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
No text entered.

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
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.
No text entered.

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) ]

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
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Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from Baseline through End of Study (average of 20 study weeks).
Additional Description The Safety Population, comprised of all participants who had started their allocated treatment (at least one dose of the study drug), was used for all safety analyses.

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

Serious Adverse Events
    Placebo     Pazopanib  
Total, serious adverse events      
# participants affected / at risk     29/123 (23.58%)     99/240 (41.25%)  
Blood and lymphatic system disorders      
Febrile neutropenia † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Thrombotic microangiopathy † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Cardiac disorders      
Left ventricular dysfunction † 1    
# participants affected / at risk     0/123 (0.00%)     5/240 (2.08%)  
Atrial fibrillation † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Atrial flutter † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Cardio-respiratory arrest † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Myocardial infarction † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Pericardial effusion † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Sinus bradycardia † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Gastrointestinal disorders      
Gastrointestinal pain † 1    
# participants affected / at risk     2/123 (1.63%)     4/240 (1.67%)  
Vomiting † 1    
# participants affected / at risk     1/123 (0.81%)     4/240 (1.67%)  
Colonic obstruction † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Nausea † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Small intestinal obstruction † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Constipation † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Diarrhea † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Duodenal ulcer † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Enterocutaneous fistula † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Gastric stenosis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Gastrointestinal fistula † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Hematemesis † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Ileus † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Peritoneal hemorrhage † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Upper gastrointestinal hemorrhage † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Oesophageal haemorrhage † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Oesophageal stenosis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Oesophageal haemorrhage † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Oesophageal stenosis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
General disorders      
Fatigue † 1    
# participants affected / at risk     1/123 (0.81%)     5/240 (2.08%)  
Chest pain † 1    
# participants affected / at risk     0/123 (0.00%)     4/240 (1.67%)  
Pyrexia † 1    
# participants affected / at risk     3/123 (2.44%)     1/240 (0.42%)  
Performance status decreased † 1    
# participants affected / at risk     0/123 (0.00%)     3/240 (1.25%)  
Disease progression † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Asthenia † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Death † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Localized edema † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Multi-organ failure † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Mass † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Mass † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Immune system disorders      
Hypersensitivity † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     0/123 (0.00%)     4/240 (1.67%)  
Sepsis † 1    
# participants affected / at risk     1/123 (0.81%)     2/240 (0.83%)  
Abscess † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Biliary tract infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Candida sepsis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Clostridial infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Cystitis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Device related infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Diverticulitis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Gastroenteritis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Infective tenosynovitis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Lactobacillus infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Lung infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Pelvic abscess † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Pyelonephritis † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Skin infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Streptococcal sepsis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Superinfection bacterial † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Tooth abscess † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Wound infection † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Wound infection pseudomonas † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Bacterial sepsis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Bacterial sepsis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Injury, poisoning and procedural complications      
Femur fracture † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Radiation injury † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Radiation skin injury † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Vascular graft thrombosis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     1/123 (0.81%)     9/240 (3.75%)  
Hemoglobin decreased † 1    
# participants affected / at risk     2/123 (1.63%)     8/240 (3.33%)  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     0/123 (0.00%)     6/240 (2.50%)  
Gamma-glutamyltransferase increased † 1    
# participants affected / at risk     0/123 (0.00%)     6/240 (2.50%)  
Platelet count decreased † 1    
# participants affected / at risk     1/123 (0.81%)     3/240 (1.25%)  
Blood bilirubin increased † 1    
# participants affected / at risk     1/123 (0.81%)     2/240 (0.83%)  
Neutrophil percentage † 1    
# participants affected / at risk     1/123 (0.81%)     2/240 (0.83%)  
Alanine aminotransferase † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Aspartate aminotransferase † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Blood potassium decreased † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Lymphocyte percentage † 1    
# participants affected / at risk     2/123 (1.63%)     0/240 (0.00%)  
Neutrophil count decreased † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Bilirubin conjugated † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Blood cholesterol abnormal † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Blood lactate dehydrogenase increased † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Hemoglobin † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Neutrophil percentage decreased † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Urine protein/creatinine ratio † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
White blood cell count decreased † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Dehydration † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Hypercalcemia † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Hypoglycemia † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Lactic acidosis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Musculoskeletal and connective tissue disorders      
Myalgia † 1    
# participants affected / at risk     1/123 (0.81%)     2/240 (0.83%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Musculoskeletal pain † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Rhabdomyolysis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Tendonitis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Tendonitis † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Tumor pain † 1    
# participants affected / at risk     3/123 (2.44%)     4/240 (1.67%)  
Malignant pleural effusion † 1    
# participants affected / at risk     1/123 (0.81%)     2/240 (0.83%)  
Leiomyosarcoma metastatic † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Metastases to skin † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Neoplasm † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Nervous system disorders      
Peripheral sensory neuropathy † 1    
# participants affected / at risk     1/123 (0.81%)     1/240 (0.42%)  
Cerebral infarction † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Hemorrhage intracranial † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Headache † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Peripheral motor neuropathy † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Subarachnoid hemorrhage † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Syncope † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Psychiatric disorders      
Confusional state † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Depressed mood † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Renal and urinary disorders      
Renal failure † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Hematuria † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Nephrolithiasis † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Nephrotic syndrome † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Respiratory, thoracic and mediastinal disorders      
Dyspnea † 1    
# participants affected / at risk     3/123 (2.44%)     9/240 (3.75%)  
Pneumothorax † 1    
# participants affected / at risk     0/123 (0.00%)     6/240 (2.50%)  
Pleural effusion † 1    
# participants affected / at risk     1/123 (0.81%)     4/240 (1.67%)  
Lung disorder † 1    
# participants affected / at risk     0/123 (0.00%)     2/240 (0.83%)  
Respiratory failure † 1    
# participants affected / at risk     2/123 (1.63%)     0/240 (0.00%)  
Acute respiratory distress syndrome † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Hemoptysis † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Pulmonary hemorrhage † 1    
# participants affected / at risk     1/123 (0.81%)     0/240 (0.00%)  
Skin and subcutaneous tissue disorders      
Skin ulcer † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Vascular disorders      
Embolism arterial † 1    
# participants affected / at risk     2/123 (1.63%)     6/240 (2.50%)  
Hemorrhage † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Ischemia † 1    
# participants affected / at risk     0/123 (0.00%)     1/240 (0.42%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA




  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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