Efficacy and Safety of Pazopanib Monotherapy After First-line Chemotherapy in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Asian Women

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01227928
• Collaborator: (none)
• Enrollment: 145
• Locations: 15
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a study to determine whether therapy with pazopanib is effective and safe in Asian women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose cancer has not progressed on first-line chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Ovarian	Drug: Pazopanib; Drug: Placebo comparator	Phase 2

Detailed Description

This study is an extension study to the VEG110655 study. The parent study, VEG110655, was designed to evaluate whether pazopanib 800 mg daily for 52 weeks will prolong progression free survival (PFS) in women diagnosed with ovarian, fallopian tube or primary peritoneal cancer. These women will have obtained stable disease, a complete remission, or a partial remission after debulking surgery and at least five cycles of chemotherapy (taxane/platinum). This extension study will evaluate safety and efficacy outcomes of pazopanib monotherapy and placebo in an Asian population with the same indication as the parent study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 145 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Study to Evaluate Efficacy and Safety of Pazopanib Monotherapy in Asian Women Who Have Not Progressed After First-line Chemotherapy for Advanced Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma - An Extension Study to VEG110655
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pazopanib experimental medication	Drug: Pazopanib; Pazopanib 800 mg daily for 24 months
Placebo Comparator: placebo placebo comparator	Drug: Placebo comparator; Placebo 800 mg daily for 24 months

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [From randomization until evidence of progressive disease or death, whichever occurred first (average of 15.2 months)]

   PFS is defined as the time interval between randomization and evidence of progressive disease (PD), as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death, whichever occurred first. A visit-based analysis approach to determine participants' dates of progression was applied in the analysis method. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Participants who were alive and had not progressed at the time of analysis were censored at the date associated with the last visit with adequate assessment.

Secondary Outcome Measures

1. Overall Survival [From randomization until death due to any cause (average of 29.4 months)]

   Overall survival is defined as the time interval from the date of randomization to the date of death due to any cause.

2. PFS by Gynaecologic Cancer Intergroup (GCIG) Criteria [From randomization to the earliest date of disease progression per GCIG criteria or death due to any cause (average of 15.2 months)]

   PFS by GCIG criteria is defined as the time from the randomization date to the earliest date of disease progression (PD) per GCIG criteria or death due to any cause. Per GCIG criteria, an objective progression is defined as the earliest event of either tumor progression based on RECIST v1.0 or confirmed CA-125 progression. A participant is counted as "Progressed per RECIST" if the radiological PD per RECIST occurred prior to or on the same day as CA-125 progression. A participant is counted as "Progressed per CA-125" if the radiological PD occurred after CA-125 progression. Per RECIST, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Participants who were alive and had not progressed at the time of analysis were censored at the date associated with the last visit with adequate assessment.

3. Number of Participants With Any Dose Reduction or Any Dose Interruption [From Week 1 until the end of the treatment period (up to Study Week 108)]

   Dose interruptions or reductions may have been required following potential drug-related toxicities. As a general rule, if dose reduction of investigational product (IP) was necessary, the dose should have been reduced stepwise by 200 mg at each step, and the participant should have been monitored for 10 to 14 days. If toxicity recurred or worsened during this monitoring time, the IP could have been interrupted and/or the dose of IP further decreased, with continued monitoring for an additional 10 to 14 days, and so on. The cut off for these data was October 12, 2012.

4. Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious Adverse Event (SAE) [From Week 1 until the end of the treatment period (up to Study Week 108)]

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalizaton or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. See the non-serious AE/SAE module for a list of specific events.

5. Number of Participants With Any On-therapy AE and Any AE Related to Study Treatment [From Week 1 until the end of the treatment period (up to Study Week 108)]

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. On-therapy AEs were those reported from the first day that randomized study drug was received to 28 days after the last dose of randomized study drug, and within 28 days of dose interruption. Relatedness was assessed by the Investigator.

6. Number of Participants With Any Grade 3 or 4 AE [From Week 1 until the end of the treatment period (up to Study Week 108)]

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0 was used to grade AEs per the following scale to assess severity: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling AE; Grade 5, death related to AE.

