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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00753688
• Collaborator: (none)
• Enrollment: 369
• Locations: 81
• Arms: 2
• Duration (Months): 50
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A randomized double blind phase III trial of Pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or following prior therapy

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Soft Tissue	Drug: PAZOPANIB; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 369 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double Blind Phase III Trial of Pazopanib Versus Placebo in Patients With Soft Tissue Sarcoma Whose Disease Has Progressed During or Following Prior Therapy
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: PLACEBO matching placebo 800 mg once daily orally	Drug: Placebo; matching placebo 800 mg once daily orally
Experimental: PAZOPANIB 800 mg once daily orally	Drug: PAZOPANIB; 800 mg once daily orally

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [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)]

   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. The diagnosis of progression was based on tumor measurements, according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria, by independent radiologic assessment. The Kaplan-Meier method was used for PFS estimates.

Secondary Outcome Measures

1. Overall Survival (OS) [From the date of randomization until 215 deaths (assessed for an average of 12 months)]

   OS was defined as the time from the date of randomization to the date of death due to any cause. The length of this interval was calculated as the date of death minus the date of randomization plus 1 day. Participants who were alive at the time of analysis were censored at the date of last follow-up. The interim OS analysis was conducted when 215 (77 percent [%]) of the 279 required death events had occurred in the study. The Kaplan-Meier method was used for OS estimates.

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

   Overall response is defined as the number of participants who had a complete response (CR) or a partial response (PR). According to RECIST, Version 1.0: CR, disappearance of all lesions; PR, a >=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a >=20% increase in the sum of the LD of TLs, or the appearance of >=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of >=1 non-TL. Participants with no follow-up radiological disease assessment were categorized as not evaluable (NE).

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

   Time to response was defined as the time from the date of randomization until the date of first documented evidence of CR or PR (whichever status was recorded first). The Kaplan-Meier method was used for time to response estimates.

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

   Duration of response was defined as the time from the date of the first documented evidence of CR or PR until the date of either the first documented sign of PD or death due to any cause. Participants who neither died nor progressed were censored at the date of the last adequate radiologic assessment. The Kaplan-Meier method was used for duration of response estimates.

5. PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS) [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)]

   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.

6. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [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]

   Change from baseline in on-therapy SBP and DBP was calculated as the values at the indicated time points (Day 8 and 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) minus the value at baseline.

7. Change From Baseline in Heart Rate [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]

   Change from baseline in on-therapy heart rate was calculated as the value at the indicated time points (Day 8 and 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) minus the value at baseline.

8. 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 [From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)]

   Shifts in hematology values by grade were summarized based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE Version 3.0). Grade refers to the severity of the AE. The CTCAE Version 3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 (severe AE) and 4 (life-threatening or disabling AE) at any point in the study after baseline are reported.

9. 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 [From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)]

   Shifts in clinical chemistry values by grade were summarized based on the NCI CTCAE Version 3.0. Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 and 4 at any point in the study after baseline are reported. alkaline phosphatase, ALKP; alanine aminotransferase, ALT; aspartate aminotransferase, AST. Hyper/hypoglycemia refers to high/low glucose; hyper/hypokalemia refers to high/low potassium; hyper/hyponatremia refers to high/low sodium.

10. 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) [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)]

    LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function (based on the institutional lower limit of normal [LLN]). LVEF was assessed at BL, Week 12, and every second scheduled visit thereafter until study drug discontinuation and end of treatment or as clinically indicated by using multi-gated acquisition scan (MUGA) or echocardiogram (ECHO). Absolute change from BL was calculated as the on-study value minus the baseline value (LVEF is calculated as a percentage).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion/Exclusion Criteria:

• High or intermediate grade of soft tissue sarcoma; Low grade tumours allowed provided there is disease progression.

• Metastatic and measurable disease (RECIST);

• Subjects can have received maximum of 4 prior lines of systemic therapies (including up to 2 combination regimens) for advanced disease. (Neo) adjuvant/maintenance treatments are not counted for this criterion;

• Last dose of prior therapy can be given upto 14 days prior to start of study if all ongoing toxicity from prior anticancer therapy are grade 1 or resolved (except alopecia).

• Must have failed anthracycline-based therapy and available standard chemotherapies at the treating institution except if medically contraindicated or refused by patient;

• No treatment with anti-angiogenesis inhibitors;

• Age > 18 years

• WHO PS 0-1;

• No leptomeningeal or brain metastases, normal bone marrow, liver, renal and cardiac functions;

• No prior history of malignancies other than sarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix or breast or the patient has been free of any other malignancies for > 3 years)

• Adequate bone marrow function; adequate blood clotting results; adequate hepatic and renal function;

• No poorly controlled hypertension;

• Clinically normal cardiac function;

• No clinically significant gastrointestinal abnormalities including malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.

