Safety and Efficacy of GW786034 (Pazopanib) In Metastatic Renal Cell Carcinoma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00334282
• Collaborator: (none)
• Enrollment: 435
• Locations: 100
• Arms: 2
• Duration (Months): 104
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To evaluate efficacy and safety of pazopanib compared to placebo in patients with locally advanced and/ or metastatic renal cell carcinoma (RCC). Approximately 350-400 eligible patients will be stratified and randomized in a 2:1 ratio to receive either 800 mg pazopanib once daily or matching placebo. The study treatment will continue until patients experience disease progression, unacceptable toxicity or death. Primary objective of the study is to evaluate and compare the two treatment arms for progression-free survival. Principal secondary objective is to evaluate and compare the two treatment arms with respect to overall survival. Other objectives are overall response rate [complete response (CR) + partial response (PR)], rate of CR + PR + 6 months stable disease, and the incidence, severity and causality of adverse events and serious adverse events. Safety and efficacy assessments will be regularly performed on all patients. An Independent Data Monitoring Committee will be established to monitor safety during the course of the study and to evaluate interim efficacy data on overall survival.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: Pazopanib; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 435 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo Controlled, Multi-center Phase III Study to Evaluate the Efficacy and Safety of Pazopanib (GW786034) Compared to Placebo in Patients With Locally Advanced and/or Metastatic Renal Cell Carcinoma
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo arm matching placebo (800 mg tablet) once daily	Drug: placebo; matching placebo (800 mg tablet) once daily
Experimental: pazopanib arm Oral pazopanib tablet 800 mg once daily continuously	Drug: Pazopanib; Oral pazopanib tablet 800 mg once daily continuously; Other Names: votrient

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Randomization until progression (up to 2 years)]

   Progression-free survival (PFS) is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause. Assessments of progression and non-progression were made by an independent imaging review committee (IRC) for the primary analysis.

Secondary Outcome Measures

1. Overall Survival [Randomization until death (up to 2 years)]

   Overall survival is defined as the time from randomization until death. The length of this interval was estimated as the date of death minus the date of randomization plus 1 day. Participants who were still alive at the time of analysis were censored.

2. Overall Response [Baseline until either response or progression (up to 2 years)]

   Overall response is the number of participants who had a complete response (CR) or a partial response (PR). Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the Baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease, small changes that do not meet previously given criteria. IRC, independent review committee.

3. Participants With Complete Response, Partial Response, or 6 Months of Stable Disease [Baseline until 6 months post-Baseline or progressive disease]

   This is similar to overall response rate, but also includes participants who had stable disease for at least 6 months. Per Response Evaluation Criteria In Solid Tumors (RECIST): CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the Baseline sum; Stable Disease, small changes that do not meet previously given criteria; Progressive Disease, a >=20% increase in target lesions. IRC, independent review committee.

4. Duration of Response [Time from response until progression (up to 2 years)]

   Duration of response is defined as the time from first observation of response until progression of disease or death.

5. Time to Response as Assessed by an Independent Review Committee (IRC) and the Investigator [Randomization until CR or PR (assessed for up to 2 years)]

   Time to response is defined as the time from randomization until the first documented evidence of complete response (all detectable tumor has disappeared) or partial response (a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the Baseline sum) (whichever status was recorded first).

6. Adjusted Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 (EORTC QLQ C-30) Score at Weeks 6, 12, 18, 24, and 48 [Baseline and Weeks 6, 12, 18, 24, and 48]

   The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer participants. The analyses for EORTC QLQ-C30 were focused on global health status/Health-Related Quality of Life (HRQOL) scores on the questionnaire. The scores (from 1 [very poor quality of life] to 7 [excellent quality of life]) for these two questions were averaged and then transformed to a 0 - 100 scale (based on published methods) prior to analysis of change from Baseline.

7. Adjusted Mean Change From Baseline in the Index Score of the EQ-5D (EuroQoL [Quality of Life]-5D) Questionnaire at Weeks 6, 12, 18, 24, and 48 [Baseline and Weeks 6, 12, 18, 24, and 48]

   The EQ-5D is comprised of a 5-item health status measure and a visual analogue rating scale, and measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (no, moderate, and extreme problems). Scoring of the EQ-5D yields an index-based summary score (Index), through application of societal weights, and a VAS score (VAS). Index is interpreted on a continuum from 1.0 (best possible health) to 0 (represents dead), to some health sates being worse than dead (<0).

8. Adjusted Mean Change From Baseline in the Visual Analog Scale (VAS) Score of the EQ-5D (EuroQoL [Quality of Life]-5D) Questionnaire at Weeks 6, 12, 18, 24, and 48 [Baseline and Weeks 6, 12, 18, 24, and 48]

   The EQ-5D is comprised of a 5-item health status measure and a visual analogue rating scale, and measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (no, moderate, and extreme problems). Scoring of the EQ-5D yields an index-based summary score (Index) and a VAS score (VAS), obtained from participant's self-reports of their health on a VAS thermometer scale. The EQ-5D VAS ranges from 0% (worst imaginable health state) to 100% (best imaginable health state).

9. Plasma Pazopanib Concentrations Before Dosing and at 2, 4, and 8 Hours After Dosing on Day 1 and Week 3 [Day 1 and Week 3]

   The concentration of pazopanib in the plasma was measured.

