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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00866697
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 940
• Locations: 318
• Arms: 2
• Actual Duration (Months): 99
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Pazopanib; Drug: Placebo	Phase 3

Detailed Description

This was a randomized, two-arm, placebo controlled, double-blind, multicenter, intergroup Phase III study in women with non-bulky FIGO (International Federation of Gynecology and Obstetrics) Stage II - IV ovarian, fallopian tube, or primary peritoneal cancer that had not progressed (i.e., complete response (CR), partial response (PR), stable disease (SD) after completing their first-line chemotherapy for advanced ovarian cancer. Approximately 900 subjects were to be enrolled into the study. Study was closed following 3rd overall survival (OS) interim analysis as planned per protocol, which confirmed futility.

Study Design

• Study Type: Interventional
• Actual Enrollment: 940 participants
• Allocation: Randomized
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III Study to Evaluate the Efficacy and Safety of Pazopanib Monotherapy Versus Placebo in Women Who Have Not Progressed After First Line Chemotherapy for Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
• Actual Study Start Date: May 26, 2009
• Actual Primary Completion Date: Jul 8, 2012
• Actual Study Completion Date: Aug 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo matched placebo tablet administered orally once daily for up to 24 months	Drug: Placebo; Matching placebo 800 mg tablet daily, for 104 weeks (24 months).
Experimental: Pazopanib Pazopanib tablet administered orally at 800 mg once daily for up to 24 months	Drug: Pazopanib; Pazopanib 800 mg tablet daily for 104 weeks (24 months)

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

1. Overall Survival - Median [From the date of randomization until the date of death due to any cause up to approximately 25 months]

   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.

2. Overall Survival: Number of Participants Experiencing Death [From the date of randomization until the date of death due to any cause up to approximately 25 months]

   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.

3. Progression-free Survival Per Gynecologic Cancer Intergroup (GCIG) Criteria [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)]

   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.

4. 3-year Progression-free Survival [Up to 3 years after randomization]

   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.

5. 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 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

   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).

6. 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 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

   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.

7. 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 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

   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.

8. Change From Baseline in QLQ-OV-28 Module Peripheral Neuropathy (PN) Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

   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.

9. 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 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

   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.

10. Change From Baseline in QLQ-OV-28 Module Hormonal/Menopausal Symptoms Score at Week 13 and Months 7, 10, 13, 16, and 25 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

    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.

11. Change From Baseline in QLQ-OV-28 Module Sexuality Functional on Day 1 of Week 13 and Months 7, 10, 13, 16, and 25 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

    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).

12. 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 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

    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).

13. Change From Baseline in the EuroQOL EQ-5D (Five Dimensions) Thermometer Score at Week 13 and Months 7, 10, 13, 16, and 25 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

    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.

14. Change From Baseline in the EQ-5D (Five Dimensions) Utility Score at Week 13 and Months 7, 10, 13, 16, and 25 [Baseline; Week 13; Months 7, 10, 13, 16, and 25]

    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.

15. Number of Participants With the Indicated Grade 2, 3, and 4 On-therapy Adverse Events Occurring in >=10% of Participants in Either Treatment Arm [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)]

    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.

16. Number of Participants With the Indicated On-therapy Hematology Grade Shifts From Baseline Grade [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)]

    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.

17. Number of Participants With the Indicated On-therapy Chemistry Grade Shifts From Baseline Grade [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)]

    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.

18. Number of Participants With the Indicated Treatment-emergent Thyroid-stimulating Hormone (TSH) Elevations Above 5 Million Units Per Liter (MU/L) [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)]

    Participants were assessed for thyroid function abnormalities. Clinical hypothyroidism is defined as 5 <TSH <=10 MU/L and T4 <lower limit of normal (LLN).