• No cerebrovascular accidents 1

• No transient ischemic attack, deep vein thrombosis or pulmonary embolism within past six months;

• No active bleeding or bleeding diathesis;

• No hemoptysis within six weeks of study drug;

• No major surgery or trauma within 28 days of therapy treatment;

• Concomitant medication restriction;

• No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib

• Ability to swallow & retain oral medication

• Adequate contraception must be used;

• No Psychological familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before randomization in the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35243
2	GSK Investigational Site	Los Angeles	California	United States	90048
3	GSK Investigational Site	Orange	California	United States	92868
4	GSK Investigational Site	Santa Monica	California	United States	90403
5	GSK Investigational Site	Chicago	Illinois	United States	60657
6	GSK Investigational Site	Boston	Massachusetts	United States	02114
7	GSK Investigational Site	Boston	Massachusetts	United States	02215
8	GSK Investigational Site	Minneapolis	Minnesota	United States	55455
9	GSK Investigational Site	Clevand	Ohio	United States	44106
10	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19106
11	GSK Investigational Site	Randwick	New South Wales	Australia	2031
12	GSK Investigational Site	Woolloongabba	Queensland	Australia	4102
13	GSK Investigational Site	Kurralta Park	South Australia	Australia	5037
14	GSK Investigational Site	Hobart	Tasmania	Australia	7000
15	GSK Investigational Site	Box Hill	Victoria	Australia	3128
16	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
17	GSK Investigational Site	Brussels		Belgium	1000
18	GSK Investigational Site	Brussels		Belgium	1200
19	GSK Investigational Site	Gent		Belgium	9000
20	GSK Investigational Site	Leuven		Belgium	3000
21	GSK Investigational Site	Liège		Belgium	4000
22	GSK Investigational Site	Herlev		Denmark	DK-2730
23	GSK Investigational Site	Bordeaux cedex		France	33076
24	GSK Investigational Site	Lille		France	59020
25	GSK Investigational Site	Lyon Cedex 08		France	69373
26	GSK Investigational Site	Marseille cedex 5		France	13385
27	GSK Investigational Site	Paris Cedex 5		France	75248
28	GSK Investigational Site	Saint-Priest en Jarez		France	42271
29	GSK Investigational Site	Vandoeuvre-Les-Nancy		France	54511
30	GSK Investigational Site	Villejuif		France	94805
31	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
32	GSK Investigational Site	Mannheim	Baden-Wuerttemberg	Germany	68167
33	GSK Investigational Site	Bad Saarow	Brandenburg	Germany	15526
34	GSK Investigational Site	Frankfurt	Hessen	Germany	60590
35	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
36	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
37	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50937
38	GSK Investigational Site	Dresden	Sachsen	Germany	01307
39	GSK Investigational Site	Napoli	Campania	Italy	80131
40	GSK Investigational Site	Roma	Lazio	Italy	00144
41	GSK Investigational Site	Milano	Lombardia	Italy	20133
42	GSK Investigational Site	Milano	Lombardia	Italy	20162
43	GSK Investigational Site	Rozzano (MI)	Lombardia	Italy	20089
44	GSK Investigational Site	Candiolo (TO)	Piemonte	Italy	10060
45	GSK Investigational Site	Torino	Piemonte	Italy	10153
46	GSK Investigational Site	Terni	Umbria	Italy	05100
47	GSK Investigational Site	Aichi		Japan	464-8681
48	GSK Investigational Site	Chiba		Japan	260-8717
49	GSK Investigational Site	Fukuoka		Japan	811-1395
50	GSK Investigational Site	Hokkaido		Japan	003-0804
51	GSK Investigational Site	Mie		Japan	514-8507
52	GSK Investigational Site	Okayama		Japan	700-8558
53	GSK Investigational Site	Osaka		Japan	537-8511
54	GSK Investigational Site	Osaka		Japan	540-0006
55	GSK Investigational Site	Tokyo		Japan	104-0045
56	GSK Investigational Site	Daegu		Korea, Republic of	705-717
57	GSK Investigational Site	Goyang-si, Gyeonggi-do		Korea, Republic of	410-769
58	GSK Investigational Site	Seoul		Korea, Republic of	110-744
59	GSK Investigational Site	Seoul		Korea, Republic of	120-752
60	GSK Investigational Site	Seoul		Korea, Republic of	135-710
61	GSK Investigational Site	Seoul		Korea, Republic of	138-736
62	GSK Investigational Site	Amsterdam		Netherlands	1066 CX
63	GSK Investigational Site	Groningen		Netherlands	9713 GZ
64	GSK Investigational Site	Leiden		Netherlands	2300 RC
65	GSK Investigational Site	Nijmegen		Netherlands	6525 GA
66	GSK Investigational Site	Rotterdam		Netherlands	3075 EA
67	GSK Investigational Site	Madrid		Spain	28040
68	GSK Investigational Site	Madrid		Spain	28041
69	GSK Investigational Site	Palma de Mallorca		Spain	07010
70	GSK Investigational Site	Valencia		Spain	46009
71	GSK Investigational Site	Göteborg		Sweden	SE413 45
72	GSK Investigational Site	Linköping		Sweden	SE-581 85
73	GSK Investigational Site	Lund		Sweden	SE-221 85
74	GSK Investigational Site	Umeå		Sweden	SE-901 85
75	GSK Investigational Site	Uppsala		Sweden	SE-751 85
76	GSK Investigational Site	Manchester	Lancashire	United Kingdom	M20 4BX
77	GSK Investigational Site	Glasgow		United Kingdom	G12 0YN
78	GSK Investigational Site	Leeds		United Kingdom	LS9 7TF
79	GSK Investigational Site	London		United Kingdom	SW3 6JJ
80	GSK Investigational Site	Nottingham		United Kingdom	NG5 1PB
81	GSK Investigational Site	Sheffield		United Kingdom	S10 2SJ

