A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00075218
First received: January 6, 2004
Last updated: August 31, 2009
Last verified: August 2009
Results First Received: May 6, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Gastrointestinal Stromal Tumor
Interventions: Drug: Placebo
Drug: SU011248

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment began (medical clinic) in December 2003. Study was unblinded on 27 January 2005 (end of Double-blind treatment). Subjects experiencing disease progression could crossover to Open-label treatment. Open-label data collection ended May 2008.

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

361 subjects randomized to double-blind treatment in 2:1 ratio (sunitinib vs. Placebo).

255 subjects continued on or crossed over to Open-label treatment.


Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Sunitinib Open-Label Treatment Subjects experiencing disease progression could have their treatment assignment unblinded, and subjects who had been receiving placebo could crossover to open-label treatment with sunitinib; subjects who had been receiving sunitinib during double-blind treatment of the study could continue to do so after unblinding if, in the opinion of the investigator, there was sufficient evidence of clinical benefit.

Participant Flow for 2 periods

Period 1:   Double-Blind Treatment
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
STARTED     243 [1]   118 [1]   0  
Received Double-Blind Treatment     228 [2]   114 [2]   0  
Crossed Over to Open-Label Treatment     152     103     0  
COMPLETED     152 [3]   103 [3]   0  
NOT COMPLETED     91     15     0  
Adverse Event                 23                 4                 0  
Withdrawal by Subject                 7                 4                 0  
Lost to Follow-up                 1                 0                 0  
Lack of Efficacy                 58                 6                 0  
Decision of Sponsor                 0                 1                 0  
No study medication taken                 2                 0                 0  
[1] Intent To Treat Population (ITT)
[2] As Treated Population (AT)
[3] Defined:subjects completed double-blind treatment phase and/or entered open-label treatment phase.

Period 2:   Open-Label Treatment
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
STARTED     0     0     255  
COMPLETED     0     0     0  
NOT COMPLETED     0     0     255  
Lack of Efficacy                 0                 0                 174  
Adverse Event                 0                 0                 51  
Withdrawal by Subject                 0                 0                 12  
Decision of Sponsor                 0                 0                 8  
Protocol Violation                 0                 0                 1  
enrolled in a separate continuation                 0                 0                 9  



  Baseline Characteristics
  Hide 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
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Total Total of all reporting groups

Baseline Measures
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Total  
Number of Participants  
[units: participants]
  243     118     361  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     170     81     251  
>=65 years     73     37     110  
Gender  
[units: participants]
     
Female     91     71     162  
Male     152     47     199  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase   [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase ]

Measure Type Primary
Measure Title Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase
Measure Description Time from randomization to first documentation of objective tumor progression based on the assessment of an independent, third-party imaging laboratory using RECIST (Response Evaluation Criteria in Solid Tumors).
Time Frame Day 28 of each 6-week cycle : duration of double-blind treatment phase  
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.
From the Intent to Treat (ITT) population, 82 subjects on sunitinib treatment were observed to have disease progression during blinded phase and were included in TTP analysis. 67 subjects on placebo were observed to have disease progression during blinded phase.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  207     105  
Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase  
[units: weeks]
Median ( 95% Confidence Interval )
  27.3  
  ( 16.0 to 32.1 )  
  6.4  
  ( 4.4 to 10 )  


Statistical Analysis 1 for Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.329
95% Confidence Interval ( 0.233 to 0.466 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The study was designed to test the null hypothesis that the median TTP from placebo treatment is 4 months versus the alternative hypothesis that the median TTP from sunitinib treatment is at least 6 months with an overall 2-sided significance level of 0.05 and power of 90%.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  two-sided unstratified log-rank test
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The nominal levels of significance for the interim and final analyses were determined at the time of the analyses using the Lan-DeMets procedure with an O’Brien-Fleming stopping rule.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study   [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV) ]