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, 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

• ECOG status of 0 or 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

• Cardiac angioplasty or stenting

• Myocardial infarction

• Unstable angina

• Symptomatic peripheral vascular disease

• Class III or IV congestive heart failure

• 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

• Invasive malignancies that showed activity of disease within 5 years prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anaheim	California	United States	92807
2	Novartis Investigative Site	Baldwin Park	California	United States	91706
3	Novartis Investigative Site	Bellflower	California	United States	90706
4	Novartis Investigative Site	Duarte	California	United States	91010
5	Novartis Investigative Site	Fontana	California	United States	92335
6	Novartis Investigative Site	Hayward	California	United States	94545
7	Novartis Investigative Site	Irvine	California	United States	92618
8	Novartis Investigative Site	Long Beach	California	United States	90806
9	Novartis Investigative Site	Los Angeles	California	United States	90027
10	Novartis Investigative Site	Los Angeles	California	United States	90034
11	Novartis Investigative Site	Los Angeles	California	United States	90095
12	Novartis Investigative Site	Oakland	California	United States	94611
13	Novartis Investigative Site	Ontario	California	United States	91761
14	Novartis Investigative Site	Orange	California	United States	92868
15	Novartis Investigative Site	Panorama City	California	United States	91402
16	Novartis Investigative Site	Riverside	California	United States	92505
17	Novartis Investigative Site	Roseville	California	United States	95661
18	Novartis Investigative Site	Sacramento	California	United States	95817
19	Novartis Investigative Site	Sacramento	California	United States	95825
20	Novartis Investigative Site	San Diego	California	United States	92108
21	Novartis Investigative Site	San Diego	California	United States	92120
22	Novartis Investigative Site	San Francisco	California	United States	94115
23	Novartis Investigative Site	San Jose	California	United States	95119-1110
24	Novartis Investigative Site	Santa Clara	California	United States	95051
25	Novartis Investigative Site	South San Francisco	California	United States	94080
26	Novartis Investigative Site	Vallejo	California	United States	94589
27	Novartis Investigative Site	Walnut Creek	California	United States	94596
28	Novartis Investigative Site	Woodland Hills	California	United States	91367
29	Novartis Investigative Site	Augusta	Georgia	United States	30912
30	Novartis Investigative Site	Morristown	New Jersey	United States	07962-1956
31	Novartis Investigative Site	Bronx	New York	United States	10461
32	Novartis Investigative Site	New York	New York	United States	10032
33	Novartis Investigative Site	New York	New York	United States	10065
34	Novartis Investigative Site	Houston	Texas	United States	77030
35	Novartis Investigative Site	Annandale	Virginia	United States	22003
36	Novartis Investigative Site	Camperdown	New South Wales	Australia	2050
37	Novartis Investigative Site	Liverpool	New South Wales	Australia	2170
38	Novartis Investigative Site	Randwick	New South Wales	Australia	2031
39	Novartis Investigative Site	Waratah	New South Wales	Australia	2298
40	Novartis Investigative Site	Herston	Queensland	Australia	4029
41	Novartis Investigative Site	South Brisbane	Queensland	Australia	4101
42	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
43	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
44	Novartis Investigative Site	Malvern	Victoria	Australia	3144
45	Novartis Investigative Site	Parkville	Victoria	Australia	3052
46	Novartis Investigative Site	Wodonga	Victoria	Australia	3690
47	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
48	Novartis Investigative Site	Melbourne		Australia	3084
49	Novartis Investigative Site	Graz		Austria	8020
50	Novartis Investigative Site	Graz		Austria	A-8036
51	Novartis Investigative Site	Innsbruck		Austria	6020
52	Novartis Investigative Site	Klagenfurt Am Woerthersee		Austria	9020