7. Number of Participants With the Indicated On-therapy Grade 3-5 AEs [From Week 1 until the end of the treatment period (up to Study Week 108)]

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. On-therapy AEs were those reported from the first day that randomized study drug was received to 28 days after the last dose of randomized study drug, and within 28 days of dose interruption. The NCI-CTCAE Version 3.0 was used to grade AEs per the following scale to assess severity: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling AE; Grade 5, death related to AE. ALT=alanine aminotransferase; AST=aspartate aminotransferase.

8. Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment, Dose Interruption, and Dose Reduction [From Week 1 until the end of the treatment period (up to Study Week 108)]

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Dose interruptions or reductions may have been required following potential drug-related toxicities. As a general rule, if dose reduction of investigational product (IP) was necessary, the dose should have been reduced stepwise by 200 mg at each step, and the participant should have been monitored for 10 to 14 days. If toxicity recurred or worsened during this monitoring time, the IP could have been interrupted and/or the dose of IP further decreased, with continued monitoring for an additional 10 to 14 days, and so on.

9. Number of Participants With Any SAE, Any SAE Related to Study Treatment, and Any Fatal SAE [From Week 1 until the end of the treatment period (up to Study Week 108)]

   An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalizaton or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. See the non-serious AE/SAE module for a list of specific events. Relatedness was assessed by the Investigator.

10. Number of Participants With the Indicated Worst-case On-therapy Blood Pressure Shifts From Baseline [From Week 1 until the end of the treatment period (up to Study Week 108)]

    Systolic blood pressure (SBP) and Diatolic blood pressure (DBP) are measured in millimeters of mercury (mmHg). A participant could have been counted in more than one shift category. Participants who experienced shifts in both SBP and DBP are represented under each individual parameter. A worst-case on-therapy shift is defined as the worst shift that occurred at any time during the treatment period.

11. Number of Participants With the Indicated Worst-case On-therapy Shift From Baseline in Bazett's Corrected QT Interval (QTc) [From Week 1 until the end of the treatment period (up to Study Week 108)]

    12-lead ECGs were obtained at the scheduled visits. A worst-case on-therapy shift is defined as the worst shift that occurred at any time during the treatment period. The QTc is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the faster the heart rate the shorter the QTc. If a QTc >=500 milliseconds (msec) was noted on a scheduled or unscheduled electrocardiogram (ECG), then two additional ECGs should have been obtained within 5 minutes to confirm the abnormality. The average QTc was determined from the three ECG tracings by manual evaluation and was used to determine continued eligibility.

12. Number of Participants With the Indicated Worst-case On-therapy Hematology Parameter Grade Shifts From Baseline Grade [From Week 1 until the end of the treatment period (up to Study Week 108)]

    Grade shifts from Baseline were assessed as any grade increase (AGI), increase to Grade (G) 3 (ITG3), and increase to Grade 4 (ITG4). Toxicities were graded according to the National Cancer Institute common toxicity criteria (NCI-Common Toxicity Criteria for Adverse Events), version 4.0. Grade refers to the severity of the toxicity. The CTCAE displays Grades (G) 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: G1, mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; G2, moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); G3, severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; G4, Life-threatening consequences; urgent intervention indicated.; G5, death related to AE.

13. Number of Participants With the Indicated Worst-case On-therapy Chemistry Parameter Grade Shifts From Baseline Grade [From Week 1 until the end of the treatment period (up to Study Week 108)]

    Grade shifts from Baseline were assessed as any grade increase (AGI), increase to Grade (G) 3 (ITG3), and increase to Grade 4 (ITG4). Toxicities were graded according to the National Cancer Institute common toxicity criteria (NCI-Common Toxicity Criteria for Adverse Events), version 4.0. Grade refers to the severity of the toxicity. The CTCAE displays Grades (G) 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: G1, mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; G2, moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); G3, severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; G4, Life-threatening consequences; urgent intervention indicated.; G5, death related to AE.