Measure Type Primary
Measure Title Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study
Measure Description Time from randomization to first documentation of objective tumor progression based on the assessment of an independent, third-party imaging laboratory using RECIST (Response Evaluation Criteria in Solid Tumors).
Time Frame Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV)  
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.
From the Intent to Treat (ITT) population, 91 subjects on sunitinib treatment were observed to have disease progression during blinded phase and were included in TTP analysis. 73 subjects on placebo were observed to have disease progression during blinded phase.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study  
[units: weeks]
Median ( 95% Confidence Interval )
  26.6  
  ( 16.0 to 32.1 )  
  6.4  
  ( 4.4 to 10.0 )  


Statistical Analysis 1 for Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.339
95% Confidence Interval ( 0.244 to 0.472 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  two-sided unstratified log-rank test
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.327
95% Confidence Interval ( 0.232 to 0.460 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Stratified log-rank test
[2] Other relevant method information, such as adjustments or degrees of freedom:
  log—rank test of treatment stratified by prior imatinib mesylate response and McGill Pain Questionnaire's Present Pain Intensity score
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Progression Free Survival (PFS)
Measure Description Time from randomization to first documentation of objective tumor progression or to death due to any cause (on treatment or within 28 days of last dose).
Time Frame Day 28 of each cycle : duration of double-blind treatment phase  
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.
ITT population

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Progression Free Survival (PFS)  
[units: weeks]
Median ( 95% Confidence Interval )
  22.9  
  ( 10.9 to 28.0 )  
  6.0  
  ( 4.4 to 9.7 )  


Statistical Analysis 1 for Progression Free Survival (PFS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.347
95% Confidence Interval ( 0.253 to 0.475 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No p-value adjustment for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Overall Survival Status of Subjects   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

Measure Type Secondary
Measure Title Overall Survival Status of Subjects
Measure Description Number of subjects alive at end of study.
Time Frame clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug  
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.
ITT population.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Overall Survival Status of Subjects  
[units: participants]
   
Dead     176     90  
Alive     67     28  

No statistical analysis provided for Overall Survival Status of Subjects



5.  Secondary:   Overall Survival   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description Time from date of randomization to date of death due to any cause.
Time Frame clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug  
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.
ITT population; Number subjects Dead = 176, 90 (sunitinib, placebo respectively). Subjects who were not known to be dead at the time the database was closed for analysis were censored on the date they were last known to be alive.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Overall Survival  
[units: weeks]
Median ( 95% Confidence Interval )
  72.7  
  ( 61.3 to 83.0 )  
  64.9  
  ( 45.7 to 96.0 )  


Statistical Analysis 1 for Overall Survival
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.306
Hazard Ratio (HR) [4] 0.876
95% Confidence Interval ( 0.679 to 1.129 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No p-value adjustment for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



6.  Secondary:   Overall Survival Based on the Rank Preserving Structural Failure Time Method   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

Measure Type Secondary
Measure Title Overall Survival Based on the Rank Preserving Structural Failure Time Method
Measure Description time from date of randomization to date of death due to any cause (rank preserving structural failure time method).
Time Frame clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug  
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.
ITT population

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Overall Survival Based on the Rank Preserving Structural Failure Time Method  
[units: weeks]
Median ( 95% Confidence Interval )
  72.7  
  ( 61.3 to 83.0 )  
  39.0  
  ( 28.0 to 54.1 )  


Statistical Analysis 1 for Overall Survival Based on the Rank Preserving Structural Failure Time Method
Groups [1] All groups
Method [2] Rank Preserving Structural Failure Time
P Value [3] 0.306
Hazard Ratio (HR) [4] 0.505
95% Confidence Interval ( 0.262 to 1.134 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No p-value adjustment for multiple comparisons.
[4] Other relevant estimation information:
  95% CI for Hazard Ratio is from 2.5% and 97.5% Empirical Percentiles of 100,000 Bootstraps.