10. Baseline Expression Levels of the Indicated Target Proteins in Pazopanib- and Placebo-treated Participants [Baseline]

    Baseline plasma samples were obtained from participants and were tested for the indicated cytokine and angiogenesis factors. Protein levels were determined using the Searchlight multiplex system based on chemiluminescence.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

A patient will be considered for inclusion in this study only if all of the following criteria apply:

• Signed written informed consent.

• Diagnosis of clear cell RCC that is predominantly clear cell histology. Note: cytology cannot be the only pathologic criteria to confirm clear cell RCC. Patients with tumor types that are interpreted as non-clear cell, e.g. papillary, are excluded.

• Locally advanced RCC (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to American Joint Committee on Cancer (AJCC) staging.

• Note: If the metastatic disease is restricted to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology. Cytology cannot be the only pathologic criteria to confirm clear cell RCC, but can be used in a patient with histologically confirmed clear cell RCC to confirm that metastatic disease is neoplastic in nature.

• Must have measurable disease, i.e. presenting with at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST). A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques, or ≥ 10 mm with spiral CT scan.

• Note: Patient should be excluded if all baseline measurable lesions are within previously irradiated areas.

• Note: A patient must complete all the baseline disease assessments in order to be eligible. Baseline head, chest, abdominal and pelvic CT or MRI scans must be performed within 2 weeks prior to the first dose of study medication; baseline bone scan must be performed within 3 weeks of the first dose of study medication.

• Patients who have received only one prior systemic treatment for locally advanced or metastatic RCC with documented disease progression or documented treatment discontinuation due to unacceptable toxicity. This first-line systemic treatment must be cytokine based.

• Note: The first-line cytokine-based treatment can be interleukin-2 (IL-2) or interferon-α (INFα) monotherapy, IL-2 in combination with INF-α, IL-2 and/or INF-α in combination with chemotherapy, hormonal or other therapies excluding agents targeting angiogenesis pathways. Agents in a combination regimen can be given sequentially if the treatment sequence is pre-determined and the patient does not fail one agent prior to starting another.

• Note: Prior adjuvant or neo-adjuvant therapies are permitted excluding any agents that target vascular endothelial growth factor (VEGF) or VEGF receptors. The adjuvant/neo-adjuvant therapies should not be considered as first-line systemic treatment for advanced RCC.

Or,

• Patients who have received no prior systemic therapy for advanced/metastatic RCC can be enrolled if under any of the following circumstances:

• Patients who live in countries or regions where there is no established standard first-line therapy for advanced/metastatic RCC or where there are barriers to the access of established therapies such as sunitinib, sorafenib, IFNα or IL-2.

• Patients who live in countries or regions where IL-2 or INF-α has been approved for the treatment of advanced/metastatic RCC, however, these agents are generally not recognized by the local clinical community as a standard treatment for advanced/metastatic RCC, or where the physician and the patient have determined that the available cytokine therapies are not an acceptable therapeutic option.

• Patients who have recurred following prior adjuvant or neo-adjuvant cytokine therapy for RCC are eligible to participate without receiving a first-line systemic treatment for locally advanced or metastatic RCC. These patients should be stratified as the first-line population.

• Male or female ≥ 18 years of age.

• A woman is eligible to participate in the study if she is of:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:

• Has had a hysterectomy,

• Has had a bilateral oophorectomy (ovariectomy),

• Has had a bilateral tubal ligation,

• Is post-menopausal (total cessation of menses for ≥1 year).

• Childbearing potential, has a negative serum pregnancy test within 2 weeks of the first dose of study medication, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

• An intrauterine device with a documented failure rate of less than 1% per year.

• Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female.

• Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, and for at least 21 days after the last dose of investigational product.

• Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

• Oral contraceptives are not reliable due to the potential for drug-drug interactions.

• A man with a female partner of childbearing potential is eligible to enter and participate in the study if he is abstinent or uses a barrier method of contraception during the study.

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

• Adequate baseline organ function defined as:

• Hematologic function:

Absolute Neutrophil Count (ANC) ≥1 x 10^{9/L Hemoglobin ≥ 9 g/dL Platelet ≥75 x 10}9/L

• Hepatic function:

Total bilirubin ≥ 1.5 x Upper Limit of Normal (ULN) Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≥ 2 x ULN

• Renal function:

Calculated creatinine clearance≥30 mL/min [See Section 14.6 Appendix 6] and

≥Urine protein is 0, trace, or +1 determined by dipstick urinalysis, or < 1.0 gram determined by 24-hour urine protein analysis.

• Note: A patient should first be screened with dipstick urinalysis. If urine protein is ≥2+, then a 24-hour urine protein must be assessed and patient will be excluded if 24-hour urine protein is≥ 1.0 gram.

• Corrected serum calcium level within normal range per local clinical laboratory standard.

Note: Patients with hypercalcemia should be treated until the corrected serum calcium level reaches the normal range.

• At least 4 weeks must have elapsed since the last surgery and 2 weeks must have elapsed since radiotherapy or the last systemic cytokine therapy.

• Complete recovery from prior surgery, and/or reduction of all AEs to Grade 1 from prior systemic therapy or radiotherapy.

• Note: In patients with prior radiotherapy, the steroid doses should be stable or decreasing for at least 2 weeks.

Exclusion Criteria:

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

• Pregnant or lactating female.

• History of another malignancy.

• Note: Patients who have had another malignancy and have been disease-free for 5 years, or patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.

• History or presence of central nervous system (CNS) metastasis or leptomeningeal tumors as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.