14. Number of Participants With the Indicated Worst-case Eastern Cooperative Oncology Group (ECOG) Performance Status Shifts From Baseline Grades of 0, 1, and 2 [From Week 1 until the end of the treatment period (up to Study Week 108)]

    The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• written informed consent

• At least 18 years old.

• Histologically confirmed, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma that was treated with surgical debulking and at least five cycles of platinum-taxane doublet chemotherapy.

• Study randomization at least 3 weeks and not more than 12 weeks from the date of the last chemotherapy dose, and all major toxicities from the previous chemotherapy must have resolved.

• No evidence of disease progression

• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2

• Able to swallow and retain oral medication.

• Adequate hematologic, hepatic, and renal system function as follows:

Hematologic

• Absolute neutrophil count (ANC) at least 1.5 X 10^9/L

• Hemoglobin at least 9 g/dL (or 5.59 mmol/L)

• Platelets at least 100 X 10^9/L

• Prothrombin time (PT) or international normalized ratio (INR) up to 1.2 X ULN

• Activated partial thromboplastin time (aPTT) up to 1.2 X ULN Hepatic

• Total bilirubin up to 1.5 X ULN

• AST and ALT up to 2.5 X ULN Renal

• Serum creatinine up to 1.5 mg/dL

Or, if greater than 1.5 mg/dL:

Calculated creatinine clearance at least 50 mL/min Urine Protein

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

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception.

Exclusion Criteria:

• Either (a) bulky disease, or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy

• Synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless certain conditions are met.

• Clinically significant gastrointestinal abnormalities

• Prolongation of corrected QT interval (QTc) > 480 msecs

• History of any one or more cardiovascular conditions within the past 6 months prior to randomization

• Poorly controlled hypertension

• History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization

• Major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.

• Evidence of active bleeding or bleeding diathesis.

• Hemoptysis within 6 weeks prior to randomization.

• Endobronchial metastases.

• Serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

• Investigational or anti-VEGF anticancer therapy prior to study randomization.

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.

• Prior or concurrent invasive malignancies that currently or within the last 5 years show/ed activity of disease (except ovarian, fallopian tube, or peritoneal cancer, or concurrent endometrial cancer FIGO stages IA/B)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Guangzhou	Guangdong	China
2	GSK Investigational Site	Nanjing	Jiangsu	China	210009
3	GSK Investigational Site	Shenyang	Liaoning	China	110022
4	GSK Investigational Site	Jinan	Shandong	China	250012
5	GSK Investigational Site	Chengdu	Sichuan	China	610041
6	GSK Investigational Site	Hangzhou	Zhejiang	China	310006
7	GSK Investigational Site	Hangzhou	Zhejiang	China	310022
8	GSK Investigational Site	Beijing		China	100021
9	GSK Investigational Site	Beijing		China	100044
10	GSK Investigational Site	Beijing		China	100853
11	GSK Investigational Site	Shanghai		China	200032
12	GSK Investigational Site	Hong Kong		Hong Kong
13	GSK Investigational Site	Seoul		Korea, Republic of	135-710
14	GSK Investigational Site	Taipei		Taiwan	104
15	GSK Investigational Site	Taipei		Taiwan	112

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01227928
• Other Study ID Numbers: 114012
• First Posted: Oct 25, 2010
• Last Update Posted: Mar 3, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by GlaxoSmithKline: tyrosine kinase inhibitors; Primary Peritoneal Carcinoma; primary peritoneal cancer; ovarian cancer; Fallopian Tube Cancer; gynecologic cancer; anti-angiogenesis; pazopanib
• Additional relevant MeSH terms: Ovarian Neoplasms

Study Results

Participant Flow

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Period Title: Overall Study
STARTED	72	73
COMPLETED	50	56
NOT COMPLETED	22	17

