GW786034 In Subjects With Locally Recurrent Or Metastatic Clear Cell Renal Cell Carcinoma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00244764
• Collaborator: (none)
• Enrollment: 225
• Locations: 45
• Arms: 2
• Duration (Months): 95
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase II, multi-center, two-stage study utilising a randomised discontinuation design to evaluate the safety and efficacy of GW786034 (pazopanib) in adult subjects with locally recurrent or metastatic clear-cell Renal Cell Carcinoma (RCC). After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: GW786034; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 225 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of GW786034 Using a Randomised Discontinuation Design in Subjects With Locally Recurrent or Metastatic Clear-Cell Renal Cell Carcinoma
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pazopanib All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.	Drug: GW786034; All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.
Placebo Comparator: Placebo All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.	Drug: Placebo; All patients receive GW786034. At week 12, some subjects will be randomized based on response (SD) and the others will remain on drug. After the interim analysis, the design was changed to an open label, single arm study with all subjects receiving pazopanib.

Outcome Measures

Primary Outcome Measures

1. Overall Response by RECIST Criteria [Baseline to Response (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.]

   The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the 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, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria.

2. Stable Disease at 12 Weeks - Interim Analysis of First 60 Participants [Week 12]

   The protocol called for an interim analysis of the first 60 participants to determine their status at Week 12, and to determine the number of participants with stable disease, although all categories were reported. Stable disease is defined as a disease that has not grown enough to be called progressive disease and has not shrunk enough to be called partial/complete response.

Secondary Outcome Measures

1. Duration of Response [First response until progression of disease (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.]

   Using RECIST criteria: date of first confirmed tumor response (CR or PR) to date of tumor progression or to death. Participants who did not progress or die were censored at their last radiologic assessment. Only participants who had a response were analyzed.

2. Progression-free Survival [From the first day of treatment to the earliest date of disease progression or death due to any cause (up to 2.40 years)]

   Progression-free Survival is defined as the interval between the first day of treatment and the earliest date of disease progression or death due to any cause, whichever occurred first. Progressive disease is defined as a >=20% increase in target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Histologically or cytologically confirmed diagnosis of Renal Cell Carcinoma of predominantly clear-cell histology (excluding chromophobe, papillary, collecting duct, and undifferentiated tumors) which is metastatic or locally recurrent

• Either no prior systemic therapy or failed only 1 prior cytokine-based or bevacizumab-based therapy

• Evidence of documented measurable disease by RECIST criteria

• Male or female at least 21 years of age

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

1. 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).

1. Childbearing potential, has a negative serum pregnancy test at Screening Period and serum or urine pregnancy test at Day1, 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 (IUD) with a documented failure rate of less than 1% per year.

• Vasectomized partner who is sterile prior to the female subject'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).

A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception (e.g. condom) or abstinence during the study and for 28 days following the last dose of investigational drug.

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

• Adequate bone marrow function.

• Adequate hepatic function.

• Adequate renal function.

• Adequate PT/PTT or INR/aPTT.

• Able to swallow and retain oral medications.

• Written informed consent.

Exclusion criteria:

• Received prior non-cytokine or non-bevacizumab therapies .

• Received chemotherapy for renal cell carcinoma.

• Have had any major surgery, radiotherapy, or immunotherapy within the last 28 days and/or not recovered from prior therapy.

• History of hypercalcemia within two months of start of therapy.

• Patients who are pregnant or lactating.

• Poorly controlled hypertension.

• QTc prolongation defined as a QTc interval ≥ 480 msecs or other significant ECG abnormalities.

• Has Class II, III or IV heart failure as defined by the New York Heart Association functional classification system. A subject who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible.

• Any history of cerebrovascular accident [CVA].

• History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks.

• History of venous thrombosis in last 12 weeks.

• Current use of therapeutic warfarin.

• Use of antiplatelet agents other than aspirin (≤ 325 mg/day).

• Leptomeningeal or brain metastases.

