Efficacy and Safety of Pazopanib Monotherapy After First Line Chemotherapy in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• ClinicalTrials.gov Identifier: NCT00866697
• Recruitment Status: Completed
• First Posted: March 20, 2009
• Results First Posted: December 19, 2013
• Last Update Posted: February 16, 2021
• Sponsor: Novartis Pharmaceuticals
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ovarian Cancer
• Interventions: Drug: Pazopanib; Drug: Placebo
• Enrollment: 940

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Period Title: Overall Study
Started	468	472
Completed [1]	254	244
Not Completed	214	228
Reason Not Completed
Study closed/terminated	156	138
Lost to Follow-up	22	28
Physician Decision	3	5
Withdrawal by Subject	33	57
[1] Death

Baseline Characteristics

Arm/Group Title		Placebo	Pazopanib 800 mg	Total
Arm/Group Description		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.	Total of all reporting groups
Overall Number of Baseline Participants		468	472	940
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	468 participants	472 participants	940 participants
		56.8 (10.83)	55.8 (10.54)	56.3 (10.69)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	468 participants	472 participants	940 participants
	Female	468 100.0%	472 100.0%	940 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	468 participants	472 participants	940 participants
	African American/African Heritage	1 0.2%	2 0.4%	3 0.3%
	American Indian or Alaska Native	1 0.2%	1 0.2%	2 0.2%
	Central/South Asian Heritage (Her)	1 0.2%	0 0.0%	1 0.1%
	Japanese/East Asian Her/South East Asian Her	102 21.8%	106 22.5%	208 22.1%
	White	363 77.6%	363 76.9%	726 77.2%

Outcome Measures

1. Primary Outcome

Title	Investigator-assessed Progression-free Survival (PFS)
Description	PFS is the interval between the date of randomization and the date of progression, defined by Response Evaluation Criteria in Solid Tumors (RECIST), or death due to any cause. Per RECIST, for target lesions (TLs), disease progression (PD) is defined as >=20% increase in the sum of the longest diameters (LD) of TLs, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesions. For non-target lesions (NTLs), PD is defined as the appearance of >=1 new lesions and/or unequivocal progression of existing NTLs. Participants (par.) who did not progress/die were censored at the date of last adequate assessment (LAA). Par. who started a new anti-cancer therapy (ACT) prior to radiological progression/death were censored at the date of LAA prior to the new ACT. Par. who progressed/died after an extended period (>=12 months) without adequate assessment (AA) were censored at the date of their last visit with AA prior to progression/death.
Time Frame	From the date of randomization until the date of progression or death due to any cause (median time of follow-up was 17.9 months for pazopanib and 12.3 months for placebo)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	468	472
Median (95% Confidence Interval); Unit of Measure: months
	12.3; (11.8 to 17.7)	17.9; (15.9 to 21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib 800 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0021
	Comments	The P-value from the stratified log-rank test was adjusted for the two stratification factors.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.766
	Confidence Interval	(2-Sided) 95%; 0.643 to 0.911
	Estimation Comments	The Hazard Ratio was estimated using a Pike estimator.

2. Secondary Outcome

Title	Overall Survival - Median
Description	Overall surival is defined as the interval between the date of randomization and the date of death due to any cause. For participants who did not die, the time to death was censored at the time of last contact.
Time Frame	From the date of randomization until the date of death due to any cause up to approximately 25 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	468	472
Median (95% Confidence Interval); Unit of Measure: months
	64.0; (56.0 to 75.7)	59.1; (53.5 to 71.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib 800 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6431
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified Log-Rank P-Value.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.960
	Confidence Interval	(2-Sided) 95%; 0.805 to 1.145
	Estimation Comments	The HR was estimated using a Pike estimator. CIs were estimated using the Brookmeyer-Crowley method.

3. Secondary Outcome

Title	Overall Survival: Number of Participants Experiencing Death
Description	Overall surival is defined as the interval between the date of randomization and the date of death due to any cause. For participants who did not die, the time to death was censored at the time of last contact.
Time Frame	From the date of randomization until the date of death due to any cause up to approximately 25 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	468	472
Measure Type: Number; Unit of Measure: participants
deaths	253	241
censored, follow up ended (no deaths)	215	231

4. Secondary Outcome

Title	Progression-free Survival Per Gynecologic Cancer Intergroup (GCIG) Criteria
Description	Progression-free survival by GCIG criteria is defined as the time from the date of randomization to the earliest date of disease progression per GCIG criteria or death due to any cause. Progression is defined according to RECIST but can also be based upon serum CA-125. Progression or recurrence based on serum CA-125 levels are defined on the basis of a progressive serial elevation of serum CA-125, according to the following criteria: (1) participants (par.) with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 >=2x the upper normal limit (UNL) on two occasions at least one week apart or; (2) par. with elevated CA-125 pretreatment, which never normalizes, must show evidence of CA-125 >=2x the nadir value on two occasions at least one week apart or; (3) par. with CA-125 in the normal range pretreatment must show evidence of CA-125 >=2x the UNL on two occasions at least one week apart.
Time Frame	From the date of randomization until the date of progression per GCIG criteria or death due to any cause (median time of follow-up was 16.8 months for pazopanib and 11.9 months for placebo)

Outcome Measure Data

Analysis Population Description

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

For participants who did not progress or die, progression-free survival was censored at the time of the last adequate disease assessment.

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	468	472
Median (95% Confidence Interval); Unit of Measure: months
	11.9; (10.6 to 14.9)	16.8; (12.6 to 18.1)

5. Secondary Outcome

Title	3-year Progression-free Survival
Description	3-year progression-free survival is defined as the percentage of participants who are progression-free at 3 years from randomization. Progression-free survival is defined as the time from the date of randomization to the earliest date of disease progression (defined by RECIST) or death due to any cause. Per RECIST, for target lesions, disease progression (PD) is defined as at least a 20% increase in the sum of the longest diameters (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. For non-target lesions, PD is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	Up to 3 years after randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	468	472
Measure Type: Number; Unit of Measure: percentage of participants
	NA [1]	NA [1]

[1]

At the time of data cut-off, only one participant had more than 3 years of follow-up; therefore, 3-year progression-free survival could not be estimated.