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. doi: 10.1016/S0140-6736(12)60651-5. Epub 2012 May 16.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00753688
• Other Study ID Numbers: VEG110727; NCT00794521
• First Posted: Sep 16, 2008
• Last Update Posted: Aug 22, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by GlaxoSmithKline: metastatic soft-tissue sarcoma; pazopanib; Soft Tissue Sarcoma; placebo
• Additional relevant MeSH terms: Sarcoma

Study Results

Participant Flow

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Period Title: Overall Study
STARTED	123	246
Ongoing - in Follow-up	15	31
COMPLETED	0	0
NOT COMPLETED	123	246

Baseline Characteristics

Arm/Group Title	Placebo	Pazopanib	Total
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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 of all reporting groups
Overall Participants	123	246	369
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.7 (13.77)	54.0 (14.92)	53.2 (14.57)
Sex: Female, Male (Count of Participants)
Female	69 56.1%	147 59.8%	216 58.5%
Male	54 43.9%	99 40.2%	153 41.5%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	2 1.6%	4 1.6%	6 1.6%
American Indian or Alaska Native	0 0%	1 0.4%	1 0.3%
Asian - Central/South Asian Heritage	2 1.6%	0 0%	2 0.5%
Asian - East Asian Heritage	7 5.7%	24 9.8%	31 8.4%
Asian - Japanese Heritage	16 13%	31 12.6%	47 12.7%
Asian - South East Asian Heritage	2 1.6%	2 0.8%	4 1.1%
White - Arabic/North African Heritage	2 1.6%	1 0.4%	3 0.8%
White - White/Caucasian/European Heritage	89 72.4%	174 70.7%	263 71.3%
Mixed Race	1 0.8%	0 0%	1 0.3%
Unknown	2 1.6%	9 3.7%	11 3%
Number of participants in the indicated soft tissue sarcoma (STS) subgroups at Baseline (participants) [Number]
Leiomyosarcoma	49 39.8%	109 44.3%	158 42.8%
Synovial sarcoma	13 10.6%	25 10.2%	38 10.3%
Other STS histologies	61 49.6%	112 45.5%	173 46.9%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
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. The diagnosis of progression was based on tumor measurements, according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria, by independent radiologic assessment. The Kaplan-Meier method was used for PFS estimates.
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)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants analyzed in the treatment arm they were allocated by randomization.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	123	246
Median (95% Confidence Interval) [weeks]	7.0	20.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Stratified two-sided log rank p-value
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	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+).

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of randomization to the date of death due to any cause. The length of this interval was calculated as the date of death minus the date of randomization plus 1 day. Participants who were alive at the time of analysis were censored at the date of last follow-up. The interim OS analysis was conducted when 215 (77 percent [%]) of the 279 required death events had occurred in the study. The Kaplan-Meier method was used for OS estimates.
Time Frame	From the date of randomization until 215 deaths (assessed for an average of 12 months)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	123	246
Median (95% Confidence Interval) [months]	10.7	12.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.256
	Comments	Stratified two-sided log rank p-value
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	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+).

3. Secondary Outcome

Title	Number of Participants in the Indicated Categories for Overall Response Assessed by an Independent Radiologist and the Investigator
Description	Overall response is defined as the number of participants who had a complete response (CR) or a partial response (PR). According to RECIST, Version 1.0: CR, disappearance of all lesions; PR, a >=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a >=20% increase in the sum of the LD of TLs, or the appearance of >=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of >=1 non-TL. Participants with no follow-up radiological disease assessment were categorized as not evaluable (NE).
Time Frame	From the start of treatment until disease progression (assessed for an average of 10 months)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	123	246
CR, Independent radiologist assessed	0 0%	0 0%
PR, Independent radiologist assessed	0 0%	11 4.5%
SD, Independent radiologist assessed	33 26.8%	134 54.5%
PD, Independent radiologist assessed	76 61.8%	66 26.8%
NE, Independent radiologist assessed	14 11.4%	35 14.2%
CR, Investigator assessed	0 0%	0 0%
PR, Investigator assessed	0 0%	23 9.3%
SD, Investigator assessed	36 29.3%	138 56.1%
PD, Investigator assessed	83 67.5%	70 28.5%
NE, Investigator assessed	4 3.3%	15 6.1%

4. Secondary Outcome

Title	Time to Response Assessed by an Independent Radiologist and the Investigator
Description	Time to response was defined as the time from the date of randomization until the date of first documented evidence of CR or PR (whichever status was recorded first). The Kaplan-Meier method was used for time to response estimates.
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)

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants who achieved a confirmed CR or PR, as determined independently by the Independent Radiologist and the Investigator, were analyzed. Only results for the pazopanib arm are given because there was no response in the placebo arm.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	0	23
Independent radiologist assessed, n=0, 11	8.4
Investigator assessed, n=0, 23	8.1

5. Secondary Outcome

Title	Duration of Response Assessed by the Independent Radiologist and the Investigator
Description	Duration of response was defined as the time from the date of the first documented evidence of CR or PR until the date of either the first documented sign of PD or death due to any cause. Participants who neither died nor progressed were censored at the date of the last adequate radiologic assessment. The Kaplan-Meier method was used for duration of response estimates.
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)

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants who achieved a confirmed CR or PR, as determined independently by the Independent Radiologist and the Investigator, were analyzed. Only results for the pazopanib arm are given because there was no response in the placebo arm.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	0	23
Independent radiologist assessed, n=0, 11	38.9
Investigator assessed, n=0, 23	32.1

6. Secondary Outcome

Title	PFS in the Indicated Histology Subgroups of Soft Tissue Sarcoma (STS)
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)