• Prior history of malignancies other than renal cell carcinoma (except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or the subject has been free of any other malignancies for > 5 years).

• Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or obtaining informed consent.

• History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Has any unresolved bowel obstruction or diarrhea.

• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

• Is on any specifically prohibited medication or requires any of these medications during treatment with GW786034.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Duarte	California	United States	91010-3000
2	GSK Investigational Site	Los Angeles	California	United States	90095
3	GSK Investigational Site	Orange	California	United States	92868
4	GSK Investigational Site	San Francisco	California	United States	94115
5	GSK Investigational Site	Aurora	Colorado	United States	80010
6	GSK Investigational Site	Tucker	Georgia	United States	30084
7	GSK Investigational Site	Indianapolis	Indiana	United States	46202
8	GSK Investigational Site	New York	New York	United States	10032-3713
9	GSK Investigational Site	Cleveland	Ohio	United States	44106
10	GSK Investigational Site	Cleveland	Ohio	United States	44195
11	GSK Investigational Site	Nashville	Tennessee	United States	37203
12	GSK Investigational Site	Dallas	Texas	United States	75246
13	GSK Investigational Site	Camperdown	New South Wales	Australia	2050
14	GSK Investigational Site	Kogarah	New South Wales	Australia	2217
15	GSK Investigational Site	Randwick	New South Wales	Australia	2031
16	GSK Investigational Site	East Melbourne	Victoria	Australia	3002
17	GSK Investigational Site	Footscay	Victoria	Australia	3011
18	GSK Investigational Site	Heidelberg	Victoria	Australia	3084
19	GSK Investigational Site	Parkville	Victoria	Australia	3050
20	GSK Investigational Site	Bruxelles		Belgium	1070
21	GSK Investigational Site	Bruxelles		Belgium	1200
22	GSK Investigational Site	Gent		Belgium	9000
23	GSK Investigational Site	Jette		Belgium	1090
24	GSK Investigational Site	Liège		Belgium	4000
25	GSK Investigational Site	Roeselare		Belgium	8800
26	GSK Investigational Site	Wilrijk		Belgium	2610
27	GSK Investigational Site	Guangzhou	Guangdong	China	510060
28	GSK Investigational Site	Nanjing	Jiangsu	China	210029
29	GSK Investigational Site	Jinan	Shandong	China	250012
30	GSK Investigational Site	Hangzhou	Zhejiang	China	310003
31	GSK Investigational Site	Beijing		China	100034
32	GSK Investigational Site	Beijing		China	100853
33	GSK Investigational Site	Shanghai		China	200040
34	GSK Investigational Site	Brno		Czech Republic	656 53
35	GSK Investigational Site	Hradec Kralove		Czech Republic	500 05
36	GSK Investigational Site	Praha 2		Czech Republic	12808
37	GSK Investigational Site	Hong Kong		Hong Kong
38	GSK Investigational Site	Kowloon		Hong Kong
39	GSK Investigational Site	Tuen Mun		Hong Kong
40	GSK Investigational Site	Haifa		Israel	31096
41	GSK Investigational Site	Petach Tikva		Israel	49100
42	GSK Investigational Site	Tel Aviv		Israel	64239
43	GSK Investigational Site	Zrifin		Israel	70300
44	GSK Investigational Site	Taipei		Taiwan	100
45	GSK Investigational Site	Taipei		Taiwan

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.
• Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. doi: 10.1200/JCO.2008.21.6994. Epub 2009 Dec 14.
• 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.
• White AJ, LaGerche A, Toner GC, Whitbourn RJ. Apical ballooning syndrome during treatment with a vascular endothelial growth factor receptor antagonist. Int J Cardiol. 2009 Jan 24;131(3):e92-4. Epub 2007 Oct 24.
• 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: NCT00244764
• Other Study ID Numbers: VEG102616
• First Posted: Oct 27, 2005
• Last Update Posted: Mar 27, 2017
• Last Verified: Sep 1, 2015

• Keywords provided by GlaxoSmithKline: Angiogenesis; Renal Cell Carcinoma; Solid tumors; Pazopanib(GW786034)
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell

Study Results

Participant Flow

Recruitment Details	This study was originally designed as a Phase II, multi-centre study utilizing a randomized discontinuation design. In the original study design, a 12-week Lead-in Phase was an open-label period during which all enrolled participans received pazopanib.
Pre-assignment Detail	All participants began with 12 weeks of open-label treatment. In the original design, participants with stable disease at Week 12 were to be randomized. After the interim analysis, the study was amended to be treated like a single-arm open-label study. Any participants who had been randomized to placebo were to be crossed back to pazopanib.