Baseline Characteristics

Arm/Group Title	Placebo	Pazopanib 800 Milligrams	Total
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.	Total of all reporting groups
Overall Participants	72	73	145
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.1 (10.46)	51.7 (9.62)	52.9 (10.09)
Sex: Female, Male (Count of Participants)
Female	72 100%	73 100%	145 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Asian	72 100%	73 100%	145 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined as the time interval between randomization and evidence of progressive disease (PD), as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death, whichever occurred first. A visit-based analysis approach to determine participants' dates of progression was applied in the analysis method. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Participants who were alive and had not progressed at the time of analysis were censored at the date associated with the last visit with adequate assessment.
Time Frame	From randomization until evidence of progressive disease or death, whichever occurred first (average of 15.2 months)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants who were not screen failures. Participants who were screen failures and randomized by mistake, but who did not receive study treatment, were not included. The treatment assignment in the ITT Population was based on the randomized treatment. The data cut off was October 12, 2012.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	73
Median (95% Confidence Interval) [months]	18.1	18.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib 800 Milligrams
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.984
	Confidence Interval	(2-Sided) 95%; 0.595 to 1.626
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Hazard Ratio (HR) is estimated using a Pike estimator. The HR was adjusted for the stratification factor of first-line treatment outcome.

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time interval from the date of randomization to the date of death due to any cause.
Time Frame	From randomization until death due to any cause (average of 29.4 months)

Outcome Measure Data

Analysis Population Description

ITT Population. Participants who were alive as of study completion were censored at the last contact date. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	73
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib 800 Milligrams
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5901
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.811
	Confidence Interval	(2-Sided) 95%; 0.376 to 1.751
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Hazard Ratio (HR) is estimated using a Pike estimator. The HR was adjusted for the three stratification factors.

3. Secondary Outcome

Title	PFS by Gynaecologic Cancer Intergroup (GCIG) Criteria
Description	PFS by GCIG criteria is defined as the time from the randomization date to the earliest date of disease progression (PD) per GCIG criteria or death due to any cause. Per GCIG criteria, an objective progression is defined as the earliest event of either tumor progression based on RECIST v1.0 or confirmed CA-125 progression. A participant is counted as "Progressed per RECIST" if the radiological PD per RECIST occurred prior to or on the same day as CA-125 progression. A participant is counted as "Progressed per CA-125" if the radiological PD occurred after CA-125 progression. Per RECIST, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Participants who were alive and had not progressed at the time of analysis were censored at the date associated with the last visit with adequate assessment.
Time Frame	From randomization to the earliest date of disease progression per GCIG criteria or death due to any cause (average of 15.2 months)

Outcome Measure Data

Analysis Population Description

ITT Population. The cut off for these data was October 12, 2012.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	73
Median (95% Confidence Interval) [months]	15.2	16.1

4. Secondary Outcome

Title	Number of Participants With Any Dose Reduction or Any Dose Interruption
Description	Dose interruptions or reductions may have been required following potential drug-related toxicities. As a general rule, if dose reduction of investigational product (IP) was necessary, the dose should have been reduced stepwise by 200 mg at each step, and the participant should have been monitored for 10 to 14 days. If toxicity recurred or worsened during this monitoring time, the IP could have been interrupted and/or the dose of IP further decreased, with continued monitoring for an additional 10 to 14 days, and so on. The cut off for these data was October 12, 2012.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Any Reduction	26 36.1%	64 87.7%
Any Interruption	44 61.1%	65 89%

5. Secondary Outcome

Title	Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious Adverse Event (SAE)
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalizaton or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. See the non-serious AE/SAE module for a list of specific events.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Any AE	65 90.3%	72 98.6%
Any SAE	4 5.6%	7 9.6%

6. Secondary Outcome

Title	Number of Participants With Any On-therapy AE and Any AE Related to Study Treatment
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. On-therapy AEs were those reported from the first day that randomized study drug was received to 28 days after the last dose of randomized study drug, and within 28 days of dose interruption. Relatedness was assessed by the Investigator.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Any on-therapy AE	65 90.3%	72 98.6%
Any AE related to study treatment	52 72.2%	71 97.3%

7. Secondary Outcome

Title	Number of Participants With Any Grade 3 or 4 AE
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0 was used to grade AEs per the following scale to assess severity: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling AE; Grade 5, death related to AE.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Number [participants]	8 11.1%	39 53.4%