Outcome Measure Data

Analysis Population Description

ITT Population. The "n"s in the category titles represent the number of participants in each treatment arm with the indicated STS.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	123	246
Leiomyosarcoma, n=49, 109	8.1	20.1
Synovial sarcoma, n=13, 25	4.1	17.9
Other STS, n=61, 112	4.3	20.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Stratified two-sided log rank p-value for leiomyosarcoma
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Stratified two-sided log rank p-value for synovial sarcoma
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; 0.19 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Stratified two-sided log rank p-value for other STS histologies
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	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 Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description	Change from baseline in on-therapy SBP and DBP was calculated as the values at the indicated time points (Day 8 and 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) minus the value at baseline.
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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who had started their allocated treatment (at least one dose of the study drug). Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	120	235
SBP, Day 8, n=120, 235	-0.6 (13.37)	10.3 (15.96)
SBP, Week 4, n=106, 224	-0.2 (12.83)	10.9 (19.47)
SBP, Week 8, n=71, 180	0.0 (13.60)	7.2 (17.46)
SBP, Week 12, n=31, 115	-3.1 (15.82)	4.9 (18.21)
SBP, Week 16, n=35, 136	-0.6 (15.91)	4.9 (18.49)
SBP, Week 20, n=14, 66	-2.6 (14.89)	3.9 (19.84)
SBP, Week 24, n=22, 107	-3.8 (16.71)	2.7 (20.24)
SBP, Week 28, n=9, 41	0.2 (22.82)	0.9 (15.70)
SBP, Week 32, n=12, 76	2.8 (12.50)	3.2 (18.89)
SBP, Week 36, n=5, 24	3.6 (10.71)	1.9 (17.71)
SBP, Week 40, n=5, 62	6.8 (15.47)	3.2 (19.75)
SBP, Week 44, n=3, 16	6.0 (19.31)	1.2 (19.45)
SBP, Week 48, n=3, 37	-1.7 (14.05)	-1.7 (16.90)
SBP, Week 52, n=1, 6	-4.0 (0)	9.8 (18.28)
SBP, Week 56, n=1, 27	16.0 (0)	1.4 (20.86)
SBP, Week 60, n=0, 6	0 (0)	7.0 (18.60)
SBP, Week 64, n=1, 15	20.0 (0)	-3.0 (19.26)
SBP, Week 68, n=0, 2	0 (0)	14.5 (3.54)
SBP, Week 72, n=1, 9	8.0 (0)	-1.1 (15.83)
SBP, Week 76, n=0, 1	0 (0)	16.0 (0)
SBP, Week 80, n=1, 5	19.0 (0)	-0.9 (22.66)
SBP, Week 88, n=1, 3	3.0 (0)	3.9 (22.90)
SBP, Week 96, n=1, 2	13.0 (0)	-3.0 (14.14)
SBP, Week 104, n=1, 1	18.0 (0)	6.0 (0)
DBP, Day 8, n=120, 235	-0.2 (9.53)	7.2 (10.68)
DBP, Week 4, n=106, 224	-0.2 (9.51)	8.2 (11.37)
DBP, Week 8, n=71, 180	-0.3 (9.24)	6.6 (12.18)
DBP, Week 12, n=31, 115	-0.1 (10.81)	3.9 (11.31)
DBP, Week 16, n=35, 136	0.8 (10.46)	5.3 (12.12)
DBP, Week 20, n=14, 66	-0.3 (8.61)	4.5 (12.22)
DBP, Week 24, n=22, 107	-1.6 (11.78)	3.7 (14.44)
DBP, Week 28, n=9, 41	-1.9 (12.33)	3.7 (11.28)
DBP, Week 32, n=12, 76	-2.0 (7.30)	3.9 (11.59)
DBP, Week 36, n=5, 24	-6.6 (9.63)	4.1 (13.28)
DBP, Week 40, n=5, 62	3.4 (9.24)	2.9 (13.34)
DBP, Week 44, n=3, 16	4.7 (5.03)	1.7 (12.48)
DBP, Week 48, n=3, 37	2.0 (4.36)	3.7 (12.01)
DBP, Week 52, n=1, 6	1.0 (0)	12.0 (15.06)
DBP, Week 56, n=1, 27	12.0 (0)	4.4 (12.28)
DBP, Week 60, n=0, 6	0 (0)	12.7 (14.39)
DBP, Week 64, n=1, 15	10.0 (0)	-2.2 (14.21)
DBP, Week 68, n=0, 2	0 (0)	17.0 (25.46)
DBP, Week 72, n=1, 9	13.0 (0)	0.8 (12.88)
DBP, Week 76, n=0, 1	0 (0)	4.0 (0)
DBP, Week 80, n=1, 5	14.0 (0)	-3.3 (15.15)
DBP, Week 88, n=1, 3	9.0 (0)	5.2 (3.87)
DBP, Week 96, n=1, 2	6.0 (0)	7.0 (5.66)
DBP, Week 104, n=1, 1	12.0 (0)	12.0 (0)

8. Secondary Outcome

Title	Change From Baseline in Heart Rate
Description	Change from baseline in on-therapy heart rate was calculated as the value at the indicated time points (Day 8 and 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) minus the value at baseline.
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