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 milligrams (mg) (tablets) administered orally once a day
Period Title: Overall Study
STARTED	225
COMPLETED	129
NOT COMPLETED	96

Baseline Characteristics

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 milligrams (mg) (tablets) administered orally once a day
Overall Participants	225
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (10.33)
Sex: Female, Male (Count of Participants)
Female	69 30.7%
Male	156 69.3%
Race/Ethnicity, Customized (participants) [Number]
White	178 79.1%
Asian-Japanese/East Asian/South East Asian HER	38 16.9%
African American/African Heritage (HER)	4 1.8%
Asian-Central/South Asian Heritage	2 0.9%
American Indian or Alaska Native and White	1 0.4%
Asian-Mixed Asian Heritage	1 0.4%
Native Hawaiian or other Pacific Islander	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Overall Response by RECIST Criteria
Description	The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the 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, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria.
Time Frame	Baseline to Response (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.

Outcome Measure Data

Analysis Population Description

All Enrolled: all participants who received at least one dose of pazopanib

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 milligrams (mg) (tablets) administered orally once a day
Measure Participants	225
Complete Response	3 1.3%
Partial Response	75 33.3%
Stable Disease	101 44.9%
Progressive Disease	24 10.7%
Not evaluable	22 9.8%
Complete Response + Partial Response	78 34.7%

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
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	34.7
	Confidence Interval	() 95%; 28.4 to 40.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value provided is the response rate.

2. Primary Outcome

Title	Stable Disease at 12 Weeks - Interim Analysis of First 60 Participants
Description	The protocol called for an interim analysis of the first 60 participants to determine their status at Week 12, and to determine the number of participants with stable disease, although all categories were reported. Stable disease is defined as a disease that has not grown enough to be called progressive disease and has not shrunk enough to be called partial/complete response.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Subset of the All Enrolled Population including only the first 60 participants

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 milligrams (mg) (tablets) administered orally once a day
Measure Participants	60
Complete Response	0 0%
Partial Response	23 10.2%
Stable Disease	25 11.1%
Progressive Disease	3 1.3%
Unknown	9 4%

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
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	42
	Confidence Interval	() 95%; 29 to 54
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value is the percentage of the first 60 participants who had stable disease at Week 12, as assessed by the investigator.

3. Secondary Outcome

Title	Duration of Response
Description	Using RECIST criteria: date of first confirmed tumor response (CR or PR) to date of tumor progression or to death. Participants who did not progress or die were censored at their last radiologic assessment. Only participants who had a response were analyzed.
Time Frame	First response until progression of disease (up to 2.40 years). Assessments occurred at Week 12 and every 8 weeks thereafter.

Outcome Measure Data

Analysis Population Description

All participants in the Enrolled Population who had a CR or PR

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 milligrams (mg) (tablets) administered orally once a day
Measure Participants	78
Median (95% Confidence Interval) [weeks]	68

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free Survival is defined as the interval between the first day of treatment and the earliest date of disease progression or death due to any cause, whichever occurred first. Progressive disease is defined as a >=20% increase in target lesions.
Time Frame	From the first day of treatment to the earliest date of disease progression or death due to any cause (up to 2.40 years)

Outcome Measure Data

Analysis Population Description

All Enrolled Population. Participants who did not progress or die were censored at their last radiologic assessment.

Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 mg (tablets) administered orally once a day
Measure Participants	225
Median (95% Confidence Interval) [weeks]	45.3

Adverse Events

Time Frame	Until participant was off study, approximately 7.84 years
Arm/Group Title	Pazopanib 800 mg
Arm/Group Description	Pazopanib 800 milligrams (mg) (tablets) administered orally once a day
All Cause Mortality
	Pazopanib 800 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pazopanib 800 mg
	Affected / at Risk (%)	# Events
Total	80/225 (35.6%)
Blood and lymphatic system disorders
Anaemia	1/225 (0.4%)
Thrombocytopenia	1/225 (0.4%)
Cardiac disorders
Atrial fibrillation	2/225 (0.9%)
Myocardial infarction	2/225 (0.9%)
Stress cardiomyopathy	1/225 (0.4%)
Ventricular fibrillation	1/225 (0.4%)
Congenital, familial and genetic disorders
Hydrocele	1/225 (0.4%)
Eye disorders
Retinal tear	1/225 (0.4%)
Gastrointestinal disorders
Abdominal pain	3/225 (1.3%)
Diarrhhoea	2/225 (0.9%)
Gastrointestinal haemorrhage	3/225 (1.3%)
Large intestine perforation	2/225 (0.9%)
Vomiting	2/225 (0.9%)
Abdominal pain lower	1/225 (0.4%)
Abdominal pain upper	1/225 (0.4%)
Ascites	1/225 (0.4%)
Constipation	1/225 (0.4%)
Faecaloma	1/225 (0.4%)
Haemorrhoidal haemorrhage	1/225 (0.4%)
Ileal perforation	1/225 (0.4%)
Oesophagitis	1/225 (0.4%)
Pancreatitis	1/225 (0.4%)
Pancreatitis acute	1/225 (0.4%)
Small intestinal obstruction	1/225 (0.4%)
Large intestinal stenosis	1/225 (0.4%)
Large intestinal ulcer	1/225 (0.4%)
General disorders
Chest pain	4/225 (1.8%)
Fatigue	2/225 (0.9%)
General physical health deterioration	1/225 (0.4%)
Oedema peripheral	1/225 (0.4%)
Hepatobiliary disorders
Bile duct stenosis	1/225 (0.4%)
Bile duct stone	1/225 (0.4%)
Hepatic failure	1/225 (0.4%)
Drug-induced liver injury	1/225 (0.4%)
Jaundice	1/225 (0.4%)
Infections and infestations
Anal abscess	1/225 (0.4%)
Gastroenteritis	1/225 (0.4%)
Infection	1/225 (0.4%)
Lower respiratory tract infection	1/225 (0.4%)
Wound infection	1/225 (0.4%)
Cellulitis	1/225 (0.4%)
Injury, poisoning and procedural complications
Femur fracture	1/225 (0.4%)
Hip fracture	1/225 (0.4%)
Post procedural complication	1/225 (0.4%)
Postoperative wound complication	1/225 (0.4%)
Road traffic accident	1/225 (0.4%)
Stab wound	1/225 (0.4%)
Investigations
Alanine aminotransferase increased	3/225 (1.3%)
Aspartate aminotransferase increased	2/225 (0.9%)
Body temperature increased	1/225 (0.4%)
Gamma-glutamyltransferase increased	1/225 (0.4%)
Lipase increased	3/225 (1.3%)
Blood creatinine increased	1/225 (0.4%)
Blood thyroid stimulating hormone decreased	1/225 (0.4%)
Blood urea increased	1/225 (0.4%)
Ejection fraction decreased	1/225 (0.4%)
Metabolism and nutrition disorders
Dehydration	3/225 (1.3%)
Hyponatraemia	2/225 (0.9%)
Hypercalcaemia	1/225 (0.4%)
Hyperkalaemia	1/225 (0.4%)
Hypoglycaemia	1/225 (0.4%)
Decreased appetite	1/225 (0.4%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	2/225 (0.9%)