8. Secondary Outcome

Title	Number of Participants With the Indicated On-therapy Grade 3-5 AEs
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. On-therapy AEs were those reported from the first day that randomized study drug was received to 28 days after the last dose of randomized study drug, and within 28 days of dose interruption. The NCI-CTCAE Version 3.0 was used to grade AEs per the following scale to assess severity: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling AE; Grade 5, death related to AE. ALT=alanine aminotransferase; AST=aspartate aminotransferase.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Hypertension, Grade 3	1 1.4%	13 17.8%
Neutropenia, Grade 3	0 0%	9 12.3%
Leukopenia, Grade 3	0 0%	1 1.4%
Diarrhea, Grade 3	1 1.4%	5 6.8%
ALT increased, Grade 3	0 0%	1 1.4%
Thrombocytopenia, Grade 3	0 0%	3 4.1%
AST increased, Grade 3	0 0%	1 1.4%
Neutrophil count decreased, Grade 3	0 0%	2 2.7%
Neutrophil count decreased, Grade 4	0 0%	1 1.4%
Arthralgia, Grade 3	0 0%	1 1.4%
Upper respiratory tract infection, Grade 3	1 1.4%	0 0%
Protein urine, Grade 3	0 0%	1 1.4%
Proteinuria, Grade 3	0 0%	1 1.4%
Bone pain, Grade 3	0 0%	1 1.4%
Toothache, Grade 3	0 0%	1 1.4%
Pyrexia, Grade 3	1 1.4%	0 0%
Hepatic function abnormal, Grade 3	0 0%	1 1.4%
Liver injury, Grade 3	0 0%	1 1.4%
Abdominal distension, Grade 3	1 1.4%	0 0%
Bradycardia, Grade 3	0 0%	1 1.4%
Febrile neutropenia, Grade 3	0 0%	1 1.4%
Thrombus in device, Grade 3	0 0%	1 1.4%
Pruritis, Grade 3	1 1.4%	0 0%
Amylase increased, Grade 3	1 1.4%	0 0%
Cerebral ischaemia, Grade 3	1 1.4%	0 0%
Foot fracture, Grade 3	1 1.4%	0 0%

9. Secondary Outcome

Title	Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment, Dose Interruption, and Dose Reduction
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Dose interruptions or reductions may have been required following potential drug-related toxicities. As a general rule, if dose reduction of investigational product (IP) was necessary, the dose should have been reduced stepwise by 200 mg at each step, and the participant should have been monitored for 10 to 14 days. If toxicity recurred or worsened during this monitoring time, the IP could have been interrupted and/or the dose of IP further decreased, with continued monitoring for an additional 10 to 14 days, and so on.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Permanent discontinuation	1 1.4%	18 24.7%
Dose interruption	29 40.3%	67 91.8%
Dose reduction	24 33.3%	63 86.3%

10. Secondary Outcome

Title	Number of Participants With Any SAE, Any SAE Related to Study Treatment, and Any Fatal SAE
Description	An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalizaton or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. See the non-serious AE/SAE module for a list of specific events. Relatedness was assessed by the Investigator.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population: all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Any SAE	4 5.6%	7 9.6%
Any SAE related to study treatment	1 1.4%	4 5.5%
Any fatal SAE	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Blood Pressure Shifts From Baseline
Description	Systolic blood pressure (SBP) and Diatolic blood pressure (DBP) are measured in millimeters of mercury (mmHg). A participant could have been counted in more than one shift category. Participants who experienced shifts in both SBP and DBP are represented under each individual parameter. A worst-case on-therapy shift is defined as the worst shift that occurred at any time during the treatment period.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population. One participant on placebo did not report any blood pressure measurements post-Baseline. The cut off for these data was January 10, 2014.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	71	72
SBP, Any increase to >=120 mmHg	28 38.9%	53 72.6%
SBP, Increase to 140-<160 mmHg	4 5.6%	23 31.5%
SBP, Increase to >=160 mmHg	0 0%	6 8.2%
DBP, Any increase to >=80 mmHg	35 48.6%	59 80.8%
DBP, Increase to 90-<100 mmHg	1 1.4%	25 34.2%
DBP, Increase to >=100 mmHg	0 0%	5 6.8%

12. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Shift From Baseline in Bazett's Corrected QT Interval (QTc)
Description	12-lead ECGs were obtained at the scheduled visits. A worst-case on-therapy shift is defined as the worst shift that occurred at any time during the treatment period. The QTc is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the faster the heart rate the shorter the QTc. If a QTc >=500 milliseconds (msec) was noted on a scheduled or unscheduled electrocardiogram (ECG), then two additional ECGs should have been obtained within 5 minutes to confirm the abnormality. The average QTc was determined from the three ECG tracings by manual evaluation and was used to determine continued eligibility.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population. Only those participants for which a post-Baseline ECG was conducted were analyzed. The cut off for these data was October 12, 2012.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	69	70
Any increase to >=450 msec	10 13.9%	5 6.8%
Increase to 481-500 msec	1 1.4%	1 1.4%
Increase to >=501 msec	2 2.8%	0 0%

13. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Hematology Parameter Grade Shifts From Baseline Grade
Description	Grade shifts from Baseline were assessed as any grade increase (AGI), increase to Grade (G) 3 (ITG3), and increase to Grade 4 (ITG4). Toxicities were graded according to the National Cancer Institute common toxicity criteria (NCI-Common Toxicity Criteria for Adverse Events), version 4.0. Grade refers to the severity of the toxicity. The CTCAE displays Grades (G) 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: G1, mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; G2, moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); G3, severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; G4, Life-threatening consequences; urgent intervention indicated.; G5, death related to AE.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population. Data are presented for only those participants with laboratory values. The cut off for these data was October 12, 2012.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	69	71
Hemoglobin, AGI	4 5.6%	14 19.2%
Hemoglobin, ITG3	0 0%	0 0%
Hemoglobin, ITG4	0 0%	0 0%
Lymphocytes, AGI	11 15.3%	9 12.3%
Lymphocytes, ITG3	2 2.8%	1 1.4%
Lymphocytes, ITG4	0 0%	0 0%
Neutrophils, AGI	22 30.6%	55 75.3%
Neutrophils, ITG3	0 0%	11 15.1%
Neutrophils, ITG4	0 0%	2 2.7%
Platelets, AGI	10 13.9%	32 43.8%
Platelets, ITG3	0 0%	1 1.4%
Platelets, ITG4	0 0%	0 0%
White blood cells, AGI	19 26.4%	48 65.8%
White blood cells, ITG3	0 0%	2 2.7%
White blood cells, ITG4	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case On-therapy Chemistry Parameter Grade Shifts From Baseline Grade