Note: A baseline brain CT or MRI scan must be obtained in all patients within 2 weeks of the first dose of study medication.

• Malabsorption syndrome or disease that significantly affects gastrointestinal function, or major resection of the stomach or small bowel that could affect the absorption of pazopanib.

• Unable to swallow and retain orally administered medication.

• 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 4 weeks prior to beginning study treatment.

• History of human immunodeficiency virus infection.

• Presence of uncontrolled infection.

• Corrected QT interval (QTc) prolongation defined as QTc interval > 470 msecs.

• History of Class III or IV congestive heart failure according to New York Heart Association (NYHA) classification.

• History of any one of the following cardiac conditions within the past 6 months:

• Cardiac angioplasty or stenting, or

• Myocardial infarction, or

• Unstable angina.

• History of cerebrovascular accident within the past 6 months.

• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140mmHg, or diastolic blood pressure (DBP) of ≥ 90mmHg].

• Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. The blood pressure must be re-assessed on two occasions that are separated by a minimum of 24 hours. The mean SBP / DBP values from both blood pressure assessments must be < 140/90mmHg in order for a patient to be eligible for the study.

• History of untreated deep venous thrombosis (DVT) within the past 6 months (e.g. a calf vein thrombosis that is not treated).

Note: Patients with recent DVT who are treated with therapeutic anti-coagulating agents (excluding therapeutic warfarin) for at least 2 weeks are eligible.

• Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.

• Evidence of bleeding diathesis or coagulopathy.

• Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.

• Has taken any prohibited medications within 14 days of the first dose of study medication.

• Current or prior use of an investigational anti-cancer drug within 4 weeks of start of study.

• Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Capital Federal	Buenos Aires	Argentina	C1405CUB
2	GSK Investigational Site	Cordoba	Córdova	Argentina	5000
3	GSK Investigational Site	Córdoba	Córdova	Argentina	5000
4	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000KZE
5	GSK Investigational Site	Quilmes		Argentina	1878
6	GSK Investigational Site	Tucuman		Argentina	4000
7	GSK Investigational Site	St Leonards	New South Wales	Australia	2065
8	GSK Investigational Site	Waratah	New South Wales	Australia	2298
9	GSK Investigational Site	Hobart	Tasmania	Australia	7000
10	GSK Investigational Site	Heidelberg	Victoria	Australia	3084
11	GSK Investigational Site	Wodonga	Victoria	Australia	3690
12	GSK Investigational Site	Salzburg		Austria	A-5020
13	GSK Investigational Site	Vienna		Austria	1130
14	GSK Investigational Site	Vienna		Austria	A-1090
15	GSK Investigational Site	Vienna		Austria	A-1100
16	GSK Investigational Site	Belo Horizonte	Minas Gerais	Brazil	30150-270
17	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90610 000
18	GSK Investigational Site	Jaú	São Paulo	Brazil	17210-120
19	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7500921
20	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7591046
21	GSK Investigational Site	Viña del Mar	Valparaíso	Chile	254-0364
22	GSK Investigational Site	Beijing		China	100034
23	GSK Investigational Site	Beijing		China	100853
24	GSK Investigational Site	Brno		Czech Republic	656 53
25	GSK Investigational Site	Chomutov		Czech Republic	430 12
26	GSK Investigational Site	Ostrava - Poruba		Czech Republic	708 52
27	GSK Investigational Site	Praha 2		Czech Republic	12808
28	GSK Investigational Site	Tallinn		Estonia	11619
29	GSK Investigational Site	Tartu		Estonia	51014
30	GSK Investigational Site	Athens		Greece	115 22
31	GSK Investigational Site	Athens		Greece	115 26
32	GSK Investigational Site	Athens		Greece	115 28
33	GSK Investigational Site	Athens		Greece	185 37
34	GSK Investigational Site	Patra		Greece	26500
35	GSK Investigational Site	Thessaloniki		Greece	564 29
36	GSK Investigational Site	Hong Kong		Hong Kong
37	GSK Investigational Site	Kowloon		Hong Kong
38	GSK Investigational Site	Tuen Mun, New Territories		Hong Kong
39	GSK Investigational Site	Bangalore		India	560029
40	GSK Investigational Site	Hyderabad		India	500033
41	GSK Investigational Site	Mumbai		India	400026
42	GSK Investigational Site	Pune		India	411 004
43	GSK Investigational Site	Trivandrum		India	695011
44	GSK Investigational Site	Galway		Ireland
45	GSK Investigational Site	Tallaght, Dublin		Ireland	24
46	GSK Investigational Site	Roma	Lazio	Italy	00133
47	GSK Investigational Site	Roma	Lazio	Italy	00152
48	GSK Investigational Site	Casalpusterlengo (LO)	Lombardia	Italy	26841
49	GSK Investigational Site	Crema	Lombardia	Italy	26013
50	GSK Investigational Site	Milano	Lombardia	Italy	20132
51	GSK Investigational Site	Rozzano (MI)	Lombardia	Italy	20089
52	GSK Investigational Site	Orbassano (TO)	Piemonte	Italy	10043
53	GSK Investigational Site	Seoul		Korea, Republic of	110-744
54	GSK Investigational Site	Seoul		Korea, Republic of	120-752
55	GSK Investigational Site	songpa-gu, Seoul		Korea, Republic of	138-736
56	GSK Investigational Site	Riga		Latvia	LV 1002
57	GSK Investigational Site	Kaunas		Lithuania	LT-50009
58	GSK Investigational Site	Klaipeda		Lithuania	LT-92228
59	GSK Investigational Site	Vilnius		Lithuania	LT-08660
60	GSK Investigational Site	Guadalajara	Jalisco	Mexico	CP44280
61	GSK Investigational Site	Merida	Yucatán	Mexico	97500
62	GSK Investigational Site	Mexico City		Mexico	CP 14080
63	GSK Investigational Site	Christchurch		New Zealand	8001
64	GSK Investigational Site	Newtown, Wellington		New Zealand	6002
65	GSK Investigational Site	Palmerston North		New Zealand	4414
66	GSK Investigational Site	Islamabad		Pakistan	1590
67	GSK Investigational Site	Karachi		Pakistan	74800
68	GSK Investigational Site	Lahore		Pakistan	54600
69	GSK Investigational Site	Gdansk		Poland	80-210
70	GSK Investigational Site	Krakow		Poland	31-115
71	GSK Investigational Site	Kraków		Poland	31-108
72	GSK Investigational Site	Olsztyn		Poland	10-226
73	GSK Investigational Site	Olsztyn		Poland	10-228
74	GSK Investigational Site	Poznan		Poland	60-569
75	GSK Investigational Site	Warszawa		Poland	00-909
76	GSK Investigational Site	Chelyabinsk		Russian Federation	454087
77	GSK Investigational Site	Kazan		Russian Federation	420029
78	GSK Investigational Site	Moscow		Russian Federation	115 478
79	GSK Investigational Site	Moscow		Russian Federation	117 837
80	GSK Investigational Site	Moscow		Russian Federation	129 128
81	GSK Investigational Site	Omsk		Russian Federation	644013
82	GSK Investigational Site	Samara		Russian Federation	443066
83	GSK Investigational Site	St. Petersburg		Russian Federation	198255
84	GSK Investigational Site	Voronezh		Russian Federation	394062
85	GSK Investigational Site	Yaroslavl		Russian Federation	150054
86	GSK Investigational Site	Bratislava		Slovakia	833 10
87	GSK Investigational Site	Sfax		Tunisia	3000
88	GSK Investigational Site	Sousse		Tunisia	4054
89	GSK Investigational Site	Tunis		Tunisia	1007
90	GSK Investigational Site	Tunis		Tunisia	1008
91	GSK Investigational Site	Donetsk		Ukraine	83092
92	GSK Investigational Site	Kharkiv		Ukraine	61037
93	GSK Investigational Site	Kyiv		Ukraine	03115
94	GSK Investigational Site	Lviv		Ukraine	79031
95	GSK Investigational Site	Zaporizhzhya		Ukraine	69600
96	GSK Investigational Site	Exeter	Devon	United Kingdom	EX2 5DW
97	GSK Investigational Site	Manchester	Lancashire	United Kingdom	M20 4BX
98	GSK Investigational Site	Bebington, Wirral		United Kingdom	CH63 4JY
99	GSK Investigational Site	Belfast		United Kingdom	BT9 7AB
100	GSK Investigational Site	Swansea		United Kingdom	SA2 8QA

