Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma (COMPARZ)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00720941
First received: July 22, 2008
Last updated: June 19, 2014
Last verified: February 2014
Results First Received: January 4, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Renal Cell
Interventions: Drug: Pazopanib
Drug: Sunitinib

  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
Per protocol amendment, the number of participants (par.) was increased to ~1100 (including all par. enrolled in Studies VEG108844 and VEG113078 [NCT01147822; a substudy in Asian par.]). This summary is a pooled analysis of both studies. 1110 par. were analyzed; 927 from VEG108844 (reflected in the protocol enrollment field), 183 from VEG113078.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were stratified based on Karnofsky Performance Scale scores (70 or 80; 90 or 100), Baseline levels of lactate dehydrogenase (>1.5 versus <=1.5 times the upper limit of normal [ULN]), and previous nephrectomy (yes versus no) and were randomized in a 1:1 ratio to receive either pazopanib or sunitinib.

Reporting Groups
  Description
Pazopanib 800 mg Participants were administered pazopanib 800 milligrams (mg) (2 x 400 mg tablets) orally once daily (OD) continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

Participant Flow:   Overall Study
    Pazopanib 800 mg     Sunitinib 50 mg  
STARTED     557     553  
Ongoing     34     23  
COMPLETED     144     138  
NOT COMPLETED     413     415  
Death                 334                 335  
Protocol Violation                 0                 2  
Lost to Follow-up                 17                 15  
Physician Decision                 1                 5  
Withdrawal by Subject                 27                 35  
Ongoing                 34                 23  



  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
Pazopanib 800 mg Participants were administered pazopanib 800 mg (2 x 400 mg tablets) orally OD continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Total Total of all reporting groups

Baseline Measures
    Pazopanib 800 mg     Sunitinib 50 mg     Total  
Number of Participants  
[units: participants]
  557     553     1110  
Age  
[units: Years]
Mean ± Standard Deviation
  60.9  ± 10.89     61.2  ± 10.98     61.1  ± 10.93  
Gender  
[units: Participants]
     
Female     159     138     297  
Male     398     415     813  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     10     5     15  
American Indian or Alaska Native     3     0     3  
Asian     194     188     382  
White     349     358     707  
American Indian or Alaska Native & White     0     1     1  
Unknown     1     1     2  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression-free Survival (PFS)   [ Time Frame: From randomization until the earliest date of disease progression or death (up to Study Week 191) ]

2.  Secondary:   Overall Survival   [ Time Frame: From randomization until death (up to Study Week 268) ]

3.  Secondary:   Number of Participants in the Indicated Categories for Overall Response as Assessed by Independent Review   [ Time Frame: From randomization until the time of a confirmed best response of CR or PR (up to Study Week 167) ]

4.  Secondary:   Time to Response   [ Time Frame: From randomization until the time of the first documented confirmed complete or partial response (up to Study Week 167) ]

5.  Secondary:   Duration of Response (DOR)   [ Time Frame: From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (up to Study Week 167) ]

6.  Secondary:   Number of Participants (Par.) With Serious Adverse Events (SAEs)/Non-serious Adverse Events (Any Untoward Medical Occurrence in a Par. Administered a Pharmaceutical Product and Which Does Not Necessarily Have a Causal Relationship With This Treatment)   [ Time Frame: From the time of the first dose of study drug to approximately one month after the discontinuation of study drug (up to Study Week 268) ]

7.  Secondary:   Change From Baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) Scale Scores at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline (predose); Weeks 4, 10, 16, and 22 ]

8.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Disease-related Symptoms-physical (DRS-P) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

9.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Disease Related Symptoms-emotional (DRS-E) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

10.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Treatment Side Effects (TSE) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

11.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Functional Well Being (FWB) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

12.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Total Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

13.  Secondary:   Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Scale Worst Soreness Scores at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

14.  Secondary:   Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Mouth and Throat Soreness Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

15.  Secondary:   Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Foot Soreness Scores at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

16.  Secondary:   Summary of Analysis for the Cancer Treatment Satisfaction Questionnaire (CTSQ) Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Weeks 4, 10, 16, and 22 ]

17.  Secondary:   Medical Resource Utilization (MRU): Assessed as the Mean Number of Non-study Medical Visits, Telephone Consultations, Hospital Days, and Emergency Room (ER) Visits Per 30 Days Through Week 24   [ Time Frame: From Day 1 up to Week 24 ]

