurgery   0   1   1 
Bilateral orchiectomy   4   2   6 
Other   55   52   107 
[1] Baseline radical prostatectomy with and without retropubic with pelvic lymphadenectomy measures are provided.
Bone-scan lesion area (BSLA) 
[Units: Mm^2]
Median (Full Range)
 72865.0 
 (0 to 251469) 
 72702.5 
 (679 to 281936) 
 72865.0 
 (0 to 281936) 
Sites of prostate cancer metastasis 
[Units: Participants]
     
Bone   61   58   119 
Lymph node   29   18   47 
Visceral (soft tissue; liver)   8   8   16 
Visceral (soft tissue; lung)   2   5   7 
Other soft tissue   7   3   10 
Pain score (BPI Item 3) during Run-In Stage [1] 
[Units: Units on a scale]
Median (Full Range)
 6.00 
 (4.0 to 8.0) 
 6.14 
 (4.0 to 8.0) 
 6.00 
 (4.0 to 8.0) 
[1] During the Run-In State, subjects will self-report pain by phone via an interactive voice response system (IVRS) daily for 7 days and record analgesic medication information on a paper pain medication diary. Each day of the reporting periods, subjects will report their worst pain intensity and their average pain intensity over a 24-hour period using an 11-point numerical rating system (NRS) (ranging from 0 to 10, with 0 representing “No Pain,” and 10 representing “Pain as Bad as You Can Imagine”).
Pain score (BPI Item 3) during Run-In Stage [1] 
[Units: Participants]
     
4-5   10   15   25 
>5-6   22   13   35 
>6-7   18   15   33 
>7-8   11   15   26 
[1] During the Run-In State, subjects will self-report pain by phone via an interactive voice response system (IVRS) daily for 7 days and record analgesic medication information on a paper pain medication diary. Each day of the reporting periods, subjects will report their worst pain intensity and their average pain intensity over a 24-hour period using an 11-point numerical rating system (NRS) (ranging from 0 to 10, with 0 representing “No Pain,” and 10 representing “Pain as Bad as You Can Imagine”).
Number of prior anticancer agents 
[Units: Participants]
Count of Participants
     
 0   3   3 
 6   4   10 
 20   14   34 
≥5   35   37   72 
Prior cabazitaxel (per IVRS/IWRS) 
[Units: Participants]
Count of Participants
     
Yes      25  41.0%      24  41.4%      49  41.2% 
No      36  59.0%      34  58.6%      70  58.8% 


  Outcome Measures

1.  Primary:   Pain Response at Week 6 Confirmed at Week 12, Week 12 Reported   [ Time Frame: Pain response was measured at Week 6 and Week 12 by self-reports of subjects ]

2.  Secondary:   Bone Scan Response (BSR)   [ Time Frame: BSR was measured at the end of Week 12 as determined by the IRF ]

3.  Secondary:   Overall Survival (OS)   [ Time Frame: OS was measured at the time of randomization until 78 deaths ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Enrollment was stopped before planned study population size of 246 was reached (only 119 enrolled).


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Exelixis Medical Information
Organization: Exelixis, Inc.
phone: 855-292-3935
e-mail: druginfo@exelixis.com



Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT01522443     History of Changes
Other Study ID Numbers: XL184-306
First Submitted: January 13, 2012
First Posted: January 31, 2012
Results First Submitted: May 23, 2017
Results First Posted: May 23, 2018
Last Update Posted: May 23, 2018