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bonate PL, Suttle AB. Modeling tumor growth kinetics after treatment with pazopanib or placebo in patients with renal cell carcinoma. Cancer Chemother Pharmacol. 2013 Jul;72(1):231-40. doi: 10.1007/s00280-013-2191-0. Epub 2013 May 29.
• Maitland ML, Wu K, Sharma MR, Jin Y, Kang SP, Stadler WM, Karrison TG, Ratain MJ, Bies RR. Estimation of renal cell carcinoma treatment effects from disease progression modeling. Clin Pharmacol Ther. 2013 Apr;93(4):345-51. doi: 10.1038/clpt.2012.263. Epub 2012 Dec 27.
• Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. doi: 10.1200/JCO.2009.23.9764. Epub 2010 Jan 25.
• Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12.
• Tran HT, Liu Y, Zurita AJ, Lin Y, Baker-Neblett KL, Martin AM, Figlin RA, Hutson TE, Sternberg CN, Amado RG, Pandite LN, Heymach JV. Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol. 2012 Aug;13(8):827-37. doi: 10.1016/S1470-2045(12)70241-3. Epub 2012 Jul 2.
• Xu CF, Reck BH, Goodman VL, Xue Z, Huang L, Barnes MR, Koshy B, Spraggs CF, Mooser VE, Cardon LR, Pandite LN. Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma. J Hepatol. 2011 Jun;54(6):1237-43. doi: 10.1016/j.jhep.2010.09.028. Epub 2011 Feb 12.
• Xu CF, Reck BH, Xue Z, Huang L, Baker KL, Chen M, Chen EP, Ellens HE, Mooser VE, Cardon LR, Spraggs CF, Pandite L. Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00334282
• Other Study ID Numbers: VEG105192
• First Posted: Jun 7, 2006
• Last Update Posted: Feb 5, 2016
• Last Verified: Aug 1, 2015

• Keywords provided by GlaxoSmithKline: Metastatic; Anti-angiogenesis; GW786034; Pazopanib
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell

Study Results

Participant Flow

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching Placebo administered orally once a day
Period Title: Overall Study
STARTED	290	145
COMPLETED	68	37
NOT COMPLETED	222	108