Outcome Measure Data

Analysis Population Description

Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	113	225
Day 8, n=113, 225	1.6 (12.61)	-4.4 (11.24)
Week 4, n=98, 208	3.1 (13.06)	-2.7 (13.51)
Week 8, n=66, 171	2.1 (15.03)	-1.6 (14.31)
Week 12, n=29, 103	1.1 (17.32)	-2.4 (11.67)
Week 16, n=31, 127	6.0 (16.78)	-3.7 (12.76)
Week 20, n=12, 57	0.6 (22.95)	-3.4 (11.71)
Week 24, n=21, 94	4.5 (18.14)	-5.0 (12.83)
Week 28, n=7, 37	-1.1 (27.99)	-3.8 (13.68)
Week 32, n=12, 72	-1.7 (18.38)	-2.7 (12.63)
Week 36, n=5, 24	-11.8 (32.57)	0.9 (13.37)
Week 40, n=5, 58	-8.2 (30.19)	-2.4 (12.84)
Week 44, n=3, 15	7.0 (16.09)	-0.9 (14.02)
Week 48, n=3, 33	9.0 (18.00)	1.9 (14.38)
Week 52, n=1, 5	-8.0 (0)	-3.4 (16.96)
Week 56, n=1, 24	31.0 (0)	-0.4 (15.14)
Week 60, n=0, 6	0 (0)	4.3 (15.13)
Week 64, n=1, 13	36.0 (0)	-1.5 (13.56)
Week 68, n=0, 2	0 (0)	9.5 (0.71)
Week 72, n=1, 8	14.0 (0)	2.6 (12.60)
Week 76, n=0, 1	0 (0)	5.0 (0)
Week 80, n=1, 5	24.0 (0)	2.8 (16.08)
Week 88, n=1, 3	9.0 (0)	-3.0 (10.58)
Week 96, n=1, 2	17.0 (0)	-5.0 (4.24)
Week 104, n=1, 1	30.0 (0)	1.0 (0)

9. Secondary Outcome

Title	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
Description	Shifts in hematology values by grade were summarized based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE Version 3.0). Grade refers to the severity of the AE. The CTCAE Version 3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 (severe AE) and 4 (life-threatening or disabling AE) at any point in the study after baseline are reported.
Time Frame	From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	123	239
Hemoglobin, Any Increase, n=123, 239	28 22.8%	65 26.4%
Hemoglobin, Increase to Grade 3, n=123, 239	1 0.8%	11 4.5%
Hemoglobin, Increase to Grade 4, n=123, 239	1 0.8%	4 1.6%
Lymphocytes, Any Increase, n=123, 238	44 35.8%	102 41.5%
Lymphocytes, Increase to Grade 3, n=123, 238	11 8.9%	23 9.3%
Lymphocytes, Increase to Grade 4, n=123, 238	2 1.6%	0 0%
Neutrophils, Any Increase, n=123, 239	8 6.5%	79 32.1%
Neutrophils, Increase to Grade 3, n=123, 239	0 0%	10 4.1%
Neutrophils, Increase to Grade 4, n=123, 239	0 0%	0 0%
Platelets, Any Increase, n=123, 239	7 5.7%	86 35%
Platelets, Increase to Grade 3, n=123, 239	0 0%	7 2.8%
Platelets, Increase to Grade 4, n=123, 239	0 0%	2 0.8%
White Blood Cells, Any Increase, n=123, 239	18 14.6%	106 43.1%
White Blood Cells, Increase to Grade 3, n=123, 239	0 0%	3 1.2%
White Blood Cells, Increase to Grade , n=123, 239	0 0%	0 0%

10. Secondary Outcome

Title	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
Description	Shifts in clinical chemistry values by grade were summarized based on the NCI CTCAE Version 3.0. Participants with a missing baseline grade were assumed to have a baseline Grade of 0. Any increase in grade from baseline and shifts to Grade 3 and 4 at any point in the study after baseline are reported. alkaline phosphatase, ALKP; alanine aminotransferase, ALT; aspartate aminotransferase, AST. Hyper/hypoglycemia refers to high/low glucose; hyper/hypokalemia refers to high/low potassium; hyper/hyponatremia refers to high/low sodium.
Time Frame	From baseline (Day 1) until study drug discontinuation or end of treatment (assessed for an average of 20 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	123	239
ALKP, Any Increase, n=123, 237	28 22.8%	77 31.3%
ALKP, Increase to Grade 3, n=123, 237	1 0.8%	7 2.8%
ALKP, Increase to Grade 4, n=123, 237	0 0%	0 0%
ALT, Any Increase, n=123, 237	22 17.9%	110 44.7%
ALT, Increase to Grade 3, n=123, 237	3 2.4%	18 7.3%
ALT, Increase to Grade 4, n=123, 237	1 0.8%	5 2%
AST, Any Increase, n=123, 239	27 22%	122 49.6%
AST, Increase to Grade 3, n=123, 239	2 1.6%	13 5.3%
AST, Increase to Grade 4, n=123, 239	0 0%	6 2.4%
Albumin, Any Increase, n=123, 239	26 21.1%	81 32.9%
Albumin, Increase to Grade 3, n=123, 239	0 0%	2 0.8%
Albumin, Increase to Grade 4, n=123, 239	0 0%	0 0%
Creatinine, Any Increase, n=123, 239	9 7.3%	28 11.4%
Creatinine, Increase to Grade 3, n=123, 239	0 0%	1 0.4%
Creatinine, Increase to Grade 4, n=123, 239	0 0%	0 0%
Hyperglycemia, Any Increase, n=122, 238	43 35%	106 43.1%
Hyperglycemia, Increase to Grade 3, n=122, 238	2 1.6%	1 0.4%
Hyperglycemia, Increase to Grade 4, n=122, 238	0 0%	0 0%
Hyperkalemia, Any Increase, n=123, 238	13 10.6%	37 15%
Hyperkalemia, Increase to Grade 3, n=123, 238	0 0%	3 1.2%
Hyperkalemia, Increase to Grade 4, n=123, 238	0 0%	0 0%
Hypernatremia, Any Increase, n=123, 238	3 2.4%	10 4.1%
Hypernatremia, Increase to Grade 3, n=123, 238	0 0%	0 0%
Hypernatremia, Increase to Grade 4, n=123, 238	0 0%	0 0%
Hypoglycemia, Any Increase, n=122, 238	4 3.3%	21 8.5%
Hypoglycemia, Increase to Grade 3, n=122, 238	0 0%	1 0.4%
Hypoglycemia, Increase to Grade 4, n=122, 238	0 0%	0 0%
Hypokalemia, Any Increase, n=123, 238	11 8.9%	32 13%
Hypokalemia, Increase to Grade 3, n=123, 238	1 0.8%	6 2.4%
Hypokalemia, Increase to Grade 4, n=123, 238	0 0%	1 0.4%
Hyponatremia, Any Increase, n=123, 238	25 20.3%	74 30.1%
Hyponatremia, Increase to Grade 3, n=123, 238	4 3.3%	9 3.7%
Hyponatremia, Increase to Grade 4, n=123, 238	0 0%	0 0%
Total Bilirubin, Any Increase, n=122, 237	9 7.3%	68 27.6%
Total Bilirubin, Increase to Grade 3, n=122, 237	2 1.6%	3 1.2%
Total Bilirubin, Increase to Grade 4, n=122, 237	0 0%	0 0%