Description	Grade shifts from Baseline were assessed as any grade increase (AGI), increase to Grade (G) 3 (ITG3), and increase to Grade 4 (ITG4). Toxicities were graded according to the National Cancer Institute common toxicity criteria (NCI-Common Toxicity Criteria for Adverse Events), version 4.0. Grade refers to the severity of the toxicity. The CTCAE displays Grades (G) 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: G1, mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; G2, moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); G3, severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; G4, Life-threatening consequences; urgent intervention indicated.; G5, death related to AE.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population. Data are presented for only those participants with laboratory values. The cut off for these data was October 12, 2012.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	69	70
Albumin, AGI, n=69, 70	2 2.8%	1 1.4%
Albumin, ITG3, n=69, 70	0 0%	0 0%
Albumin, ITG4, n=69, 70	0 0%	0 0%
Creatinine, AGI, n=69, 70	2 2.8%	2 2.7%
Creatinine, ITG3, n=69, 70	0 0%	1 1.4%
Creatinine, ITG4, n=69, 70	0 0%	0 0%
Hypercalcemia, AGI, n=69, 69	9 12.5%	3 4.1%
Hypercalcemia, ITG3, n=69, 69	1 1.4%	0 0%
Hypercalcemia, ITG4, n=69, 69	0 0%	0 0%
Hyperglycemia, AGI, n=69, 70	16 22.2%	14 19.2%
Hyperglycemia, ITG3, n=69, 70	0 0%	0 0%
Hyperglycemia, ITG4, n=69, 70	0 0%	0 0%
Hyperkalemia, AGI, n=69, 70	0 0%	1 1.4%
Hyperkalemia, ITG3, n=69, 70	0 0%	0 0%
Hyperkalemia, ITG4, n=69, 70	0 0%	0 0%
Hypermagnesemia, AGI, n=69, 69	6 8.3%	2 2.7%
Hypermagnesemia, ITG3, n=69, 69	1 1.4%	1 1.4%
Hypermagnesemia, ITG4, n=69, 69	0 0%	0 0%
Hypernatremia, AGI, n=69, 70	2 2.8%	3 4.1%
Hypernatremia, ITG3, n=69, 70	0 0%	0 0%
Hypernatremia, ITG4, n=69, 70	0 0%	0 0%
Hypocalcemia, AGI, n=69, 69	4 5.6%	5 6.8%
Hypocalcemia, ITG3, n=69, 69	0 0%	0 0%
Hypocalcemia, ITG4, n=69, 69	0 0%	0 0%
Hypoglycemia, AGI, n=69, 70	0 0%	3 4.1%
Hypoglycemia, ITG3, n=69, 70	0 0%	0 0%
Hypoglycemia, ITG4, n=69, 70	0 0%	0 0%
Hypokalemia, AGI, n=69, 70	10 13.9%	6 8.2%
Hypokalemia, ITG3, n=69, 70	0 0%	0 0%
Hypokalemia, ITG4, n=69, 70	0 0%	0 0%
Hypomagnesemia, AGI, n=69, 69	6 8.3%	2 2.7%
Hypomagnesemia, ITG3, n=69, 69	0 0%	0 0%
Hypomagnesemia, ITG4, n=69, 69	0 0%	0 0%
Hyponatremia, AGI, n=69, 70	1 1.4%	1 1.4%
Hyponatremia, ITG3, n=69, 70	0 0%	0 0%
Hyponatremia, ITG4, n=69, 70	0 0%	0 0%
Phosphate, AGI, n=69, 69	2 2.8%	4 5.5%
Phosphate, ITG3, n=69, 69	0 0%	0 0%
Phosphate, ITG4, n=69, 69	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case Eastern Cooperative Oncology Group (ECOG) Performance Status Shifts From Baseline Grades of 0, 1, and 2
Description	The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead.
Time Frame	From Week 1 until the end of the treatment period (up to Study Week 108)