Baseline Characteristics

Arm/Group Title	Pazopanib 800 mg	Placebo	Total
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching Placebo administered once a day	Total of all reporting groups
Overall Participants	290	145	435
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (10.06)	59.6 (11.04)	59.3 (10.38)
Sex: Female, Male (Count of Participants)
Female	92 31.7%	36 24.8%	128 29.4%
Male	198 68.3%	109 75.2%	307 70.6%
Race/Ethnicity, Customized (participants) [Number]
White	252 86.9%	122 84.1%	374 86%
Asian	36 12.4%	23 15.9%	59 13.6%
African American/African Heritage	1 0.3%	0 0%	1 0.2%
Native Hawaiian or other Pacific Islander	1 0.3%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause. Assessments of progression and non-progression were made by an independent imaging review committee (IRC) for the primary analysis.
Time Frame	Randomization until progression (up to 2 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching Placebo administered once a day
Measure Participants	290	145
Median (95% Confidence Interval) [months]	9.2	4.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pazopanib 800 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.0000001
	Comments	stratified log-rank test
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.46
	Confidence Interval	() 95%; 0.34 to 0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value is the hazard ratio comparing pazopanib to placebo.

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from randomization until death. The length of this interval was estimated as the date of death minus the date of randomization plus 1 day. Participants who were still alive at the time of analysis were censored.
Time Frame	Randomization until death (up to 2 years)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching Placebo administered orally once a day
Measure Participants	290	145
Median (95% Confidence Interval) [months]	22.9	20.5

3. Secondary Outcome

Title	Overall Response
Description	Overall response is the number of participants who had a complete response (CR) or a partial response (PR). Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the Baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease, small changes that do not meet previously given criteria. IRC, independent review committee.
Time Frame	Baseline until either response or progression (up to 2 years)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching Placebo administered orally once a day
Measure Participants	290	145
Complete Response, IRC assessed	1 0.3%	0 0%
Partial Response, IRC assessed	87 30%	5 3.4%
Stable Disease, IRC assessed	110 37.9%	59 40.7%
Progressive Disease, IRC assessed	51 17.6%	58 40%
Unknown, IRC assessed	41 14.1%	23 15.9%
Complete Response, Investigator assessed	4 1.4%	0 0%
Partial Response, Investigator assessed	99 34.1%	9 6.2%
Stable Disease, Investigator assessed	118 40.7%	62 42.8%
Progressive Disease, Investigator assessed	46 15.9%	65 44.8%
Unknown, Investigator assessed	23 7.9%	9 6.2%

4. Secondary Outcome

Title	Participants With Complete Response, Partial Response, or 6 Months of Stable Disease
Description	This is similar to overall response rate, but also includes participants who had stable disease for at least 6 months. Per Response Evaluation Criteria In Solid Tumors (RECIST): CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the Baseline sum; Stable Disease, small changes that do not meet previously given criteria; Progressive Disease, a >=20% increase in target lesions. IRC, independent review committee.
Time Frame	Baseline until 6 months post-Baseline or progressive disease

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching placebo administered orally once a day
Measure Participants	290	145
Complete Response, IRC assessed	1 0.3%	0 0%
Partial Response, IRC assessed	87 30%	5 3.4%
6 Months Stable Disease, IRC assessed	48 16.6%	17 11.7%
Progressive Disease, IRC assessed	92 31.7%	84 57.9%
Unknown	62 21.4%	39 26.9%

5. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined as the time from first observation of response until progression of disease or death.
Time Frame	Time from response until progression (up to 2 years)

Outcome Measure Data

Analysis Population Description

ITT Population. Only results for pazopanib are given because there were not enough placebo responders.

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day
Measure Participants	290
Median (95% Confidence Interval) [weeks]	58.7

6. Secondary Outcome

Title	Time to Response as Assessed by an Independent Review Committee (IRC) and the Investigator
Description	Time to response is defined as the time from randomization until the first documented evidence of complete response (all detectable tumor has disappeared) or partial response (a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the Baseline sum) (whichever status was recorded first).
Time Frame	Randomization until CR or PR (assessed for up to 2 years)

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants with a complete or partial response were analyzed. Only results for pazopanib are given because there were not enough placebo responders. The different number of participants analyzed is due to differences in clinical judgement, measurement, and the selection of target lesions.

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day
Measure Participants	103
IRC assessed, n=88	11.9
Investigator assessed, n=103	12.0

7. Secondary Outcome

Title	Adjusted Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 (EORTC QLQ C-30) Score at Weeks 6, 12, 18, 24, and 48
Description	The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer participants. The analyses for EORTC QLQ-C30 were focused on global health status/Health-Related Quality of Life (HRQOL) scores on the questionnaire. The scores (from 1 [very poor quality of life] to 7 [excellent quality of life]) for these two questions were averaged and then transformed to a 0 - 100 scale (based on published methods) prior to analysis of change from Baseline.
Time Frame	Baseline and Weeks 6, 12, 18, 24, and 48

Outcome Measure Data

Analysis Population Description

Participants in the ITT Population who completed HRQOL assessments at Baseline and had at least one post-Baseline assessment are included. Only participants who were on treatment at the given time point were asked to complete the questionnaire, and only those who completed the questionnaire could be analyzed for each individual time point.