11. Secondary Outcome

Title	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)
Description	LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function (based on the institutional lower limit of normal [LLN]). LVEF was assessed at BL, Week 12, and every second scheduled visit thereafter until study drug discontinuation and end of treatment or as clinically indicated by using multi-gated acquisition scan (MUGA) or echocardiogram (ECHO). Absolute change from BL was calculated as the on-study value minus the baseline value (LVEF is calculated as a percentage).
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)

Outcome Measure Data

Analysis Population Description

Safety Population. Data were analyzed for participants who were on-therapy and provided data at the indicated time point.

Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent	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
Measure Participants	39	140
Any Increase	15 12.2%	39 15.9%
No Change	6 4.9%	14 5.7%
0 to <10% Decrease	15 12.2%	66 26.8%
10 to 19% Decrease	3 2.4%	15 6.1%
>=20% Decrease	0 0%	6 2.4%
>=10% Decrease and >= LLN	3 2.4%	8 3.3%
>=10% Decrease and below LLN	0 0%	13 5.3%
>=20% Decrease and >= LLN	0 0%	1 0.4%
>=20% Decrease and below LLN	0 0%	5 2%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from Baseline through End of Study (average of 20 study weeks).
Adverse Event Reporting 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.
Arm/Group Title	Placebo		Pazopanib
Arm/Group Description	Matching placebo tablets administered orally once daily for a duration until participants experienced disease progression, death, unacceptable toxicity, or participants withdrew consent		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
All Cause Mortality
	Placebo		Pazopanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Pazopanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/123 (23.6%)		99/240 (41.3%)
Blood and lymphatic system disorders
Febrile neutropenia	0/123 (0%)		2/240 (0.8%)
Thrombotic microangiopathy	0/123 (0%)		1/240 (0.4%)
Cardiac disorders
Left ventricular dysfunction	0/123 (0%)		5/240 (2.1%)
Atrial fibrillation	1/123 (0.8%)		1/240 (0.4%)
Atrial flutter	1/123 (0.8%)		0/240 (0%)
Cardio-respiratory arrest	0/123 (0%)		1/240 (0.4%)
Myocardial infarction	0/123 (0%)		1/240 (0.4%)
Pericardial effusion	0/123 (0%)		1/240 (0.4%)
Sinus bradycardia	1/123 (0.8%)		0/240 (0%)
Gastrointestinal disorders
Gastrointestinal pain	2/123 (1.6%)		4/240 (1.7%)
Vomiting	1/123 (0.8%)		4/240 (1.7%)
Colonic obstruction	1/123 (0.8%)		1/240 (0.4%)
Nausea	1/123 (0.8%)		1/240 (0.4%)
Small intestinal obstruction	0/123 (0%)		2/240 (0.8%)
Constipation	1/123 (0.8%)		0/240 (0%)
Diarrhea	0/123 (0%)		1/240 (0.4%)
Duodenal ulcer	0/123 (0%)		1/240 (0.4%)
Enterocutaneous fistula	0/123 (0%)		1/240 (0.4%)
Gastric stenosis	0/123 (0%)		1/240 (0.4%)
Gastrointestinal fistula	0/123 (0%)		1/240 (0.4%)
Hematemesis	1/123 (0.8%)		0/240 (0%)
Ileus	1/123 (0.8%)		0/240 (0%)
Peritoneal hemorrhage	0/123 (0%)		1/240 (0.4%)
Upper gastrointestinal hemorrhage	0/123 (0%)		1/240 (0.4%)
Oesophageal haemorrhage	0/123 (0%)		1/240 (0.4%)
Oesophageal stenosis	0/123 (0%)		1/240 (0.4%)
General disorders
Fatigue	1/123 (0.8%)		5/240 (2.1%)
Chest pain	0/123 (0%)		4/240 (1.7%)
Pyrexia	3/123 (2.4%)		1/240 (0.4%)
Performance status decreased	0/123 (0%)		3/240 (1.3%)
Disease progression	1/123 (0.8%)		1/240 (0.4%)
Asthenia	0/123 (0%)		1/240 (0.4%)