7.  Secondary:   Best Overall Tumor Response During Double-blind Treatment Phase   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Best Overall Tumor Response During Double-blind Treatment Phase
Measure Description Tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame Day 28 of each cycle : duration of double-blind treatment phase  
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.
ITT population

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Best Overall Tumor Response During Double-blind Treatment Phase  
[units: participants]
   
Complete Response (CR)     0     0  
Partial Response (PR)     16     0  
Stable Disease     128     50  
Progressive Disease     45     44  
Unable to Evaluate     1     0  
Missing     53     24  

No statistical analysis provided for Best Overall Tumor Response During Double-blind Treatment Phase



8.  Secondary:   Confirmed Objective Response (CR or PR) in Subjects   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Confirmed Objective Response (CR or PR) in Subjects
Measure Description Overall confirmed objective response = confirmed Complete Response (CR) OR confirmed Partial Response (PR) according to RECIST. Confirmed responses were those that persisted on repeat imaging study ≥ 4 weeks after initial documentation of response.
Time Frame Day 28 of each cycle : duration of double-blind treatment phase  
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.
ITT population.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Confirmed Objective Response (CR or PR) in Subjects  
[units: participants]
  16     0  


Statistical Analysis 1 for Confirmed Objective Response (CR or PR) in Subjects
Groups [1] Sunitinib Double-Blind Treatment
rate (percentage) [2] 6.6
95% Confidence Interval ( 3.8 to 10.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  Used exact method based on binomial distribution.

Statistical Analysis 2 for Confirmed Objective Response (CR or PR) in Subjects
Groups [1] All groups
Method [2] Pearson chi-square test
P Value [3] 0.004
Treatment Difference (%) [4] 6.58
95% Confidence Interval ( 3.47 to 9.70 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No p-value adjustment for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



9.  Secondary:   Time to Tumor Response (TTR)   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Time to Tumor Response (TTR)
Measure Description Time from date of randomization to first documentation of objective tumor response that was subsequently confirmed. TTR was only calculated for the subgroup of subjects with a confirmed objective tumor response.
Time Frame Day 28 of each cycle : duration of double-blind treatment phase  
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.
ITT population. Number of subjects analyzed = number of subjects with tumor response.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  16     0  
Time to Tumor Response (TTR)  
[units: weeks]
Median ( 95% Confidence Interval )
  13.4  
  ( 9.9 to 16.1 )  
   
   

No statistical analysis provided for Time to Tumor Response (TTR)



10.  Secondary:   Duration of Performance Status Maintenance   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Duration of Performance Status Maintenance
Measure Description Time from randomization until the last time the performance status was no worse than at baseline or to death due to cancer in the absence of previous documentation of performance status worsening.
Time Frame Day 28 of each cycle : duration of double-blind treatment phase  
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.
ITT Population. Number of subjects at median observed to have status worsening or died before status worsening.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  106     0  
Duration of Performance Status Maintenance  
[units: weeks]
Median ( 95% Confidence Interval )
  18.9  
  ( 12.1 to 31.1 )  
   
   

No statistical analysis provided for Duration of Performance Status Maintenance



11.  Secondary:   Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)
Measure Description 25th Quartile: Time to Progression. Progression: a) No change (NC) in MPQ-PPI score (0=no pain to 5=excruciating pain) with increase total analgesic use >= 50% over baseline OR b) Increase score >= 1 point with either NC in total analgesic use or increase total analgesic use >= 50% over baseline. (50th Quartile not achieved.)
Time Frame Day 1 & 28 of each cycle : duration of double-blind treatment phase  
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.
Pain-Relief-Response population. Subjects at 25th Quartile with pain progress during blinded phase.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  37     0  
Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)  
[units: weeks (25th Quartile)]
Median ( 95% Confidence Interval )
  12.1  
  ( 6.1 to 27.1 )  
   
   


Statistical Analysis 1 for Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.9322
Hazard Ratio (HR) [4] 0.972
95% Confidence Interval ( 0.508 to 1.860 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  2-sided, unstratified log-rank test
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



12.  Secondary:   Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)
Measure Description MPQ-PPI: 0=no pain to 5= excruciating pain. Pain Relief Response= 1) Decrease by >= 1 points in MPQ-PPI score with either Decrease or No Change in total analgesic use >= 50% over baseline OR 2) No change in MPQ-PPI score with Decrease total analgesic use >= 50% over baseline.
Time Frame Day 1 & 28 of each cycle : duration of double-blind treatment phase  
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.
Pain-Relief-Response population.