Arm/Group Title	Pazopanib	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching placebo administered orally once a day
Measure Participants	246	111
Week 6, n=243, 110	-3.2 (19.66)	-2.6 (19.18)
Week 12, n=219, 81	-3.6 (20.16)	-0.5 (17.55)
Week 18, n=191, 61	-2.5 (21.70)	-0.3 (18.13)
Week 24, n=164, 49	0.1 (19.81)	-0.5 (18.67)
Week 48, n=96, 24	-0.3 (18.36)	0.3 (15.63)

8. Secondary Outcome

Title	Adjusted Mean Change From Baseline in the Index Score of the EQ-5D (EuroQoL [Quality of Life]-5D) Questionnaire at Weeks 6, 12, 18, 24, and 48
Description	The EQ-5D is comprised of a 5-item health status measure and a visual analogue rating scale, and measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (no, moderate, and extreme problems). Scoring of the EQ-5D yields an index-based summary score (Index), through application of societal weights, and a VAS score (VAS). Index is interpreted on a continuum from 1.0 (best possible health) to 0 (represents dead), to some health sates being worse than dead (<0).
Time Frame	Baseline and Weeks 6, 12, 18, 24, and 48

Outcome Measure Data

Analysis Population Description

Participants in the ITT Population who completed HRQOL assessments at Baseline and had at least one post-baseline assessment are included. Only participants who were on treatment at the given time point were asked to complete the questionnaire, and only those who completed the questionnaire could be analyzed for each individual time point.

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching placebo administered orally once a day
Measure Participants	253	125
Week 6, n=253, 125	-0.014 (0.2203)	-0.029 (0.2674)
Week 12, n=219, 86	-0.040 (0.2148)	0.007 (0.1969)
Week 18, n=196, 62	-0.023 (0.2305)	-0.006 (0.1466)
Week 24, n=166, 51	-0.025 (0.2420)	-0.001 (0.2411)
Week 36, n=98, 24	0.030 (0.1961)	-0.005 (0.2015)

9. Secondary Outcome

Title	Adjusted Mean Change From Baseline in the Visual Analog Scale (VAS) Score of the EQ-5D (EuroQoL [Quality of Life]-5D) Questionnaire at Weeks 6, 12, 18, 24, and 48
Description	The EQ-5D is comprised of a 5-item health status measure and a visual analogue rating scale, and measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (no, moderate, and extreme problems). Scoring of the EQ-5D yields an index-based summary score (Index) and a VAS score (VAS), obtained from participant's self-reports of their health on a VAS thermometer scale. The EQ-5D VAS ranges from 0% (worst imaginable health state) to 100% (best imaginable health state).
Time Frame	Baseline and Weeks 6, 12, 18, 24, and 48

Outcome Measure Data

Analysis Population Description

Participants in the ITT Population who completed HRQOL assessments at Baseline and had at least one post-Baseline assessment are included. Only participants who were on treatment at the given time point were asked to complete the questionnaire, and only those who completed the questionnaire could be analyzed for each individual time point.

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching placebo administered orally once a day
Measure Participants	239	111
Week 12, n=212, 80	-0.9 (21.07)	-3.6 (23.04)
Week 6, n=239, 111	0.4 (22.55)	0.2 (25.35)
Week 18, n=189, 60	0.1 (23.20)	0.1 (19.35)
Week 24, n=161, 49	2.6 (22.16)	5.4 (21.27)
Week 36, n=95, 23	2.4 (24.21)	8.8 (23.96)

10. Secondary Outcome

Title	Plasma Pazopanib Concentrations Before Dosing and at 2, 4, and 8 Hours After Dosing on Day 1 and Week 3
Description	The concentration of pazopanib in the plasma was measured.
Time Frame	Day 1 and Week 3

Outcome Measure Data

Analysis Population Description

Subgroup of enrolled participants who agreed to have blood samples collected for analysis of pazopanib in plasma. Data were missing or not collected at Week 3 for 8 participants for whom data were available on Day 1. No samples were collected at Week 3 from 2 participants.

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 mg (tablets) administered once daily
Measure Participants	57
Day 1, before dosing, n=57	0
Week 3, before dosing, n=48	31851
Day 1, 2 hours after dosing, n=57	17270
Week 3, 2 hours after dosing, n=49	42205
Day 1, 4 hours after dosing, n=57	24360
Week 3, 4 hours after dosing, n=49	42637
Day 1, 8 hours after dosing, n=57	19925
Week 3, 8 hours after dosing, n=48	40177.5

11. Secondary Outcome

Title	Baseline Expression Levels of the Indicated Target Proteins in Pazopanib- and Placebo-treated Participants
Description	Baseline plasma samples were obtained from participants and were tested for the indicated cytokine and angiogenesis factors. Protein levels were determined using the Searchlight multiplex system based on chemiluminescence.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Subgroup of enrolled participants who agreed to have plasma samples collected for biomarker analyses.

Arm/Group Title	Pazopanib 800 mg	Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day	Matching placebo administered orally once a day
Measure Participants	225	119
Interleukin-6	31.003 (65.247)	24.145 (31.708)
Interleukin-8	35.429 (164.12)	27.755 (66.129)
Vascular endothelial growth factor	308.61 (365.19)	273.15 (350.91)
Hepatocyte growth factor	383.55 (308.89)	522.94 (1003.8)
Tissue inhibitor of metalloproteinase 1	847464 (690744)	735915 (423493)
e-Selectin	41649.28 (22389.04)	41231.45 (19825.7)
Osteopotin	444343 (707005)	369317 (490931)