Death	0/123 (0%)		1/240 (0.4%)
Localized edema	1/123 (0.8%)		0/240 (0%)
Multi-organ failure	0/123 (0%)		1/240 (0.4%)
Mass	0/123 (0%)		1/240 (0.4%)
Immune system disorders
Hypersensitivity	0/123 (0%)		1/240 (0.4%)
Infections and infestations
Pneumonia	0/123 (0%)		4/240 (1.7%)
Sepsis	1/123 (0.8%)		2/240 (0.8%)
Abscess	0/123 (0%)		1/240 (0.4%)
Biliary tract infection	0/123 (0%)		1/240 (0.4%)
Candida sepsis	0/123 (0%)		1/240 (0.4%)
Clostridial infection	0/123 (0%)		1/240 (0.4%)
Cystitis	0/123 (0%)		1/240 (0.4%)
Device related infection	0/123 (0%)		1/240 (0.4%)
Diverticulitis	0/123 (0%)		1/240 (0.4%)
Gastroenteritis	0/123 (0%)		1/240 (0.4%)
Infection	0/123 (0%)		1/240 (0.4%)
Infective tenosynovitis	0/123 (0%)		1/240 (0.4%)
Lactobacillus infection	0/123 (0%)		1/240 (0.4%)
Lung infection	0/123 (0%)		1/240 (0.4%)
Pelvic abscess	0/123 (0%)		1/240 (0.4%)
Pyelonephritis	1/123 (0.8%)		0/240 (0%)
Skin infection	0/123 (0%)		1/240 (0.4%)
Streptococcal sepsis	0/123 (0%)		1/240 (0.4%)
Superinfection bacterial	0/123 (0%)		1/240 (0.4%)
Tooth abscess	0/123 (0%)		1/240 (0.4%)
Wound infection	0/123 (0%)		1/240 (0.4%)
Wound infection pseudomonas	0/123 (0%)		1/240 (0.4%)
Bacterial sepsis	0/123 (0%)		1/240 (0.4%)
Injury, poisoning and procedural complications
Femur fracture	0/123 (0%)		1/240 (0.4%)
Radiation injury	0/123 (0%)		1/240 (0.4%)
Radiation skin injury	0/123 (0%)		1/240 (0.4%)
Vascular graft thrombosis	0/123 (0%)		1/240 (0.4%)
Investigations
Alanine aminotransferase increased	1/123 (0.8%)		9/240 (3.8%)
Hemoglobin decreased	2/123 (1.6%)		8/240 (3.3%)
Aspartate aminotransferase increased	0/123 (0%)		6/240 (2.5%)
Gamma-glutamyltransferase increased	0/123 (0%)		6/240 (2.5%)
Platelet count decreased	1/123 (0.8%)		3/240 (1.3%)
Blood bilirubin increased	1/123 (0.8%)		2/240 (0.8%)
Neutrophil percentage	1/123 (0.8%)		2/240 (0.8%)
Alanine aminotransferase	1/123 (0.8%)		1/240 (0.4%)
Aspartate aminotransferase	0/123 (0%)		2/240 (0.8%)
Blood potassium decreased	1/123 (0.8%)		1/240 (0.4%)
Lymphocyte percentage	2/123 (1.6%)		0/240 (0%)
Neutrophil count decreased	0/123 (0%)		2/240 (0.8%)
Bilirubin conjugated	0/123 (0%)		1/240 (0.4%)
Blood alkaline phosphatase increased	0/123 (0%)		1/240 (0.4%)
Blood cholesterol abnormal	0/123 (0%)		1/240 (0.4%)
Blood lactate dehydrogenase increased	0/123 (0%)		1/240 (0.4%)
Hemoglobin	0/123 (0%)		1/240 (0.4%)
Neutrophil percentage decreased	0/123 (0%)		1/240 (0.4%)
Urine protein/creatinine ratio	0/123 (0%)		1/240 (0.4%)
White blood cell count decreased	0/123 (0%)		2/240 (0.8%)
Metabolism and nutrition disorders
Decreased appetite	0/123 (0%)		1/240 (0.4%)
Dehydration	0/123 (0%)		2/240 (0.8%)
Hypercalcemia	1/123 (0.8%)		1/240 (0.4%)
Hypoglycemia	0/123 (0%)		1/240 (0.4%)
Lactic acidosis	0/123 (0%)		1/240 (0.4%)
Musculoskeletal and connective tissue disorders
Myalgia	1/123 (0.8%)		2/240 (0.8%)
Musculoskeletal chest pain	0/123 (0%)		1/240 (0.4%)
Musculoskeletal pain	0/123 (0%)		1/240 (0.4%)
Rhabdomyolysis	0/123 (0%)		1/240 (0.4%)
Tendonitis	0/123 (0%)		1/240 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	3/123 (2.4%)		4/240 (1.7%)
Malignant pleural effusion	1/123 (0.8%)		2/240 (0.8%)
Leiomyosarcoma metastatic	0/123 (0%)		1/240 (0.4%)
Metastases to skin	0/123 (0%)		1/240 (0.4%)
Neoplasm	0/123 (0%)		1/240 (0.4%)
Nervous system disorders
Peripheral sensory neuropathy	1/123 (0.8%)		1/240 (0.4%)
Cerebral infarction	0/123 (0%)		1/240 (0.4%)
Hemorrhage intracranial	0/123 (0%)		1/240 (0.4%)