6. Secondary Outcome

Title	Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status Score on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25
Description	The EORTC QLQ-C30 is a self-reported, 30-item cancer-specific instrument that assesses 15 domains: 5 functional scales (physical, role, emotional, cognitive, and social functioning), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health status, or quality of life. Global health status is assessed using a 7-item Likert scale, ranging from 1 to 7 ("poor" to "excellent"). Participants were asked to respond to the following questions using the 7-item Likert scale: "How would you rate your overall health during the past week"; "How would you rate your overall quality of life during the past week?" Data are transformed to a scale ranging from 0 to 100. Higher scores represent better functioning (better quality of life). Mean changes from Baseline were calculated via mixed model-repeated measures analysis of covariance (ANCOVA).
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		393	293
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	393 participants	293 participants
		0.58 (0.821)	-3.82 (0.950)
Month 7	Number Analyzed	316 participants	223 participants
		0.95 (0.962)	-4.65 (1.139)
Month 10	Number Analyzed	240 participants	184 participants
		1.98 (0.972)	-4.28 (1.115)
Month 13	Number Analyzed	190 participants	140 participants
		0.65 (1.200)	-1.80 (1.398)
Month 16	Number Analyzed	137 participants	87 participants
		1.39 (1.370)	0.96 (1.702)
Month 25	Number Analyzed	92 participants	53 participants
		3.86 (1.488)	-1.68 (1.934)

7. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Attitude to Disease/Treatment Functional Score on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV (ovarian)-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses attitude to disease/treatment functional symptoms, among others. Participants were asked to indicate the extent to which they experienced attention to disease/treatment functional problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: How much has your disease been a burden to you?; How much has your treatment been a burden to you?; Were you worried about your future health? Data are transformed to a scale ranging from 0 to 100. Higher scores represent better functioning (better quality of life). Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		378	291
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	378 participants	291 participants
		9.92 (1.110)	4.24 (1.263)
Month 7	Number Analyzed	299 participants	223 participants
		12.10 (1.203)	4.94 (1.385)
Month 10	Number Analyzed	228 participants	185 participants
		14.31 (1.310)	8.54 (1.467)
Month 13	Number Analyzed	182 participants	138 participants
		15.45 (1.388)	10.07 (1.589)
Month 16	Number Analyzed	133 participants	88 participants
		15.81 (1.668)	13.25 (2.013)
Month 25	Number Analyzed	90 participants	54 participants
		16.50 (2.021)	5.72 (2.565)

8. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Body Image Functional Score on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses body image symptoms, among others. Participants were asked to indicate the extent to which they experienced body image problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: Have you felt physically less attractive as a result of your disease or treatment?; Have you been dissatisfied with your body? Data are transformed to a scale ranging from 0 to 100. Higher scores represent better functioning (better quality of life). Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		386	297
Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	386 participants	297 participants
		7.18 (1.063)	2.99 (1.210)
Month 7	Number Analyzed	312 participants	230 participants
		7.88 (1.141)	4.26 (1.319)
Month 10	Number Analyzed	236 participants	190 participants
		8.12 (1.319)	4.65 (1.482)
Month 13	Number Analyzed	187 participants	145 participants
		8.54 (1.421)	4.34 (1.616)
Month 16	Number Analyzed	133 participants	91 participants
		7.68 (1.633)	6.21 (1.941)
Month 25	Number Analyzed	88 participants	56 participants
		10.81 (1.856)	3.10 (2.281)

9. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Peripheral Neuropathy (PN) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses peripheral neuropathy symptoms, among others. Participants were asked to indicate the extent to which they experienced peripheral neuropathy symptoms or problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: Did you have tingling hands or feet?; Have you had numbness in your fingers or toes?; Have you felt weak in your arms or legs? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms) for symptom scales. Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		388	297
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	388 participants	297 participants
		-3.34 (1.038)	-5.22 (1.184)
Month 7	Number Analyzed	301 participants	226 participants
		-6.12 (1.104)	-5.20 (1.270)
Month 10	Number Analyzed	235 participants	188 participants
		-7.85 (1.209)	-5.11 (1.361)
Month 13	Number Analyzed	188 participants	140 participants
		-8.76 (1.301)	-6.37 (1.499)
Month 16	Number Analyzed	133 participants	90 participants
		-8.66 (1.456)	-8.65 (1.745)
Month 25	Number Analyzed	91 participants	55 participants
		-9.47 (1.595)	-8.30 (2.010)

10. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Abdominal (AB)/Gastrointestinal (GI) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses AB/GI symptoms, among others. Participants were asked to indicate the extent to which they experienced AB/GI symptoms or problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: Did you have abdominal pain?; Did you have a bloated feeling in your abdomen/stomach?; Did you have problems with your clothes feeling too tight?; Did you experience any change in bowel habit as a result of your disease or treatment?; Were you troubled by passing wind/gas/flatulence?; Have you felt full too quickly after beginning to eat?; Have you had indigestion/heartburn? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms) for symptom scales. Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		388	289
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	388 participants	289 participants
		0.93 (0.673)	6.62 (0.777)
Month 7	Number Analyzed	308 participants	225 participants
		2.36 (0.831)	11.11 (0.967)
Month 10	Number Analyzed	232 participants	187 participants
		2.74 (0.957)	11.33 (0.957)
Month 13	Number Analyzed	187 participants	141 participants
		3.64 (1.027)	12.29 (1.181)
Month 16	Number Analyzed	133 participants	88 participants
		3.69 (1.251)	8.11 (1.503)
Month 25	Number Analyzed	91 participants	54 participants
		3.82 (1.388)	11.86 (1.762)

11. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Hormonal/Menopausal Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses hormonal/menopausal symptoms, among others. Participants were asked to indicate the extent to which they experienced hormonal/menopausal symptoms or problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: Did you have hot flashes?; Did you have night sweats? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms) for symptom scales. Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		398	299
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	398 participants	299 participants
		-0.86 (1.026)	-0.95 (1.177)
Month 7	Number Analyzed	315 participants	232 participants
		-0.38 (1.185)	1.29 (1.371)
Month 10	Number Analyzed	239 participants	189 participants
		-2.17 (1.299)	0.83 (1.470)
Month 13	Number Analyzed	186 participants	144 participants
		-2.77 (1.396)	-0.74 (1.594)
Month 16	Number Analyzed	136 participants	91 participants
		-0.41 (1.610)	1.09 (1.920)
Month 25	Number Analyzed	92 participants	55 participants
		-1.58 (1.798)	-0.68 (2.280)

12. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Sexuality Functional on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses sexual functioning symptoms, among others. Participants were asked to indicate the extent to which they experienced sexual functioning problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: To what extent were you interested in sex?; To what extent were you sexually active?; If sexually active, to what extent was sex enjoyable for you?; If sexually active, did you have a dry vagina during sexual activity? Higher scores represent better functioning (better quality of life). Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA. Data were not analyzed due to low compliance (<50% at Baseline).
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

Data were not analyzed due to low compliance (<50% at Baseline).

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

13. Secondary Outcome

Title	Change From Baseline in QLQ-OV-28 Module Other Chemotherapy Side Effects (SE) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25
Description	The OV-28 module is a 28-item addition to the EORTC QLQ-C30 that focuses on issues specific to ovarian cancer. It assesses other chemotherapy SE symptoms, among others. Participants were asked to indicate the extent to which they experienced other chemotherapy SE symptoms/problems in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following questions: Have you lost any hair?; If yes, were you upset by the loss of your hair?; Did food/drink taste different from usual?; Did you have aches or pains in your muscles or joints?; Did you have problems with hearing?; Did you urinate frequently?; Have you had skin problems (e.g., itchy, dry)? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms) for symptom scales. Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA. Data were not analyzed due to low compliance (<50% at Baseline).
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA. Data were not analyzed due to low compliance (<50% at Baseline).

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

14. Secondary Outcome

Title	Change From Baseline in the EuroQOL EQ-5D (Five Dimensions) Thermometer Score at Week 13 and Months 7, 10, 13, 16, and 25
Description	The EuroQol (EQ-5D) questionnaire is a 2-page, generic, preference-based quality of life measure comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score The thermometer score is based on a vertical VAS. The VAS is designed like a thermometer scale on which the best health state the participant can imagine is referenced at 100, and the worst health state the participant can imagine is marked by 0. Based on how good or bad the current health state is, the participant is asked to draw a line across the thermometer scale. For example, a line drawn across 46 on the scale of 0 to 100 would be coded 46. A negative adjusted mean change from Baseline represents a worsening of quality of life. Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

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

Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		371	288
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	371 participants	288 participants
		1.35 (0.876)	1.20 (0.993)
Month 7	Number Analyzed	301 participants	220 participants
		3.00 (0.929)	1.69 (1.076)
Month 10	Number Analyzed	225 participants	179 participants
		3.68 (1.048)	0.98 (1.179)
Month 13	Number Analyzed	179 participants	136 participants
		2.92 (1.194)	2.49 (1.369)
Month 16	Number Analyzed	127 participants	87 participants
		3.30 (1.219)	3.51 (1.451)
Month 25	Number Analyzed	86 participants	53 participants
		6.87 (1.534)	1.71 (1.937)

15. Secondary Outcome

Title	Change From Baseline in the EQ-5D (Five Dimensions) Utility Score at Week 13 and Months 7, 10, 13, 16, and 25
Description	The EQ-5D utility score captures health status across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety and/or depression. Participants indicated the level of perceived problems in each of the five dimensions on three levels: 1, no problems; 2, some problems; 3, an extreme problem. Unique health states were defined by combining response levels from each of the five dimensions. For example, state 11111 indicates no problem on any of the five dimensions, whereas state 11223 indicates no problems with mobility or self-care; some problems with performing usual activities, moderate pain/discomfort; and extreme anxiety/depression. Responses are typically converted into health utilities or valuations on a scale ranging from 0 (worst health) to 1 (perfect health). A negative adjusted mean change from Baseline represents a worsening of quality of life. Mean changes from Baseline were calculated via mixed model-repeated measures ANCOVA.
Time Frame	Baseline; Week 13; Months 7, 10, 13, 16, and 25

Outcome Measure Data

Analysis Population Description

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

Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		376	293
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
Week 13	Number Analyzed	376 participants	293 participants
		0.00 (0.009)	-0.04 (0.010)
Month 7	Number Analyzed	303 participants	226 participants
		0.00 (0.010)	-0.04 (0.012)
Month 10	Number Analyzed	228 participants	181 participants
		0.01 (0.011)	-0.04 (0.012)
Month 13	Number Analyzed	185 participants	138 participants
		0.01 (0.011)	-0.01 (0.013)
Month 16	Number Analyzed	129 participants	87 participants
		-0.00 (0.014)	0.03 (0.017)
Month 25	Number Analyzed	88 participants	56 participants
		0.00 (0.016)	-0.02 (0.020)

16. Secondary Outcome

Title	Number of Participants With the Indicated Grade 2, 3, and 4 On-therapy Adverse Events Occurring in >=10% of Participants in Either Treatment Arm
Description	An AE is 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. AEs were graded according to the Common Terminiology Criteria for Adverse Events (CTCAE), Version 4.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death.
Time Frame	From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo)

