XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC)

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00417079
First received: December 28, 2006
Last updated: March 4, 2011
Last verified: March 2011
Results First Received: September 20, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Neoplasms
Prostatic Neoplasms
Interventions: Drug: cabazitaxel (XRP6258) (RPR116258)
Drug: mitoxantrone
Drug: prednisone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Multicenter study: 146 actives sites from 26 countries in Europe, USA, South America and Asia Pacific region. Study initiation date: January 2nd, 2007; study completion date/study cut off date: September 25th, 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

165 patients signed informed consent but were not randomized and considered as screen failure.

Intention to Treat Population (ITT or randomized patients): 755 patients (377 mitoxantrone, 378 cabazitaxel).

Safety population (treated patients): 742 patients (371 mitoxantrone, 371 cabazitaxel) (Patients not treated: 6 mitoxantrone, 7 cabazitaxel).


Reporting Groups
  Description
Mitoxantrone + Prednisone mitoxantrone 12 mg/m^2 (Day 1) by intravenous (IV) every 3 weeks, and prednisone 10 mg orally given daily
Cabazitaxel + Prednisone cabazitaxel 25 mg/m^2 (Day 1) by intravenous (IV) every 3 weeks, and prednisone 10 mg orally given daily

Participant Flow:   Overall Study
    Mitoxantrone + Prednisone     Cabazitaxel + Prednisone  
STARTED     377 [1]   378 [1]
COMPLETED     46 [1]   105 [1]
NOT COMPLETED     331     273  
Disease progression                 267                 180  
Adverse Event                 32                 67  
Non-compliance to protocol                 0                 1  
Lost to Follow-up                 2                 0  
Withdrawal by Subject                 17                 8  
Not treated                 6                 7  
Screened failure                 2                 1  
Investigator's decision                 1                 4  
Non-confirmed Disease progression                 1                 1  
Clinical deterioration                 1                 0  
Screening error                 2                 1  
Withdrawal by subject's family                 0                 1  
Patient unable to come to the clinic                 0                 1  
abnormal liver function tests                 0                 1  
[1] Randomized patients



  Baseline Characteristics
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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
Mitoxantrone + Prednisone mitoxantrone 12 mg/m^2 (Day 1) by intravenous (IV) every 3 weeks, and prednisone 10 mg orally given daily
Cabazitaxel + Prednisone cabazitaxel 25 mg/m^2 (Day 1) by intravenous (IV) every 3 weeks, and prednisone 10 mg orally given daily
Total Total of all reporting groups

Baseline Measures
    Mitoxantrone + Prednisone     Cabazitaxel + Prednisone     Total  
Number of Participants  
[units: participants]
  377     378     755  
Age  
[units: years]
Median ( Full Range )
  67.0  
  ( 47 to 89 )  
  68.0  
  ( 46 to 92 )  
  67  
  ( 46 to 92 )  
Gender, Customized  
[units: participants]
     
Male     377     378     755  
Region of Enrollment  
[units: participants]
     
United States     106     97     203  
Taiwan     4     7     11  
Slovakia     1     1     2  
Spain     10     9     19  
Chile     9     12     21  
Russian Federation     6     4     10  
Italy     17     18     35  
India     11     9     20  
France     44     46     90  
Denmark     19     26     45  
South Africa     7     9     16  
Netherlands     8     9     17  
Korea, Republic of     8     7     15  
Finland     4     1     5  
Turkey     17     19     36  
United Kingdom     17     20     37  
Hungary     8     7     15  
Czech Republic     10     12     22  
Mexico     2     3     5  
Canada     16     16     32  
Argentina     7     3     10  
Brazil     7     4     11  
Belgium     16     15     31  
Singapore     6     3     9  
Germany     6     11     17  
Sweden     11     10     21  
Eastern Cooperative Oncology Group (ECOG) Performance Status  
[units: Participants]
     