53	Novartis Investigative Site	Korneuburg		Austria	2100
54	Novartis Investigative Site	Krems		Austria	3500
55	Novartis Investigative Site	Leoben		Austria	8700
56	Novartis Investigative Site	Linz		Austria	4010
57	Novartis Investigative Site	Linz		Austria	4020
58	Novartis Investigative Site	Oberpullendorf		Austria	7350
59	Novartis Investigative Site	Wien		Austria	1090
60	Novartis Investigative Site	Wien		Austria	1130
61	Novartis Investigative Site	Wien		Austria	1160
62	Novartis Investigative Site	Bonheiden		Belgium	2820
63	Novartis Investigative Site	Duffel		Belgium	2570
64	Novartis Investigative Site	Gent		Belgium	9000
65	Novartis Investigative Site	Kortrijk		Belgium	8500
66	Novartis Investigative Site	Leuven		Belgium	3000
67	Novartis Investigative Site	Libramont		Belgium	6800
68	Novartis Investigative Site	Liege		Belgium	4000
69	Novartis Investigative Site	Namur		Belgium	5000
70	Novartis Investigative Site	Oostende		Belgium	8400
71	Novartis Investigative Site	Guangzhou	Guangdong	China
72	Novartis Investigative Site	Nanjing	Jiangsu	China	210009
73	Novartis Investigative Site	Shenyang	Liaoning	China	110022
74	Novartis Investigative Site	Jinan	Shandong	China	250012
75	Novartis Investigative Site	Hangzhou	Zhejiang	China	310006
76	Novartis Investigative Site	Hangzhou	Zhejiang	China	310022
77	Novartis Investigative Site	Beijing		China	100021
78	Novartis Investigative Site	Beijing		China	100044
79	Novartis Investigative Site	Beijing		China	100141
80	Novartis Investigative Site	Beijing		China	100853
81	Novartis Investigative Site	Shanghai		China	200011
82	Novartis Investigative Site	Shanghai		China	200032
83	Novartis Investigative Site	Tianjin		China	300060
84	Novartis Investigative Site	Aalborg		Denmark	9100
85	Novartis Investigative Site	Herlev		Denmark	DK-2730
86	Novartis Investigative Site	Herning		Denmark	7400
87	Novartis Investigative Site	Koebenhavn Oe		Denmark	2100
88	Novartis Investigative Site	ANGERS Cedex 2		France	49055
89	Novartis Investigative Site	Avignon cedex		France	84902
90	Novartis Investigative Site	Besancon Cedex		France	25030
91	Novartis Investigative Site	Bordeaux		France	33000
92	Novartis Investigative Site	Bordeaux		France	33076
93	Novartis Investigative Site	Bordeaux		France	33300
94	Novartis Investigative Site	Bourg en Bresse Cedex		France	01012
95	Novartis Investigative Site	Brest Cedex		France	29609
96	Novartis Investigative Site	Brive La Gaillarde		France	19100
97	Novartis Investigative Site	Caen Cedex 05		France	14076
98	Novartis Investigative Site	Clermont-Ferrand cedex		France	63011
99	Novartis Investigative Site	Colmar Cedex		France	68024
100	Novartis Investigative Site	Dax Cedex		France	40107
101	Novartis Investigative Site	Grenoble Cedex 09		France	38043
102	Novartis Investigative Site	Grenoble Cedex		France	38028
103	Novartis Investigative Site	La Roche sur Yon Cedex 9		France	85925
104	Novartis Investigative Site	Le Chesnay Cedex		France	78157
105	Novartis Investigative Site	Le Mans		France	72015
106	Novartis Investigative Site	Lille Cedex		France	59020
107	Novartis Investigative Site	Lille		France	59037
108	Novartis Investigative Site	Lorient cedex		France	56322
109	Novartis Investigative Site	Lyon Cedex 08		France	69373
110	Novartis Investigative Site	Marseille cedex		France	13008
111	Novartis Investigative Site	Metz Cedex 03		France	57085
112	Novartis Investigative Site	Mont de Marsan		France	40024
113	Novartis Investigative Site	Montpellier cedex 5		France	34298
114	Novartis Investigative Site	Montpellier		France	34070
115	Novartis Investigative Site	Mougins Cedex 2		France	06250
116	Novartis Investigative Site	Nancy		France	54100
117	Novartis Investigative Site	Nantes Cedex 2		France	44277
118	Novartis Investigative Site	Nice Cedex 2		France	06189
119	Novartis Investigative Site	Nimes		France	30907
120	Novartis Investigative Site	Orleans		France	45100
121	Novartis Investigative Site	Paris cedex 05		France	75248
122	Novartis Investigative Site	Paris Cedex 10		France	75475
123	Novartis Investigative Site	Paris Cedex 20		France	75970