18.  Secondary:   MRU: The Mean Number of Laboratory Visits, Radiology Visits, Home Healthcare Visits, and Medical Procedures for Cycles 1-4. MRU Data Collected at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Weeks 4, 10, 16, and 22 ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame Participants were analyzed from the time of the first dose of study drug to approximately one month after the discontinuation of study drug (up to Study Week 268).
Additional Description Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication, according to the actual treatment received.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Pazopanib 800 mg Participants were administered pazopanib 800 mg (2 x 400 mg tablets) orally OD continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

Other Adverse Events
    Pazopanib 800 mg     Sunitinib 50 mg  
Total, other (not including serious) adverse events      
# participants affected / at risk     541/554     535/548  
Blood and lymphatic system disorders      
Neutropenia † 1    
# participants affected / at risk     60/554 (10.83%)     146/548 (26.64%)  
Thrombocytopenia † 1    
# participants affected / at risk     56/554 (10.11%)     180/548 (32.85%)  
Leukopenia † 1    
# participants affected / at risk     51/554 (9.21%)     99/548 (18.07%)  
Anaemia † 1    
# participants affected / at risk     36/554 (6.50%)     99/548 (18.07%)  
Endocrine disorders      
Hypothyroidism † 1    
# participants affected / at risk     71/554 (12.82%)     136/548 (24.82%)  
Hyperthyroidism † 1    
# participants affected / at risk     7/554 (1.26%)     29/548 (5.29%)  
Eye disorders      
Eyelid oedema † 1    
# participants affected / at risk     19/554 (3.43%)     42/548 (7.66%)  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     349/554 (63.00%)     312/548 (56.93%)  
Nausea † 1    
# participants affected / at risk     246/554 (44.40%)     249/548 (45.44%)  
Vomiting † 1    
# participants affected / at risk     157/554 (28.34%)     148/548 (27.01%)  
Constipation † 1    
# participants affected / at risk     97/554 (17.51%)     133/548 (24.27%)  
Dyspepsia † 1    
# participants affected / at risk     80/554 (14.44%)     134/548 (24.45%)  
Stomatitis † 1    
# participants affected / at risk     78/554 (14.08%)     153/548 (27.92%)  
Abdominal pain † 1    
# participants affected / at risk     70/554 (12.64%)     72/548 (13.14%)  
Abdominal pain upper † 1    
# participants affected / at risk     70/554 (12.64%)     48/548 (8.76%)  
Abdominal distension † 1    
# participants affected / at risk     33/554 (5.96%)     24/548 (4.38%)  
Flatulence † 1    
# participants affected / at risk     32/554 (5.78%)     15/548 (2.74%)  
Dry mouth † 1    
# participants affected / at risk     26/554 (4.69%)     29/548 (5.29%)  
Abdominal discomfort † 1    
# participants affected / at risk     24/554 (4.33%)     34/548 (6.20%)  
Mouth ulceration † 1    
# participants affected / at risk     23/554 (4.15%)     37/548 (6.75%)  
Gastrooesophageal reflux disease † 1    
# participants affected / at risk     20/554 (3.61%)     57/548 (10.40%)  
General disorders      
Fatigue † 1    
# participants affected / at risk     305/554 (55.05%)     343/548 (62.59%)  
Mucosal inflammation † 1    
# participants affected / at risk     61/554 (11.01%)     141/548 (25.73%)  
Oedema peripheral † 1    
# participants affected / at risk     56/554 (10.11%)     85/548 (15.51%)  
Asthenia † 1    
# participants affected / at risk     48/554 (8.66%)     58/548 (10.58%)  
Pyrexia † 1    
# participants affected / at risk     47/554 (8.48%)     77/548 (14.05%)  
Chills † 1    
# participants affected / at risk     15/554 (2.71%)     43/548 (7.85%)  
Oedema † 1    
# participants affected / at risk     16/554 (2.89%)     36/548 (6.57%)  
Face oedema † 1    
# participants affected / at risk     12/554 (2.17%)     40/548 (7.30%)  
Infections and infestations      
Nasopharyngitis † 1    
# participants affected / at risk     46/554 (8.30%)     46/548 (8.39%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     30/554 (5.42%)     34/548 (6.20%)  
Urinary tract infection † 1    
# participants affected / at risk     22/554 (3.97%)     29/548 (5.29%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     143/554 (25.81%)     93/548 (16.97%)  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     131/554 (23.65%)     98/548 (17.88%)  
Weight decreased † 1    
# participants affected / at risk     85/554 (15.34%)     33/548 (6.02%)  
Blood creatinine increased † 1    