Headache	0/123 (0%)		1/240 (0.4%)
Peripheral motor neuropathy	1/123 (0.8%)		0/240 (0%)
Subarachnoid hemorrhage	0/123 (0%)		1/240 (0.4%)
Syncope	0/123 (0%)		1/240 (0.4%)
Psychiatric disorders
Confusional state	0/123 (0%)		1/240 (0.4%)
Depressed mood	0/123 (0%)		1/240 (0.4%)
Renal and urinary disorders
Renal failure	0/123 (0%)		2/240 (0.8%)
Hematuria	0/123 (0%)		1/240 (0.4%)
Nephrolithiasis	1/123 (0.8%)		0/240 (0%)
Nephrotic syndrome	0/123 (0%)		1/240 (0.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/123 (2.4%)		9/240 (3.8%)
Pneumothorax	0/123 (0%)		6/240 (2.5%)
Pleural effusion	1/123 (0.8%)		4/240 (1.7%)
Lung disorder	0/123 (0%)		2/240 (0.8%)
Respiratory failure	2/123 (1.6%)		0/240 (0%)
Acute respiratory distress syndrome	1/123 (0.8%)		0/240 (0%)
Hemoptysis	1/123 (0.8%)		0/240 (0%)
Pulmonary hemorrhage	1/123 (0.8%)		0/240 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/123 (0%)		1/240 (0.4%)
Vascular disorders
Embolism arterial	2/123 (1.6%)		6/240 (2.5%)
Hemorrhage	0/123 (0%)		1/240 (0.4%)
Ischemia	0/123 (0%)		1/240 (0.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Pazopanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/123 (87.8%)		232/240 (96.7%)
Cardiac disorders
Left ventricular dysfunction	5/123 (4.1%)		19/240 (7.9%)
Endocrine disorders
Hypothyroidism	0/123 (0%)		20/240 (8.3%)
Eye disorders
Vision blurred	2/123 (1.6%)		12/240 (5%)
Gastrointestinal disorders
Nausea	27/123 (22%)		135/240 (56.3%)
Diarrhea	19/123 (15.4%)		141/240 (58.8%)
Vomiting	14/123 (11.4%)		81/240 (33.8%)
Gastrointestinal pain	11/123 (8.9%)		57/240 (23.8%)
Constipation	21/123 (17.1%)		39/240 (16.3%)
Stomatitis	4/123 (3.3%)		27/240 (11.3%)
Abdominal pain upper	7/123 (5.7%)		19/240 (7.9%)
Dry mouth	6/123 (4.9%)		16/240 (6.7%)
Dyspepsia	2/123 (1.6%)		18/240 (7.5%)
General disorders
Fatigue	59/123 (48%)		157/240 (65.4%)
Edema peripheral	11/123 (8.9%)		33/240 (13.8%)
Pyrexia	12/123 (9.8%)		25/240 (10.4%)
Chest pain	7/123 (5.7%)		26/240 (10.8%)
Chills	1/123 (0.8%)		14/240 (5.8%)
Infections and infestations
Nasopharyngitis	7/123 (5.7%)		13/240 (5.4%)
Investigations
Weight decreased	9/123 (7.3%)		122/240 (50.8%)
Ear, nose and throat examination abnormal	3/123 (2.4%)		29/240 (12.1%)
Weight increased	9/123 (7.3%)		12/240 (5%)
Metabolism and nutrition disorders
Decreased appetite	23/123 (18.7%)		97/240 (40.4%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	24/123 (19.5%)		56/240 (23.3%)
Myalgia	11/123 (8.9%)		56/240 (23.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	26/123 (21.1%)		71/240 (29.6%)
Nervous system disorders
Dysgeusia	4/123 (3.3%)		66/240 (27.5%)
Headache	10/123 (8.1%)		57/240 (23.8%)
Dizziness	5/123 (4.1%)		26/240 (10.8%)
Peripheral sensory neuropathy	10/123 (8.1%)		22/240 (9.2%)
Psychiatric disorders
Insomnia	7/123 (5.7%)		24/240 (10%)
Anxiety	8/123 (6.5%)		20/240 (8.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	21/123 (17.1%)		49/240 (20.4%)
Cough	15/123 (12.2%)		43/240 (17.9%)
Dysphonia	3/123 (2.4%)		18/240 (7.5%)
Epistaxis	2/123 (1.6%)		19/240 (7.9%)
Skin and subcutaneous tissue disorders
Hair color changes	3/123 (2.4%)		93/240 (38.8%)
Exfoliative rash	11/123 (8.9%)		46/240 (19.2%)
Alopecia	1/123 (0.8%)		29/240 (12.1%)
Skin disorder	1/123 (0.8%)		28/240 (11.7%)
Skin hypopigmentation	0/123 (0%)		28/240 (11.7%)
Dry skin	1/123 (0.8%)		16/240 (6.7%)
Vascular disorders
Hypertension	7/123 (5.7%)		101/240 (42.1%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.