Outcome Measure Data

Analysis Population Description

All Treated Population. The cut off for these data was October 12, 2012.

Arm/Group Title	Placebo	Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.	Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
Measure Participants	72	72
Baseline score of 0; shift to 0	56 77.8%	46 63%
Baseline score of 0; shift to 1	2 2.8%	13 17.8%
Baseline score of 0; shift to 2	0 0%	0 0%
Baseline score of 1; shift to 0	0 0%	0 0%
Baseline score of 1; shift to 1	12 16.7%	13 17.8%
Baseline score of 1; shift to 2	1 1.4%	0 0%
Baseline score of 2; shift to 0	0 0%	0 0%
Baseline score of 2; shift to 1	0 0%	0 0%
Baseline score of 2; shift to 2	1 1.4%	0 0%

Adverse Events

Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Treated Population, comprised of all randomized participants who received at least one dose of investigational product. Treatment assignments in the All Treated Population were based on the actual treatment received, if different from the randomized treatment.
Arm/Group Title	Placebo		Pazopanib 800 Milligrams
Arm/Group Description	Participants received matching placebo administered orally once daily for up to 24 months.		Participants received pazopanib 800 milligrams administered orally once daily for up to 24 months.
All Cause Mortality
	Placebo		Pazopanib 800 Milligrams
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Pazopanib 800 Milligrams
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/72 (5.6%)		7/72 (9.7%)
Blood and lymphatic system disorders
Febrile neutropenia	0/72 (0%)		1/72 (1.4%)
Gastrointestinal disorders
Ileus paralytic	0/72 (0%)		1/72 (1.4%)
Salivary gland calculus	0/72 (0%)		1/72 (1.4%)
General disorders
Thrombosis in device	0/72 (0%)		1/72 (1.4%)
Hepatobiliary disorders
Hepatic function abnormal	0/72 (0%)		1/72 (1.4%)
Liver injury	0/72 (0%)		1/72 (1.4%)
Infections and infestations
Urinary tract infection	1/72 (1.4%)		0/72 (0%)
Injury, poisoning and procedural complications
Foot fracture	1/72 (1.4%)		0/72 (0%)
Investigations
Alanine aminotransferase increased	0/72 (0%)		1/72 (1.4%)
Aspartate aminotransferase increased	0/72 (0%)		1/72 (1.4%)
Neutrophil count decreased	0/72 (0%)		1/72 (1.4%)
Nervous system disorders
Cerebral artery stenosis	1/72 (1.4%)		0/72 (0%)
Cerebral ischaemia	1/72 (1.4%)		0/72 (0%)
Vascular disorders
Hypertension	1/72 (1.4%)		0/72 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Pazopanib 800 Milligrams
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/72 (81.9%)		72/72 (100%)
Blood and lymphatic system disorders
Neutropenia	16/72 (22.2%)		46/72 (63.9%)
Leukopenia	18/72 (25%)		39/72 (54.2%)
Thrombocytopenia	4/72 (5.6%)		17/72 (23.6%)
Gastrointestinal disorders
Diarrhoea	5/72 (6.9%)		35/72 (48.6%)
Abdominal pain	5/72 (6.9%)		11/72 (15.3%)
Nausea	3/72 (4.2%)		11/72 (15.3%)
Abdominal pain upper	2/72 (2.8%)		9/72 (12.5%)
Dyspepsia	5/72 (6.9%)		3/72 (4.2%)
Abdominal discomfort	4/72 (5.6%)		2/72 (2.8%)
Abdominal distension	4/72 (5.6%)		2/72 (2.8%)
General disorders
Fatigue	8/72 (11.1%)		14/72 (19.4%)
Chest discomfort	3/72 (4.2%)		4/72 (5.6%)
Pyrexia	4/72 (5.6%)		3/72 (4.2%)
Infections and infestations
Nasopharyngitis	9/72 (12.5%)		9/72 (12.5%)
Upper respiratory tract infection	5/72 (6.9%)		6/72 (8.3%)
Urinary tract infection	6/72 (8.3%)		5/72 (6.9%)
Investigations
Alanine aminotransferase increased	4/72 (5.6%)		19/72 (26.4%)
Aspartate aminotransferase increased	6/72 (8.3%)		16/72 (22.2%)
Blood thyroid stimulating hormone increased	2/72 (2.8%)		15/72 (20.8%)
Blood lactate dehydrogenase increased	2/72 (2.8%)		7/72 (9.7%)
Neutrophil count decreased	2/72 (2.8%)		6/72 (8.3%)
Blood bilirubin increased	1/72 (1.4%)		5/72 (6.9%)
Protein urine present	1/72 (1.4%)		6/72 (8.3%)
Electrocardiogram QT prolonged	4/72 (5.6%)		0/72 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/72 (1.4%)		8/72 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/72 (5.6%)		7/72 (9.7%)
Pain in extremity	3/72 (4.2%)		4/72 (5.6%)
Back pain	2/72 (2.8%)		5/72 (6.9%)
Myalgia	5/72 (6.9%)		2/72 (2.8%)
Nervous system disorders
Headache	5/72 (6.9%)		13/72 (18.1%)
Dizziness	3/72 (4.2%)		10/72 (13.9%)
Psychiatric disorders
Insomnia	5/72 (6.9%)		2/72 (2.8%)
Renal and urinary disorders
Proteinuria	0/72 (0%)		4/72 (5.6%)
Skin and subcutaneous tissue disorders
Hair colour changes	1/72 (1.4%)		29/72 (40.3%)
Palmar-plantar erythrodysaesthesia syndrome	2/72 (2.8%)		21/72 (29.2%)
Rash	8/72 (11.1%)		4/72 (5.6%)
Vascular disorders
Hypertension	20/72 (27.8%)		55/72 (76.4%)

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.