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	461	477
Measure Type: Number; Unit of Measure: participants
Hypertension, G2	52	95
Hypertension, G3	25	139
Hypertension, G4	0	0
Diarrhoea, G2	22	97
Diarrhoea, G3	5	38
Diarrhoea, G4	0	1
Nausea, G2	15	42
Nausea, G3	0	4
Nausea, G4	0	0
Headache, G2	6	36
Headache, G3	3	8
Headache, G4	0	0
Fatigue, G2	19	42
Fatigue, G3	1	7
Fatigue, G4	0	0
Neutropenia, G2	17	51
Neutropenia, G3	2	29
Neutropenia, G4	2	3
Dysgeusia, G2	0	16
Dysgeusia, G3	0	0
Dysgeusia, G4	0	0
Abdominal pain, G2	21	26
Abdominal pain, G3	5	5
Abdominal pain, G4	0	0
Alanine aminotransferase increased, G2	4	22
Alanine aminotransferase increased, G3	0	24
Alanine aminotransferase increased, G4	1	4
Hair color changes, G2	0	13
Hair color changes, G3	0	0
Hair color changes, G4	0	0
Decreased appetite, G2	2	19
Decreased appetite, G3	0	1
Decreased appetite, G4	0	0
Vomiting, G2	8	21
Vomiting, G3	1	4
Vomiting, G4	0	0
Aspartate aminotransferase increased, G2	3	22
Aspartate aminotransferase increased, G3	0	10
Aspartate aminotransferase increased, G4	1	3
Arthralgia, G2	13	19
Arthralgia, G3	3	5
Arthralgia, G4	0	0
Abdominal pain upper, G2	3	20
Abdominal pain upper, G3	1	1
Abdominal pain upper, G4	0	1
Asthenia, G2	8	28
Asthenia, G3	0	6
Asthenia, G4	0	0
Palmar-plantar erythrodysaesthesia syndrome, G2	2	42
Palmar-plantar erythrodysaesthesia syndrome, G3	1	9
Palmar-plantar erythrodysaesthesia syndrome, G4	0	0
Thrombocytopenia, G2	1	15
Thrombocytopenia, G3	1	6
Thrombocytopenia, G4	2	3
Hypothyroidism, G2	9	19
Hypothyroidism, G3	0	0
Hypothyroidism, G4	0	0
Constipation, G2	20	12
Constipation, G3	1	1
Constipation, G4	0	0

17. Secondary Outcome

Title	Number of Participants With the Indicated On-therapy Hematology Grade Shifts From Baseline Grade
Description	Hematology toxicities were graded according to the Common Terminiology Criteria for Adverse Events (CTCAE), Version 4.0. Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death. Participants with a missing Baseline grade were assumed to have a Baseline grade of 0. WBC=White blood cell.
Time Frame	From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo)

Outcome Measure Data

Analysis Population Description

All Treated Population. Only those participants contributing toxicity data were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		456	466
Measure Type: Number; Unit of Measure: participants
Hemoglobin, Any grade increase	Number Analyzed	456 participants	466 participants
		44	68
Hemoglobin, Increase to Grade 3	Number Analyzed	456 participants	466 participants
		0	0
Hemoglobin, Increase to Grade 4	Number Analyzed	456 participants	466 participants
		0	0
Lymphocytes, Any grade increase	Number Analyzed	453 participants	461 participants
		75	91
Lymphocytes, Increase to Grade 3	Number Analyzed	453 participants	461 participants
		1	13
Lymphocytes, Increase to Grade 4	Number Analyzed	453 participants	461 participants
		0	0
Neutrophils, Any grade increase	Number Analyzed	455 participants	462 participants
		80	236
Neutrophils, Increase to Grade 3	Number Analyzed	455 participants	462 participants
		2	44
Neutrophils, Increase to Grade 4	Number Analyzed	455 participants	462 participants
		0	5
Platelets, Any grade increase	Number Analyzed	456 participants	465 participants
		25	167
Platelets, Increase to Grade 3	Number Analyzed	456 participants	465 participants
		1	8
Platelets, Increase to Grade 4	Number Analyzed	456 participants	465 participants
		1	4
WBC count, Any grade increase	Number Analyzed	456 participants	465 participants
		77	236
WBC count, Increase to Grade 3	Number Analyzed	456 participants	465 participants
		0	11
WBC count, Increase to Grade 4	Number Analyzed	456 participants	465 participants
		0	1

18. Secondary Outcome

Title	Number of Participants With the Indicated On-therapy Chemistry Grade Shifts From Baseline Grade
Description	Hematology toxicities were graded according to the Common Terminiology Criteria for Adverse Events (CTCAE), Version 4.0. Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death. Participants with a missing Baseline grade were assumed to have a Baseline grade of 0.
Time Frame	From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo)

Outcome Measure Data

Analysis Population Description

All Treated Population. Only those participants contributing toxicity data were analyzed.