# participants affected / at risk     59/554 (10.65%)     93/548 (16.97%)  
Blood bilirubin increased † 1    
# participants affected / at risk     51/554 (9.21%)     35/548 (6.39%)  
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     40/554 (7.22%)     30/548 (5.47%)  
Lipase increased † 1    
# participants affected / at risk     42/554 (7.58%)     32/548 (5.84%)  
Blood lactate dehydrogenase increased † 1    
# participants affected / at risk     40/554 (7.22%)     60/548 (10.95%)  
Platelet count decreased † 1    
# participants affected / at risk     36/554 (6.50%)     97/548 (17.70%)  
Amylase increased † 1    
# participants affected / at risk     37/554 (6.68%)     24/548 (4.38%)  
Haemoglobin decreased † 1    
# participants affected / at risk     34/554 (6.14%)     5/548 (0.91%)  
Blood thyroid stimulating hormone increased † 1    
# participants affected / at risk     32/554 (5.78%)     66/548 (12.04%)  
White blood cell count decreased † 1    
# participants affected / at risk     31/554 (5.60%)     74/548 (13.50%)  
Neutrophil count decreased † 1    
# participants affected / at risk     27/554 (4.87%)     62/548 (11.31%)  
Blood triglycerides increased † 1    
# participants affected / at risk     21/554 (3.79%)     35/548 (6.39%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     207/554 (37.36%)     203/548 (37.04%)  
Hypophosphataemia † 1    
# participants affected / at risk     21/554 (3.79%)     32/548 (5.84%)  
Hyponatraemia † 1    
# participants affected / at risk     22/554 (3.97%)     36/548 (6.57%)  
Hyperglycaemia † 1    
# participants affected / at risk     16/554 (2.89%)     30/548 (5.47%)  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     90/554 (16.25%)     89/548 (16.24%)  
Arthralgia † 1    
# participants affected / at risk     77/554 (13.90%)     67/548 (12.23%)  
Pain in extremity † 1    
# participants affected / at risk     68/554 (12.27%)     93/548 (16.97%)  
Musculoskeletal pain † 1    
# participants affected / at risk     43/554 (7.76%)     28/548 (5.11%)  
Muscle spasms † 1    
# participants affected / at risk     37/554 (6.68%)     22/548 (4.01%)  
Myalgia † 1    
# participants affected / at risk     35/554 (6.32%)     41/548 (7.48%)  
Flank pain † 1    
# participants affected / at risk     14/554 (2.53%)     30/548 (5.47%)  
Nervous system disorders      
Dysgeusia † 1    
# participants affected / at risk     144/554 (25.99%)     198/548 (36.13%)  
Headache † 1    
# participants affected / at risk     124/554 (22.38%)     122/548 (22.26%)  
Dizziness † 1    
# participants affected / at risk     70/554 (12.64%)     82/548 (14.96%)  
Psychiatric disorders      
Insomnia † 1    
# participants affected / at risk     59/554 (10.65%)     61/548 (11.13%)  
Renal and urinary disorders      
Proteinuria † 1    
# participants affected / at risk     99/554 (17.87%)     76/548 (13.87%)  
Hematuria † 1    
# participants affected / at risk     24/554 (4.33%)     28/548 (5.11%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     86/554 (15.52%)     104/548 (18.98%)  
Dyspnoea † 1    
# participants affected / at risk     77/554 (13.90%)     92/548 (16.79%)  
Epistaxis † 1    
# participants affected / at risk     49/554 (8.84%)     96/548 (17.52%)  
Dysphonia † 1    
# participants affected / at risk     42/554 (7.58%)     12/548 (2.19%)  
Oropharyngeal pain † 1    
# participants affected / at risk     39/554 (7.04%)     54/548 (9.85%)  
Skin and subcutaneous tissue disorders      
Hair colour changes † 1    
# participants affected / at risk     168/554 (30.32%)     53/548 (9.67%)  
Palmar-plantar erythrodysaesthesia syndrome † 1    
# participants affected / at risk     163/554 (29.42%)     275/548 (50.18%)  
Rash † 1    
# participants affected / at risk     96/554 (17.33%)     126/548 (22.99%)  
Alopecia † 1    
# participants affected / at risk     77/554 (13.90%)     45/548 (8.21%)  
Dry skin † 1    
# participants affected / at risk     44/554 (7.94%)     47/548 (8.58%)  
Skin hypopigmentation † 1    
# participants affected / at risk     27/554 (4.87%)     7/548 (1.28%)  
Pruritus † 1    
# participants affected / at risk     22/554 (3.97%)     44/548 (8.03%)  
Yellow skin † 1    
# participants affected / at risk     4/554 (0.72%)     83/548 (15.15%)  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     256/554 (46.21%)     222/548 (40.51%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  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
No text entered.


  More Information