Adverse Events

Time Frame	Date of study entry until 28 days after the last dose.
Arm/Group Title	Pazopanib 800 mg		Placebo
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day		Matching Placebo administered orally once a day
All Cause Mortality
	Pazopanib 800 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pazopanib 800 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/290 (27.2%)		28/145 (19.3%)
Blood and lymphatic system disorders
Anaemia	6/290 (2.1%)		4/145 (2.8%)
Leukopenia	1/290 (0.3%)		0/145 (0%)
Cardiac disorders
Myocardial ischaemia	2/290 (0.7%)		0/145 (0%)
Acute myocardial infarction	1/290 (0.3%)		0/145 (0%)
Atrial fibrillation	2/290 (0.7%)		0/145 (0%)
Bradycardia	1/290 (0.3%)		0/145 (0%)
Cardiac arrest	1/290 (0.3%)		0/145 (0%)
Cardiac failure	1/290 (0.3%)		0/145 (0%)
Myocardial infarction	3/290 (1%)		0/145 (0%)
Ear and labyrinth disorders
Vertigo	1/290 (0.3%)		0/145 (0%)
Gastrointestinal disorders
Diarrhea	6/290 (2.1%)		0/145 (0%)
Vomiting	4/290 (1.4%)		2/145 (1.4%)
Abdominal pain	2/290 (0.7%)		1/145 (0.7%)
Abdominal pain upper	2/290 (0.7%)		1/145 (0.7%)
Intestinal obstruction	2/290 (0.7%)		0/145 (0%)
Abdominal distension	0/290 (0%)		1/145 (0.7%)
Constipation	1/290 (0.3%)		0/145 (0%)
Enterocutaneous fistula	1/290 (0.3%)		0/145 (0%)
Gastric haemorrhage	1/290 (0.3%)		0/145 (0%)
Gastrointestinal haemorrhage	0/290 (0%)		1/145 (0.7%)
Irritable bowel syndrome	1/290 (0.3%)		0/145 (0%)
Nausea	1/290 (0.3%)		0/145 (0%)
Oesophageal haemorrhage	1/290 (0.3%)		0/145 (0%)
Rectal haemorrhage	1/290 (0.3%)		0/145 (0%)
Retroperitoneal haemorrhage	1/290 (0.3%)		0/145 (0%)
Gastritis	1/290 (0.3%)		0/145 (0%)
Anorectal varices haemorrhage	1/290 (0.3%)		0/145 (0%)
General disorders
Asthenia	0/290 (0%)		2/145 (1.4%)
Chest pain	1/290 (0.3%)		0/145 (0%)
Fatigue	0/290 (0%)		1/145 (0.7%)
Hernia	0/290 (0%)		1/145 (0.7%)
Pain	0/290 (0%)		1/145 (0.7%)
Pyrexia	1/290 (0.3%)		0/145 (0%)
Sudden death	0/290 (0%)		1/145 (0.7%)
Hepatobiliary disorders
Hepatic function abnormal	2/290 (0.7%)		1/145 (0.7%)
Hepatotoxicity	3/290 (1%)		0/145 (0%)
Jaundice cholestatic	1/290 (0.3%)		1/145 (0.7%)
Hyperbilirubinaemia	1/290 (0.3%)		0/145 (0%)
Immune system disorders
Anaphylactic reaction	1/290 (0.3%)		0/145 (0%)
Infections and infestations
Peritonitis	1/290 (0.3%)		0/145 (0%)
Pneumonia	2/290 (0.7%)		1/145 (0.7%)
Upper respiratory tract infection	0/290 (0%)		2/145 (1.4%)
Appendicitis	0/290 (0%)		1/145 (0.7%)
Bronchitis	1/290 (0.3%)		0/145 (0%)
Bronchopneumonia	1/290 (0.3%)		0/145 (0%)
Ear infection	0/290 (0%)		1/145 (0.7%)
Herpes zoster	1/290 (0.3%)		0/145 (0%)
Infection	1/290 (0.3%)		0/145 (0%)
Lower respiratory tract infection	0/290 (0%)		1/145 (0.7%)
Septic shock	1/290 (0.3%)		0/145 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/290 (0%)		2/145 (1.4%)
Contusion	0/290 (0%)		1/145 (0.7%)
Lower limb fracture	1/290 (0.3%)		0/145 (0%)
Skin graft failure	1/290 (0.3%)		0/145 (0%)
Investigations
Alanine aminotransferase increasead	2/290 (0.7%)		1/145 (0.7%)
Blood creatinine increased	2/290 (0.7%)		1/145 (0.7%)
Aspartate aminotransferase increased	0/290 (0%)		1/145 (0.7%)
Blood bilirubin increased	0/290 (0%)		1/145 (0.7%)
Blood urea increased	0/290 (0%)		1/145 (0.7%)
Electrocardiogram QT prolonged	1/290 (0.3%)		0/145 (0%)
Haemoglobin decreased	1/290 (0.3%)		0/145 (0%)
Neutrophil count decreased	1/290 (0.3%)		0/145 (0%)
Metabolism and nutrition disorders
Dehydration	2/290 (0.7%)		2/145 (1.4%)
Decreased appetite	1/290 (0.3%)		1/145 (0.7%)
Hyperkalaemia	2/290 (0.7%)		0/145 (0%)
Cachexia	0/290 (0%)		1/145 (0.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/290 (0.3%)		0/145 (0%)
Musculoskeletal pain	0/290 (0%)		1/145 (0.7%)