Arm/Group Title		Placebo	Pazopanib 800 mg
Arm/Group Description:		Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed		456	465
Measure Type: Number; Unit of Measure: participants
Albumin, Any grade increase	Number Analyzed	450 participants	455 participants
		33	50
Albumin, Increase to Grade 3	Number Analyzed	450 participants	455 participants
		0	0
Albumin, Increase to Grade 4	Number Analyzed	450 participants	455 participants
		0	0
Creatinine, Any grade increase	Number Analyzed	456 participants	465 participants
		27	42
Creatinine, Increase to Grade 3	Number Analyzed	456 participants	465 participants
		0	1
Creatinine, Increase to Grade 4	Number Analyzed	456 participants	465 participants
		0	0
Hypercalcemia, Any grade increase	Number Analyzed	456 participants	462 participants
		33	16
Hypercalcemia, Increase to Grade 3	Number Analyzed	456 participants	462 participants
		0	0
Hypercalcemia, Increase to Grade 4	Number Analyzed	456 participants	462 participants
		0	0
Hyperglycemia, Any grade increase	Number Analyzed	446 participants	453 participants
		117	128
Hyperglycemia, Increase to Grade 3	Number Analyzed	446 participants	453 participants
		10	2
Hyperglycemia, Increase to Grade 4	Number Analyzed	446 participants	453 participants
		0	0
Hyperkalemia, Any grade increase	Number Analyzed	455 participants	464 participants
		39	38
Hyperkalemia, Increase to Grade 3	Number Analyzed	455 participants	464 participants
		2	1
Hyperkalemia, Increase to Grade 4	Number Analyzed	455 participants	464 participants
		0	2
Hypermagnesemia, Any grade increase	Number Analyzed	439 participants	447 participants
		11	20
Hypermagnesemia, Increase to Grade 3	Number Analyzed	439 participants	447 participants
		1	6
Hypermagnesemia, Increase to Grade 4	Number Analyzed	439 participants	447 participants
		1	0
Hypernatremia, Any grade increase	Number Analyzed	455 participants	463 participants
		26	25
Hypernatremia, Increase to Grade 3	Number Analyzed	455 participants	463 participants
		0	0
Hypernatremia, Increase to Grade 4	Number Analyzed	455 participants	463 participants
		0	0
Hypocalcemia, Any grade increase	Number Analyzed	456 participants	462 participants
		21	52
Hypocalcemia, Increase to Grade 3	Number Analyzed	456 participants	462 participants
		0	2
Hypocalcemia, Increase to Grade 4	Number Analyzed	456 participants	462 participants
		0	0
Hypoglycemia, Any grade increase	Number Analyzed	446 participants	453 participants
		25	41
Hypoglycemia, Increase to Grade 3	Number Analyzed	446 participants	453 participants
		2	0
Hypoglycemia, Increase to Grade 4	Number Analyzed	446 participants	453 participants
		2	2
Hypokalemia, Any grade increase	Number Analyzed	455 participants	464 participants
		31	40
Hypokalemia, Increase to Grade 3	Number Analyzed	455 participants	464 participants
		1	2
Hypokalemia, Increase to Grade 4	Number Analyzed	455 participants	464 participants
		1	0
Hypomagnesemia, Any grade increase	Number Analyzed	439 participants	447 participants
		55	65
Hypomagnesemia, Increase to Grade 3	Number Analyzed	439 participants	447 participants
		3	1
Hypomagnesemia, Increase to Grade 4	Number Analyzed	439 participants	447 participants
		0	2
Hyponatremia, Any grade increase	Number Analyzed	455 participants	463 participants
		37	45
Hyponatremia, Increase to Grade 3	Number Analyzed	455 participants	463 participants
		5	9
Hyponatremia, Increase to Grade 4	Number Analyzed	455 participants	463 participants
		0	0
Phosphate, Any grade increase	Number Analyzed	409 participants	401 participants
		33	24
Phosphate, Increase to Grade 3	Number Analyzed	409 participants	401 participants
		4	0
Phosphate, Increase to Grade 4	Number Analyzed	409 participants	401 participants
		0	1

19. Secondary Outcome

Title	Number of Participants With the Indicated Treatment-emergent Thyroid-stimulating Hormone (TSH) Elevations Above 5 Million Units Per Liter (MU/L)
Description	Participants were assessed for thyroid function abnormalities. Clinical hypothyroidism is defined as 5 <TSH <=10 MU/L and T4 <lower limit of normal (LLN).
Time Frame	From the date of the first dose of study drug to the date of the last dose plus 28 days (average of 9.8 months for pazopanib and 12.6 months for placebo)

Outcome Measure Data

Analysis Population Description

All Treated Population. Only those participants with any TSH above 5 MU/L were analyzed.

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	42	157
Measure Type: Number; Unit of Measure: participants
5 <TSH <=10 MU/L	34	94
10 <TSH <=20 MU/L	4	36
TSH >20 MU/L	4	27

20. Post-Hoc Outcome

Title	All Collected Deaths
Description	On-treatment deaths were collected from first dose of study treatment up to 28 days after study drug discontinuation, for a maximum duration of 27 months. Deaths post treatment survival follow up were collected after the on treatment period, up to 96 months (8 years).
Time Frame	on-treatment: up to 27 months; post-treatment: up to 96 months (8 years).

Outcome Measure Data

Analysis Population Description

Treated set.

One randomized patient in each treatment arm was excluded from the All Treated population because they did not receive treatment. The pazopanib group included 6 patients who were randomized to placebo but took at least one dose of pazopanib.

Four patients (one in placebo, three in pazopanib) had missing death dates and therefore were treated as censored at the last contact date.

Arm/Group Title	Placebo	Pazopanib 800 mg
Arm/Group Description:	Participants received matching placebo once daily for a maximum of 24 months.	Participants received pazopanib 800 milligrams (mg) once daily for a maximum of 24 months.
Overall Number of Participants Analyzed	461	477
Measure Type: Number; Unit of Measure: participants
All Treated Population	461	477
Total deaths	252	245
On-treatment Deaths - occurring less than or equal to 28 days from last dose	0	3