0 - Fully Active     120     141     261  
1 - Ambulatory, Restricted Activity     224     209     433  
2 - Ambulatory, No Work Activities     33     28     61  
Prostatic Specific Antigen PSA  
[units: ng/mL]
Median ( Full Range )
  127.5  
  ( 2 to 11220 )  
  143.9  
  ( 2 to 7842 )  
  135.00  
  ( 2 to 11220 )  
Measurable disease [1]
[units: Participants]
     
Measurable disease     204     201     405  
Not Measurable disease     173     177     350  
Extent of disease [2]
[units: Participants]
     
Metastatic     356     364     720  
Locoregional Recurrence     20     14     34  
Missing     1     0     1  
Tumor Location: number of sites involved  
[units: Participants]
     
1     134     146     280  
2     117     112     229  
3     78     73     151  
4 or more     43     44     87  
Missing     5     3     8  
[1]

Measurability of the disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria:

Patients with measurable disease have at least one visceral or soft tissue metastatic lesion (including new lesion).

Patient with non-measurable disease have documented rising PSA levels or appearance of new lesion.

[2]

Extent of the disease at screening stage:

  • Metastatic: bone or visceral metastases.
  • Locoregional recurrence includes local recurrent tumor at the primary site, along the draining lymphatic channels, or within the draining lymphatic nodal basin.



  Outcome Measures
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1.  Primary:   Overall Survival   [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ]
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Measure Type Primary
Measure Title Overall Survival
Measure Description

Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause.

In the absence of confirmation of death, the survival time was censored at the last date patient was known to be alive or at the cut-off date, whichever had come first.

Time Frame From the date of randomization up to 104 weeks (study cut-off)  
Safety Issue No  

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.
Analysis was performed on the intention To Treat (ITT) population. The ITT population is composed of all randomized patients (i.e. patients assigned to a treatment group by the randomization, regardless of whether patients received any study drug or received a different study drug from which they were randomized).

Reporting Groups
  Description
Mitoxantrone + Prednisone mitoxantrone 12 mg/m^2 (Day 1) by intravenous (IV) every 3 weeks, and prednisone 10 mg orally given daily
Cabazitaxel + Prednisone cabazitaxel 25 mg/m^2 (Day 1) by intravenous (IV) every 3 weeks, and prednisone 10 mg orally given daily

Measured Values
    Mitoxantrone + Prednisone     Cabazitaxel + Prednisone  
Number of Participants Analyzed  
[units: participants]
  377     378  
Overall Survival  
[units: Months]
Median ( 95% Confidence Interval )
  12.7  
  ( 11.6 to 13.7 )  
  15.1  
  ( 14.1 to 16.3 )  


Statistical Analysis 1 for Overall Survival
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.0001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The study required an estimated sample size of 720 patients (360 per arm) in order to detect a 25% reduction in the hazard ratio for death in the cabazitaxel group relative to the mitoxantrone group with 90% power. The final analysis was planned for when 511 deaths had occurred.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Analysis was performed by using a log-rank comparisons stratified according to disease measurability and ECOG performance status (0-1 versus 2)
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  A 2-sided significance level of 0.0452 was used for the final analysis based on an interim analysis performed after 307 events with an adjusted significance level of 0.016 based on the O'Brien-Fleming type 1 error spending function.



2.  Secondary:   Time to Progression Free Survival (PFS)   [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ]

3.  Secondary:   Overall Tumor Response   [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ]

4.  Secondary:   Time to Tumor Progression   [ Time Frame: From the date of randomization up to 104 weeks (study cut-off) ]

5.  Secondary:   Time to Prostatic Specific Antigen (PSA) Progression   [ Time Frame: at screening, day 1 of every treatment cycle, up to 104 weeks (study cut-off) ]

6.  Secondary:   PSA (Prostate-Specific Antigen) Response   [ Time Frame: from baseline up to 104 weeks (study cut-off) ]

7.  Secondary:   Time to Pain Progression   [ Time Frame: from baseline up to 104 weeks (study cut-off) ]

8.  Secondary:   Pain Response   [ Time Frame: from baseline up to 104 weeks (study cut-off) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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