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  150     75  
Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)  
[units: participants]
  46     10  


Statistical Analysis 1 for Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)
Groups [1] All groups
Method [2] Pearson chi-square
P Value [3] 0.0046
Treatment Difference (percent) [4] 17.3
95% Confidence Interval ( 6.7 to 28.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  95% CI of Difference based on normal distribution. Percent = (number of subjects with response per total subjects per treatment in defined analysis population)*100.



13.  Secondary:   Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)
Measure Description Change: median score at observation minus median score at baseline. EQ-VAS score on the self-rated “thermometer,” indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state.
Time Frame Day 1 & 28 of each cycle : duration of double-blind treatment phase  
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.
ITT population. Number subjects with evaluable data: (n=sunitinib, placebo)

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)  
[units: score on scale]
Median ( Full Range )
   
Cycle 1 Day 28 (n=187, 89)     -3.0  
  ( -60.0 to 70.0 )  
  0.0  
  ( -50.0 to 45.0 )  
Cycle 2 Day 1 (n=148, 53)     0.0  
  ( -60.0 to 55.0 )  
  0.0  
  ( -30.0 to 41.0 )  
Cycle 2 Day 28 (n=132, 41)     -4.5  
  ( -50.0 to 55.0 )  
  0.0  
  ( -80.0 to 40.0 )  
Cycle 3 Day 1 (n=102,16)     0.0  
  ( -58.0 to 32.0 )  
  0.0  
  ( -75.0 to 34.0 )  
Cycle 3 Day 28 (n=91,13)     -5.0  
  ( -55.0 to 42.0 )  
  -1.0  
  ( -75.0 to 16.0 )  
Cycle 4 Day 1 (n=73,10)     0.0  
  ( -65.0 to 40.0 )  
  5.0  
  ( -10.0 to 15.0 )  

No statistical analysis provided for Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)



14.  Secondary:   Change From Baseline in EQ-5D Health State Profile Index   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

Measure Type Secondary
Measure Title Change From Baseline in EQ-5D Health State Profile Index
Measure Description Change: median index score at observation minus median index score at baseline. EQ-5D is a generic instrument that describes health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) with a weighted health Index based on general population values where where 0.0 = death and 1.0 = perfect health.
Time Frame Day 1 & 28 of each cycle : duration of double-blind treatment phase  
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.
ITT Population. Number subjects with evaluable data: (n=sunitinib, placebo)

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment  
Number of Participants Analyzed  
[units: participants]
  243     118  
Change From Baseline in EQ-5D Health State Profile Index  
[units: score on scale]
Median ( Full Range )
   
Cycle 1 Day 28 (n=185, 87)     0.000  
  ( -1.008 to 0.736 )  
  0.000  
  ( -0.655 to 0.532 )  
Cycle 2 Day 1 (n=149, 53)     0.000  
  ( -1.244 to 0.603 )  
  0.000  
  ( -0.603 to 0.434 )  
Cycle 2 Day 28 (n=129, 41)     -0.017  
  ( -1.008 to 0.603 )  
  0.000  
  ( -0.694 to 0.655 )  
Cycle 3 Day 1 (n=104, 17)     0.000  
  ( -0.694 to 0.639 )  
  0.000  
  ( -0.655 to 0.192 )  
Cycle 3 Day 28 (n=91, 13)     -0.036  
  ( -1.175 to 0.736 )  
  0.000  
  ( -0.655 to 0.204 )  
Cycle 4 Day 1 (n=74, 10)     0.000  
  ( -0.768 to 0.603 )  
  0.059  
  ( -0.152 to 0.275 )  

No statistical analysis provided for Change From Baseline in EQ-5D Health State Profile Index




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
Duration of Tumor Response could not be reliably estimated at the time of analysis.


  More Information