Adverse Events

Time Frame	Adverse events were reported from first dose of study treatment until end of study treatment plus 28 days post treatment, up to a maximum duration of approximately 25 months.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo	Pazopanib
Arm/Group Description	Participants received matching placebo once daily for a maximum of 24 months.	Pazopanib
All-Cause Mortality
	Placebo	Pazopanib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/461 (0.00%)	3/477 (0.63%)
Serious Adverse Events
	Placebo	Pazopanib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	51/461 (11.06%)	121/477 (25.37%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	1/461 (0.22%)	2/477 (0.42%)
Neutropenia † 1	0/461 (0.00%)	2/477 (0.42%)
Thrombocytopenia † 1	1/461 (0.22%)	4/477 (0.84%)
Cardiac disorders
Acute coronary syndrome † 1	1/461 (0.22%)	0/477 (0.00%)
Angina pectoris † 1	0/461 (0.00%)	1/477 (0.21%)
Bradycardia † 1	0/461 (0.00%)	1/477 (0.21%)
Cardiac failure † 1	0/461 (0.00%)	1/477 (0.21%)
Cardiomyopathy † 1	0/461 (0.00%)	1/477 (0.21%)
Coronary artery disease † 1	0/461 (0.00%)	1/477 (0.21%)
Coronary artery insufficiency † 1	1/461 (0.22%)	0/477 (0.00%)
Myocardial infarction † 1	0/461 (0.00%)	2/477 (0.42%)
Myocardial ischaemia † 1	0/461 (0.00%)	1/477 (0.21%)
Sinus bradycardia † 1	0/461 (0.00%)	1/477 (0.21%)
Ventricular tachycardia † 1	0/461 (0.00%)	1/477 (0.21%)
Ear and labyrinth disorders
Vertigo † 1	0/461 (0.00%)	1/477 (0.21%)
Eye disorders
Vitreous detachment † 1	0/461 (0.00%)	1/477 (0.21%)
Vitreous floaters † 1	0/461 (0.00%)	1/477 (0.21%)
Vitreous haemorrhage † 1	0/461 (0.00%)	2/477 (0.42%)
Gastrointestinal disorders
Abdominal mass † 1	1/461 (0.22%)	0/477 (0.00%)
Abdominal pain † 1	3/461 (0.65%)	3/477 (0.63%)
Abdominal pain lower † 1	0/461 (0.00%)	1/477 (0.21%)
Abdominal pain upper † 1	1/461 (0.22%)	0/477 (0.00%)
Anal haemorrhage † 1	1/461 (0.22%)	0/477 (0.00%)
Ascites † 1	1/461 (0.22%)	1/477 (0.21%)
Constipation † 1	1/461 (0.22%)	1/477 (0.21%)
Diarrhoea † 1	2/461 (0.43%)	3/477 (0.63%)
Duodenitis † 1	0/461 (0.00%)	1/477 (0.21%)
Enterocele † 1	0/461 (0.00%)	1/477 (0.21%)
Gastric ulcer perforation † 1	0/461 (0.00%)	2/477 (0.42%)
Gastrointestinal haemorrhage † 1	0/461 (0.00%)	1/477 (0.21%)
Ileus † 1	0/461 (0.00%)	2/477 (0.42%)
Intestinal obstruction † 1	3/461 (0.65%)	3/477 (0.63%)
Large intestinal obstruction † 1	1/461 (0.22%)	0/477 (0.00%)
Nausea † 1	1/461 (0.22%)	2/477 (0.42%)
Pancreatitis acute † 1	0/461 (0.00%)	1/477 (0.21%)
Rectal haemorrhage † 1	0/461 (0.00%)	1/477 (0.21%)
Small intestinal obstruction † 1	1/461 (0.22%)	1/477 (0.21%)
Subileus † 1	3/461 (0.65%)	1/477 (0.21%)
Vomiting † 1	2/461 (0.43%)	4/477 (0.84%)
General disorders
Asthenia † 1	1/461 (0.22%)	0/477 (0.00%)
Fatigue † 1	0/461 (0.00%)	2/477 (0.42%)
Fibrosis † 1	0/461 (0.00%)	1/477 (0.21%)
General physical health deterioration † 1	1/461 (0.22%)	4/477 (0.84%)
Hernia † 1	1/461 (0.22%)	2/477 (0.42%)
Ill-defined disorder † 1	1/461 (0.22%)	0/477 (0.00%)
Influenza like illness † 1	1/461 (0.22%)	0/477 (0.00%)
Pyrexia † 1	2/461 (0.43%)	9/477 (1.89%)
Hepatobiliary disorders
Cholecystitis † 1	0/461 (0.00%)	1/477 (0.21%)
Cholecystitis acute † 1	0/461 (0.00%)	1/477 (0.21%)
Hepatocellular injury † 1	0/461 (0.00%)	1/477 (0.21%)
Hepatotoxicity † 1	0/461 (0.00%)	3/477 (0.63%)
Immune system disorders
Cytokine release syndrome † 1	0/461 (0.00%)	1/477 (0.21%)
Drug hypersensitivity † 1	0/461 (0.00%)	1/477 (0.21%)
Hypersensitivity † 1	0/461 (0.00%)	2/477 (0.42%)
Sarcoidosis † 1	1/461 (0.22%)	0/477 (0.00%)
Infections and infestations
Bronchitis † 1	1/461 (0.22%)	0/477 (0.00%)
Erysipelas † 1	1/461 (0.22%)	0/477 (0.00%)
Gastroenteritis † 1	1/461 (0.22%)	1/477 (0.21%)
Gastroenteritis norovirus † 1	0/461 (0.00%)	1/477 (0.21%)
Infected lymphocele † 1	1/461 (0.22%)	1/477 (0.21%)
Infectious colitis † 1	1/461 (0.22%)	0/477 (0.00%)
Infectious pleural effusion † 1	0/461 (0.00%)	1/477 (0.21%)
Localised infection † 1	1/461 (0.22%)	0/477 (0.00%)
Pelvic abscess † 1	0/461 (0.00%)	1/477 (0.21%)
Pharyngotonsillitis † 1	0/461 (0.00%)	1/477 (0.21%)
Pneumonia † 1	0/461 (0.00%)	2/477 (0.42%)
Pyelonephritis † 1	0/461 (0.00%)	1/477 (0.21%)
Respiratory tract infection † 1	0/461 (0.00%)	1/477 (0.21%)
Subcutaneous abscess † 1	0/461 (0.00%)	1/477 (0.21%)
Tooth abscess † 1	1/461 (0.22%)	0/477 (0.00%)
Urinary tract infection † 1	3/461 (0.65%)	0/477 (0.00%)
Injury, poisoning and procedural complications
Contusion † 1	1/461 (0.22%)	0/477 (0.00%)
Fall † 1	1/461 (0.22%)	0/477 (0.00%)
Incisional hernia † 1	1/461 (0.22%)	0/477 (0.00%)
Overdose † 1	1/461 (0.22%)	0/477 (0.00%)
Procedural complication † 1	0/461 (0.00%)	1/477 (0.21%)
Thermal burn † 1	0/461 (0.00%)	1/477 (0.21%)
Tibia fracture † 1	1/461 (0.22%)	0/477 (0.00%)
Upper limb fracture † 1	1/461 (0.22%)	0/477 (0.00%)
Wound dehiscence † 1	0/461 (0.00%)	1/477 (0.21%)
Investigations
Alanine aminotransferase increased † 1	0/461 (0.00%)	18/477 (3.77%)
Aspartate aminotransferase increased † 1	0/461 (0.00%)	7/477 (1.47%)
Blood bilirubin increased † 1	0/461 (0.00%)	2/477 (0.42%)
Blood lactate dehydrogenase increased † 1	0/461 (0.00%)	1/477 (0.21%)
Ejection fraction decreased † 1	0/461 (0.00%)	1/477 (0.21%)
Electrocardiogram QT prolonged † 1	1/461 (0.22%)	0/477 (0.00%)
Electrocardiogram abnormal † 1	0/461 (0.00%)	1/477 (0.21%)
Gamma-glutamyltransferase increased † 1	0/461 (0.00%)	2/477 (0.42%)
Hepatic enzyme increased † 1	0/461 (0.00%)	5/477 (1.05%)
Liver function test abnormal † 1	0/461 (0.00%)	1/477 (0.21%)
Neutrophil count decreased † 1	0/461 (0.00%)	1/477 (0.21%)