Pathological fracture	0/290 (0%)		1/145 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	2/290 (0.7%)		0/145 (0%)
Basal cell carcinoma	1/290 (0.3%)		0/145 (0%)
Neoplasm	0/290 (0%)		1/145 (0.7%)
Squamous cell carcinoma	1/290 (0.3%)		0/145 (0%)
Nervous system disorders
Seizure	1/290 (0.3%)		1/145 (0.7%)
Paraplegia	1/290 (0.3%)		1/145 (0.7%)
Cerebrovascular insufficiency	1/290 (0.3%)		0/145 (0%)
Coordination abnormal	0/290 (0%)		1/145 (0.7%)
Dizziness	0/290 (0%)		1/145 (0.7%)
Ischaemic stroke	1/290 (0.3%)		0/145 (0%)
Myelitis	1/290 (0.3%)		0/145 (0%)
Speech disorder	0/290 (0%)		1/145 (0.7%)
Transient ischaemic attack	1/290 (0.3%)		0/145 (0%)
Psychiatric disorders
Confusional state	2/290 (0.7%)		0/145 (0%)
Renal and urinary disorders
Acute kidney injury	0/290 (0%)		2/145 (1.4%)
Haematuria	1/290 (0.3%)		0/145 (0%)
Renal haemorrhage	1/290 (0.3%)		0/145 (0%)
Renal vein thrombosis	0/290 (0%)		1/145 (0.7%)
Urinary retention	1/290 (0.3%)		0/145 (0%)
Reproductive system and breast disorders
Pelvic pain	1/290 (0.3%)		0/145 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	6/290 (2.1%)		3/145 (2.1%)
Haemoptysis	4/290 (1.4%)		1/145 (0.7%)
Pleural effusion	3/290 (1%)		1/145 (0.7%)
Acute pulmonary oedema	0/290 (0%)		1/145 (0.7%)
Cough	0/290 (0%)		1/145 (0.7%)
Pneumothorax	1/290 (0.3%)		0/145 (0%)
Pleurisy	1/290 (0.3%)		0/145 (0%)
Pulmonary embolism	2/290 (0.7%)		0/145 (0%)
Pulmonary haemorrhage	1/290 (0.3%)		0/145 (0%)
Epistaxis	0/290 (0%)		1/145 (0.7%)
Skin and subcutaneous tissue disorders
Rash	1/290 (0.3%)		0/145 (0%)
Skin lesion	1/290 (0.3%)		0/145 (0%)
Vascular disorders
Hypertension	2/290 (0.7%)		1/145 (0.7%)
Deep vein thrombosis	0/290 (0%)		1/145 (0.7%)
Hypertensive crisis	1/290 (0.3%)		0/145 (0%)
Other (Not Including Serious) Adverse Events
	Pazopanib 800 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	258/290 (89%)		87/145 (60%)
Blood and lymphatic system disorders
Thrombocytopenia	22/290 (7.6%)		2/145 (1.4%)
Neutropenia	15/290 (5.2%)		0/145 (0%)
Anaemia	19/290 (6.6%)		7/145 (4.8%)
Endocrine disorders
Hypothyroidism	20/290 (6.9%)		0/145 (0%)
Gastrointestinal disorders
Diarrhoea	149/290 (51.4%)		13/145 (9%)
Nausea	75/290 (25.9%)		13/145 (9%)
Vomiting	59/290 (20.3%)		12/145 (8.3%)
Abdominal pain	32/290 (11%)		2/145 (1.4%)
Abdominal pain upper	24/290 (8.3%)		8/145 (5.5%)
Constipation	20/290 (6.9%)		9/145 (6.2%)
Dyspepsia	17/290 (5.9%)		1/145 (0.7%)
General disorders
Fatigue	58/290 (20%)		13/145 (9%)
Asthenia	44/290 (15.2%)		13/145 (9%)
Pyrexia	14/290 (4.8%)		9/145 (6.2%)
Chest pain	16/290 (5.5%)		2/145 (1.4%)
Investigations
Alanine aminotransferase increased	54/290 (18.6%)		4/145 (2.8%)
Aspartate aminotransferase increased	46/290 (15.9%)		5/145 (3.4%)
Weight decreased	31/290 (10.7%)		6/145 (4.1%)
Metabolism and nutrition disorders
Decreased appetite	70/290 (24.1%)		17/145 (11.7%)
Musculoskeletal and connective tissue disorders
Back pain	23/290 (7.9%)		17/145 (11.7%)
Arthralgia	25/290 (8.6%)		14/145 (9.7%)
Pain in extremity	20/290 (6.9%)		9/145 (6.2%)
Nervous system disorders
Headache	31/290 (10.7%)		8/145 (5.5%)
Dysgeusia	25/290 (8.6%)		1/145 (0.7%)
Psychiatric disorders
Insomnia	16/290 (5.5%)		10/145 (6.9%)
Renal and urinary disorders
Proteinuria	30/290 (10.3%)		0/145 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	25/290 (8.6%)		14/145 (9.7%)
Dyspnoea	19/290 (6.6%)		8/145 (5.5%)
Skin and subcutaneous tissue disorders
Hair colour changes	109/290 (37.6%)		5/145 (3.4%)
Rash	24/290 (8.3%)		4/145 (2.8%)
Alopecia	24/290 (8.3%)		1/145 (0.7%)
Palmar-plantar erythrodysaesthesia syndrome	17/290 (5.9%)		1/145 (0.7%)
Vascular disorders
Hypertension	115/290 (39.7%)		16/145 (11%)

Limitations/Caveats

[Not Specified]

More Information

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.