Arthritis	1/225 (0.4%)
Back pain	1/225 (0.4%)
Muscular weakness	1/225 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/225 (0.4%)
Haemangioblastoma	1/225 (0.4%)
Colorectal adenocarcinoma	1/225 (0.4%)
Nervous system disorders
Transient ischaemic attack	2/225 (0.9%)
Cerebrovascular accident	1/225 (0.4%)
Dizziness	1/225 (0.4%)
Haemorrhage intracranial	1/225 (0.4%)
Nerve root compression	1/225 (0.4%)
Headache	1/225 (0.4%)
Psychiatric disorders
Confusional state	2/225 (0.9%)
Depression	1/225 (0.4%)
Renal and urinary disorders
Renal failure acute	1/225 (0.4%)
Haematuria	1/225 (0.4%)
Proteinuria	1/225 (0.4%)
Urogenital haemorrhage	1/225 (0.4%)
Reproductive system and breast disorders
Pelvic pain	1/225 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	6/225 (2.7%)
Pulmonary embolism	5/225 (2.2%)
Dyspnoea	3/225 (1.3%)
Pneumothorax	2/225 (0.9%)
Haemoptysis	1/225 (0.4%)
Skin and subcutaneous tissue disorders
Skin lesion	1/225 (0.4%)
Vascular disorders
Hypertension	2/225 (0.9%)
Deep vein thrombosis	1/225 (0.4%)
Haematoma	1/225 (0.4%)
Other (Not Including Serious) Adverse Events
	Pazopanib 800 mg
	Affected / at Risk (%)	# Events
Total	215/225 (95.6%)
Blood and lymphatic system disorders
Anaemia	12/225 (5.3%)
Gastrointestinal disorders
Diarrhoea	148/225 (65.8%)
Nausea	99/225 (44%)
Vomiting	50/225 (22.2%)
Abdominal pain	37/225 (16.4%)
Constipation	37/225 (16.4%)
Dyspepsia	25/225 (11.1%)
Flatulence	14/225 (6.2%)
Abdominal pain upper	13/225 (5.8%)
Stomatitis	13/225 (5.8%)
Abdominal distension	12/225 (5.3%)
General disorders
Fatigue	108/225 (48%)
Oedema peripheral	20/225 (8.9%)
Chest pain	16/225 (7.1%)
Pyrexia	16/225 (7.1%)
Asthenia	14/225 (6.2%)
Mucosal inflammation	12/225 (5.3%)
Infections and infestations
Upper respiratory tract infection	22/225 (9.8%)
Nasopharyngitis	18/225 (8%)
Investigations
Alanine aminotransferase increased	32/225 (14.2%)
Aspartate aminotransferase increased	28/225 (12.4%)
Weight decreased	23/225 (10.2%)
Metabolism and nutrition disorders
Decreased appetite	69/225 (30.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	35/225 (15.6%)
Back pain	28/225 (12.4%)
Musculoskeletal chest pain	12/225 (5.3%)
Muscle spasms	19/225 (8.4%)
Pain in extremity	20/225 (8.9%)
Myalgia	12/225 (5.3%)
Nervous system disorders
Dysgeusia	57/225 (25.3%)
Headache	47/225 (20.9%)
Dizziness	31/225 (13.8%)
Psychiatric disorders
Insomnia	21/225 (9.3%)
Anxiety	13/225 (5.8%)
Respiratory, thoracic and mediastinal disorders
Cough	44/225 (19.6%)
Dyspnoea	26/225 (11.6%)
Epistaxis	25/225 (11.1%)
Dysphonia	12/225 (5.3%)
Oropharyngeal pain	15/225 (6.7%)
Skin and subcutaneous tissue disorders
Hair colour changes	100/225 (44.4%)
Rash	37/225 (16.4%)
Palmar-plantar erythrodysaesthesia syndrome	25/225 (11.1%)
Alopecia	26/225 (11.6%)
Skin hypopigmentation	14/225 (6.2%)
Dry skin	14/225 (6.2%)
Erythema	12/225 (5.3%)
Vascular disorders
Hypertension	99/225 (44%)

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.