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Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy (PALETTE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00753688
First received: September 12, 2008
Last updated: August 15, 2013
Last verified: August 2013
Results First Received: November 17, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Sarcoma, Soft Tissue
Interventions: Drug: PAZOPANIB
Drug: Placebo

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Pazopanib Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent

Participant Flow:   Overall Study
    Placebo     Pazopanib  
STARTED     123     246  
Ongoing - in Follow-up     15     31  
COMPLETED     0     0  
NOT COMPLETED     123     246  
Death                 102                 203  
Missing                 4                 9  
Participant Withdrew Consent                 2                 2  
Ongoing - in Follow-up                 15                 31  
Adverse Event                 0                 1  



  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.
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Reporting Groups
  Description
Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Pazopanib Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Total Total of all reporting groups

Baseline Measures
    Placebo     Pazopanib     Total  
Number of Participants  
[units: participants]
  123     246     369  
Age  
[units: Years]
Mean ± Standard Deviation
  51.7  ± 13.77     54.0  ± 14.92     53.2  ± 14.57  
Gender  
[units: Participants]
     
Female     69     147     216  
Male     54     99     153  
Race/Ethnicity, Customized  
[units: participants]
     
African American/African Heritage     2     4     6  
American Indian or Alaska Native     0     1     1  
Asian - Central/South Asian Heritage     2     0     2  
Asian - East Asian Heritage     7     24     31  
Asian - Japanese Heritage     16     31     47  
Asian - South East Asian Heritage     2     2     4  
White - Arabic/North African Heritage     2     1     3  
White - White/Caucasian/European Heritage     89     174     263  
Mixed Race     1     0     1  
Unknown     2     9     11  
Number of participants in the indicated soft tissue sarcoma (STS) subgroups at Baseline [1]
[units: participants]
     
Leiomyosarcoma     49     109     158  
Synovial sarcoma     13     25     38  
Other STS histologies     61     112     173  
[1] Participants were categorized in the following histology subgroups of STS (as per the World Health Organization [WHO] classification, 2008): leiomyosarcoma, defined as malignant cancer of smooth muscle; synovial sarcoma, defined as cancer near the joints of the arm or leg; and other STS, defined as sarcoma without the tumor type of leiomyosarcoma or synovial sarcoma.



  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS)   [ Time Frame: From the date of randomization until the date of the first documented radiological progression or date of death from any cause, whichever came first (assessed for an average of 10 months) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: From the date of randomization until 215 deaths (assessed for an average of 12 months) ]

3.  Secondary:   Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator   [ Time Frame: From the start of treatment until disease progression (assessed for an average of 10 months) ]

4.  Secondary:   Time to Response Assessed by an Independent Radiologist and the Investigator   [ Time Frame: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months) ]

5.  Secondary:   Duration of Response Assessed by the Independent Radiologist and the Investigator   [ Time Frame: From the date of randomization until the date of the first documented evidence of CR or PR (assessed for an average of 10 months) ]

6.  Secondary:   PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)   [ Time Frame: From the date of randomization until the date of the first documented progression or the date of death from any cause, whichever came first (assessed for an average of 10 months) ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
Measure Description PFS was defined as the time interval between the date of randomization and the earliest date of either disease progression or death due to any cause. Participants were analyzed for PFS in histology subgroups of STS (as per the World Health Organization [WHO] classification, 2008): leiomyosarcoma (malignant cancer of smooth muscle), synovial sarcoma (cancer near the joints of the arm or leg), and other STS (without the tumor type of leiomyosarcoma or synovial sarcoma), based on independent review.The Kaplan-Meier method was used for PFS estimates.
Time Frame From the date of randomization until the date of the first documented progression or the date of death from any cause, whichever came first (assessed for an average of 10 months)  
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. The "n"s in the category titles represent the number of participants in each treatment arm with the indicated STS.

Reporting Groups
  Description
Placebo Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent
Pazopanib Pazopanib 200 milligrams (mg) and 400 mg film-coated tablets (containing pazopanib monohydrochloride) administered orally at a dose of 800 mg once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent

Measured Values
    Placebo     Pazopanib  
Number of Participants Analyzed  
[units: participants]
  123     246  
PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)  
[units: weeks]
Median ( 95% Confidence Interval )
   
Leiomyosarcoma, n=49, 109     8.1  
  ( 7.6 to 9.3 )  
  20.1  
  ( 13.3 to 23.1 )  
Synovial sarcoma, n=13, 25     4.1  
  ( 3.7 to 8.9 )  
  17.9  
  ( 8.9 to 27.1 )  
Other STS, n=61, 112     4.3  
  ( 4.0 to 7.9 )  
  20.1  
  ( 13.0 to 27.1 )  


Statistical Analysis 1 for PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.37
95% Confidence Interval ( 0.23 to 0.60 )
[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:
  Stratified two-sided log rank p-value for leiomyosarcoma
[4] Other relevant estimation information:
  The HR was adjusted for World Health Organization (WHO) performance status scale (0 versus 1 at Baseline) and number of prior lines of systemic treatment for advanced disease (0/1 versus 2+).

Statistical Analysis 2 for PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.005
Hazard Ratio (HR) [4] 0.43
95% Confidence Interval ( 0.19 to 0.98 )
[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:
  Stratified two-sided log rank p-value for synovial sarcoma
[4] Other relevant estimation information:
  The HR was adjusted for World Health Organization (WHO) performance status scale (0 versus 1 at Baseline) and number of prior lines of systemic treatment for advanced disease (0/1 versus 2+).

Statistical Analysis 3 for PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.39
95% Confidence Interval ( 0.25 to 0.60 )
[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:
  Stratified two-sided log rank p-value for other STS histologies
[4] Other relevant estimation information:
  The HR was adjusted for World Health Organization (WHO) performance status scale (0 versus 1 at Baseline) and number of prior lines of systemic treatment for advanced disease (0/1 versus 2+).



7.  Secondary:   Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104 ]

8.  Secondary:   Change From Baseline in Heart Rate   [ Time Frame: Baseline, Day 8, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 88, 96, and 104 ]

9.  Secondary:   Number of Participants With the Indicated Grade Shifts From Baseline Grade for Hemoglobin Level, Lymphocyte Count, White Blood Cell Count, Neutrophil Count, and Platelet Count   [ Time Frame: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks) ]

10.  Secondary:   Number of Participants With the Indicated Grade Shifts From Baseline Grade for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Creatinine, Hyper/Hypoglycemia, Hyper/Hypokalemia, Hyper/Hyponatremia, and Total Bilirubin   [ Time Frame: From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks) ]

11.  Secondary:   Number of Participants With the Indicated Absolute Percent Change From Baseline (BL) in Left Ventricular Ejection Fraction (LVEF) at Any Time Post-BL (Worst Case On-therapy)   [ Time Frame: Baseline (within 14 days of the first dose of study drug) and any time post-baseline until study drug discontinuation or end of treatment (assessed for an average of 20 weeks) ]


  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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