Platelet count decreased † 1	0/461 (0.00%)	1/477 (0.21%)
Transaminases increased † 1	0/461 (0.00%)	3/477 (0.63%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/461 (0.00%)	1/477 (0.21%)
Dehydration † 1	0/461 (0.00%)	1/477 (0.21%)
Hypoglycaemia † 1	0/461 (0.00%)	1/477 (0.21%)
Hypokalaemia † 1	1/461 (0.22%)	0/477 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	0/461 (0.00%)	1/477 (0.21%)
Intervertebral disc protrusion † 1	0/461 (0.00%)	1/477 (0.21%)
Musculoskeletal chest pain † 1	0/461 (0.00%)	1/477 (0.21%)
Myalgia intercostal † 1	0/461 (0.00%)	1/477 (0.21%)
Rheumatoid arthritis † 1	1/461 (0.22%)	0/477 (0.00%)
Rotator cuff syndrome † 1	1/461 (0.22%)	0/477 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign † 1	1/461 (0.22%)	0/477 (0.00%)
Intraductal proliferative breast lesion † 1	1/461 (0.22%)	0/477 (0.00%)
Malignant lymphoma unclassifiable low grade † 1	1/461 (0.22%)	0/477 (0.00%)
Malignant neoplasm of unknown primary site † 1	0/461 (0.00%)	1/477 (0.21%)
Metastases to abdominal cavity † 1	0/461 (0.00%)	1/477 (0.21%)
Squamous cell carcinoma of skin † 1	1/461 (0.22%)	0/477 (0.00%)
Thyroid adenoma † 1	0/461 (0.00%)	1/477 (0.21%)
Ulcerated haemangioma † 1	0/461 (0.00%)	1/477 (0.21%)
Nervous system disorders
Cranial nerve disorder † 1	1/461 (0.22%)	0/477 (0.00%)
Headache † 1	0/461 (0.00%)	2/477 (0.42%)
Intercostal neuralgia † 1	0/461 (0.00%)	1/477 (0.21%)
Ischaemic stroke † 1	0/461 (0.00%)	1/477 (0.21%)
Migraine † 1	0/461 (0.00%)	2/477 (0.42%)
Paraesthesia † 1	0/461 (0.00%)	1/477 (0.21%)
Posterior reversible encephalopathy syndrome † 1	0/461 (0.00%)	1/477 (0.21%)
Presyncope † 1	0/461 (0.00%)	1/477 (0.21%)
Seizure † 1	0/461 (0.00%)	1/477 (0.21%)
Transverse sinus thrombosis † 1	0/461 (0.00%)	1/477 (0.21%)
Product Issues
Device breakage † 1	1/461 (0.22%)	0/477 (0.00%)
Renal and urinary disorders
Haematuria † 1	0/461 (0.00%)	1/477 (0.21%)
Hydronephrosis † 1	2/461 (0.43%)	0/477 (0.00%)
Urinary retention † 1	1/461 (0.22%)	0/477 (0.00%)
Urinary tract obstruction † 1	0/461 (0.00%)	1/477 (0.21%)
Reproductive system and breast disorders
Female genital tract fistula † 1	0/461 (0.00%)	1/477 (0.21%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis † 1	0/461 (0.00%)	1/477 (0.21%)
Pleural effusion † 1	1/461 (0.22%)	1/477 (0.21%)
Pulmonary embolism † 1	0/461 (0.00%)	2/477 (0.42%)
Skin and subcutaneous tissue disorders
Drug eruption † 1	0/461 (0.00%)	1/477 (0.21%)
Erythema multiforme † 1	0/461 (0.00%)	1/477 (0.21%)
Palmar-plantar erythrodysaesthesia syndrome † 1	0/461 (0.00%)	2/477 (0.42%)
Rash † 1	0/461 (0.00%)	1/477 (0.21%)
Vascular disorders
Arterial thrombosis † 1	0/461 (0.00%)	1/477 (0.21%)
Hypertension † 1	0/461 (0.00%)	8/477 (1.68%)
Hypertensive crisis † 1	0/461 (0.00%)	4/477 (0.84%)
Lymphocele † 1	1/461 (0.22%)	0/477 (0.00%)
1 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Pazopanib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	381/461 (82.65%)	462/477 (96.86%)
Blood and lymphatic system disorders
Leukopenia † 1	5/461 (1.08%)	44/477 (9.22%)
Neutropenia † 1	23/461 (4.99%)	103/477 (21.59%)
Thrombocytopenia † 1	8/461 (1.74%)	48/477 (10.06%)
Endocrine disorders
Hypothyroidism † 1	15/461 (3.25%)	49/477 (10.27%)
Gastrointestinal disorders
Abdominal pain † 1	94/461 (20.39%)	88/477 (18.45%)
Abdominal pain upper † 1	30/461 (6.51%)	67/477 (14.05%)
Constipation † 1	72/461 (15.62%)	38/477 (7.97%)
Diarrhoea † 1	79/461 (17.14%)	252/477 (52.83%)
Dyspepsia † 1	17/461 (3.69%)	24/477 (5.03%)
Nausea † 1	81/461 (17.57%)	174/477 (36.48%)
Stomatitis † 1	7/461 (1.52%)	27/477 (5.66%)
Vomiting † 1	39/461 (8.46%)	71/477 (14.88%)
General disorders
Asthenia † 1	55/461 (11.93%)	66/477 (13.84%)
Fatigue † 1	66/461 (14.32%)	133/477 (27.88%)
Mucosal inflammation † 1	10/461 (2.17%)	32/477 (6.71%)
Infections and infestations
Urinary tract infection † 1	33/461 (7.16%)	32/477 (6.71%)
Viral upper respiratory tract infection † 1	24/461 (5.21%)	27/477 (5.66%)
Investigations
Alanine aminotransferase increased † 1	25/461 (5.42%)	73/477 (15.30%)
Aspartate aminotransferase increased † 1	24/461 (5.21%)	66/477 (13.84%)
Blood alkaline phosphatase increased † 1	3/461 (0.65%)	24/477 (5.03%)
Blood bilirubin increased † 1	1/461 (0.22%)	29/477 (6.08%)
Blood thyroid stimulating hormone increased † 1	1/461 (0.22%)	32/477 (6.71%)
Neutrophil count decreased † 1	11/461 (2.39%)	36/477 (7.55%)
Platelet count decreased † 1	1/461 (0.22%)	30/477 (6.29%)
Metabolism and nutrition disorders
Decreased appetite † 1	15/461 (3.25%)	79/477 (16.56%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	68/461 (14.75%)	71/477 (14.88%)
Back pain † 1	38/461 (8.24%)	30/477 (6.29%)
Muscle spasms † 1	20/461 (4.34%)	35/477 (7.34%)
Myalgia † 1	34/461 (7.38%)	45/477 (9.43%)
Pain in extremity † 1	18/461 (3.90%)	38/477 (7.97%)
Nervous system disorders
Dizziness † 1	22/461 (4.77%)	26/477 (5.45%)
Dysgeusia † 1	13/461 (2.82%)	95/477 (19.92%)
Headache † 1	70/461 (15.18%)	135/477 (28.30%)
Psychiatric disorders
Insomnia † 1	27/461 (5.86%)	24/477 (5.03%)
Renal and urinary disorders
Proteinuria † 1	8/461 (1.74%)	40/477 (8.39%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	20/461 (4.34%)	24/477 (5.03%)
Dyspnoea † 1	21/461 (4.56%)	31/477 (6.50%)
Skin and subcutaneous tissue disorders
Hair colour changes † 1	8/461 (1.74%)	95/477 (19.92%)
Palmar-plantar erythrodysaesthesia syndrome † 1	7/461 (1.52%)	61/477 (12.79%)
Rash † 1	22/461 (4.77%)	42/477 (8.81%)
Vascular disorders
Hot flush † 1	29/461 (6.29%)	23/477 (4.82%)
Hypertension † 1	87/461 (18.87%)	256/477 (53.67%)
1 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety

Results Point of Contact

• Name/Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: Novartis.email@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P. Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2019 Nov;155(2):186-191. doi: 10.1016/j.ygyno.2019.08.024. Epub 2019 Sep 10.

Friedlander M, Rau J, Lee CK, Meier W, Lesoin A, Kim JW, Poveda A, Buck M, Scambia G, Shimada M, Hilpert F, King MT, Debruyne P, Bologna A, Malander S, Monk BJ, Petru E, Calvert P, Herzog TJ, Barrett C, du Bois A. Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters-patient-centered end points in trials of maintenance therapy. Ann Oncol. 2018 Mar 1;29(3):737-743. doi: 10.1093/annonc/mdx796.

Pulford DJ, Harter P, Floquet A, Barrett C, Suh DH, Friedlander M, Arranz JA, Hasegawa K, Tada H, Vuylsteke P, Mirza MR, Donadello N, Scambia G, Johnson T, Cox C, Chan JK, Imhof M, Herzog TJ, Calvert P, Wimberger P, Berton-Rigaud D, Lim MC, Elser G, Xu CF, du Bois A. Communicating BRCA research results to patients enrolled in international clinical trials: lessons learnt from the AGO-OVAR 16 study. BMC Med Ethics. 2016 Oct 21;17(1):63. doi: 10.1186/s12910-016-0144-y.

Kim JW, Mahner S, Wu LY, Shoji T, Kim BG, Zhu JQ, Takano T, Park SY, Kong BH, Wu Q, Wang KL, Ngan HY, Liu JH, Wei LH, Mitrica I, Zhang P, Crescenzo R, Wang Q, Cox CJ, Harter P, du Bois A. Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer. 2018 Jan;28(1):2-10. doi: 10.1097/IGC.0000000000000602.

Floquet A, Vergote I, Colombo N, Fiane B, Monk BJ, Reinthaller A, Calvert P, Herzog TJ, Meier W, Kim JW, del Campo JM, Friedlander M, Pisano C, Isonishi S, Crescenzo RJ, Barrett C, Wang K, Mitrica I, du Bois A. Progression-free survival by local investigator versus independent central review: comparative analysis of the AGO-OVAR16 Trial. Gynecol Oncol. 2015 Jan;136(1):37-42. doi: 10.1016/j.ygyno.2014.11.074. Epub 2014 Nov 28.

du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol. 2014 Oct 20;32(30):3374-82. doi: 10.1200/JCO.2014.55.7348. Epub 2014 Sep 15.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT00866697
• Other Study ID Numbers: 110655; 2008-004672-50 ( EudraCT Number ); CPZP034C2301 ( Other Identifier: Novartis )
• First Submitted: March 19, 2009
• First Posted: March 20, 2009
• Results First Submitted: July 3, 2013
• Results First Posted: December 19, 2013
• Last Update Posted: February 16, 2021