124	Novartis Investigative Site	Paris Cedex 4		France	75181
125	Novartis Investigative Site	Paris		France	75012
126	Novartis Investigative Site	Paris		France	75014
127	Novartis Investigative Site	Perigueux Cedex		France	24004
128	Novartis Investigative Site	Perin Sur Mer		France	22190
129	Novartis Investigative Site	Pierre-Benite Cedex		France	69495
130	Novartis Investigative Site	Reims Cedex		France	51056
131	Novartis Investigative Site	Rouen		France	76000
132	Novartis Investigative Site	Saint-Herblain		France	44805
133	Novartis Investigative Site	Saint-Priest en Jarez		France	42271
134	Novartis Investigative Site	Strasbourg Cedex		France	67091
135	Novartis Investigative Site	Strasbourg		France	67000
136	Novartis Investigative Site	Suresnes		France	92151
137	Novartis Investigative Site	Thonon-les-Bains		France	74203
138	Novartis Investigative Site	Vandoeuvre-Les-Nancy		France	54511
139	Novartis Investigative Site	Esslingen	Baden-Wuerttemberg	Germany	73730
140	Novartis Investigative Site	Freiburg	Baden-Wuerttemberg	Germany	79098
141	Novartis Investigative Site	Freiburg	Baden-Wuerttemberg	Germany	79106
142	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg	Germany	76133
143	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg	Germany	76135
144	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg	Germany	68167
145	Novartis Investigative Site	Mutlangen	Baden-Wuerttemberg	Germany	73557
146	Novartis Investigative Site	Reutlingen	Baden-Wuerttemberg	Germany	72764
147	Novartis Investigative Site	Schwaebisch Hall	Baden-Wuerttemberg	Germany	74523
148	Novartis Investigative Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
149	Novartis Investigative Site	Ulm	Baden-Wuerttemberg	Germany	89075
150	Novartis Investigative Site	Bayreuth	Bayern	Germany	95445
151	Novartis Investigative Site	Coburg	Bayern	Germany	96450
152	Novartis Investigative Site	Deggendorf	Bayern	Germany	94469
153	Novartis Investigative Site	Ebersberg	Bayern	Germany	85560
154	Novartis Investigative Site	Eggenfelden	Bayern	Germany	84307
155	Novartis Investigative Site	Fuerth	Bayern	Germany	90766
156	Novartis Investigative Site	Muenchen	Bayern	Germany	80637
157	Novartis Investigative Site	Muenchen	Bayern	Germany	81377
158	Novartis Investigative Site	Muenchen	Bayern	Germany	81675
159	Novartis Investigative Site	Schweinfurt	Bayern	Germany	97422
160	Novartis Investigative Site	Darmstadt	Hessen	Germany	64283
161	Novartis Investigative Site	Frankfurt am Main	Hessen	Germany	60590
162	Novartis Investigative Site	Frankfurt	Hessen	Germany	65929
163	Novartis Investigative Site	Fulda	Hessen	Germany	36043
164	Novartis Investigative Site	Kassel	Hessen	Germany	34125
165	Novartis Investigative Site	Lich	Hessen	Germany	35423
166	Novartis Investigative Site	Limburg	Hessen	Germany	65549
167	Novartis Investigative Site	Marburg	Hessen	Germany	35043
168	Novartis Investigative Site	Offenbach	Hessen	Germany	63065
169	Novartis Investigative Site	Offenbach	Hessen	Germany	63069
170	Novartis Investigative Site	Wiesbaden	Hessen	Germany	65189
171	Novartis Investigative Site	Wiesbaden	Hessen	Germany	65199
172	Novartis Investigative Site	Greifswald	Mecklenburg-Vorpommern	Germany	17475
173	Novartis Investigative Site	Rostock	Mecklenburg-Vorpommern	Germany	18059
174	Novartis Investigative Site	Braunschweig	Niedersachsen	Germany	38100
175	Novartis Investigative Site	Cuxhaven	Niedersachsen	Germany	27474
176	Novartis Investigative Site	Georgsmarienhuette	Niedersachsen	Germany	49124
177	Novartis Investigative Site	Gifhorn	Niedersachsen	Germany	38518
178	Novartis Investigative Site	Goettingen	Niedersachsen	Germany	37075
179	Novartis Investigative Site	Goslar	Niedersachsen	Germany	38642
180	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30169
181	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30177
182	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30625
183	Novartis Investigative Site	Hildesheim	Niedersachsen	Germany	31134
184	Novartis Investigative Site	Leer	Niedersachsen	Germany	26789
185	Novartis Investigative Site	Lueneburg	Niedersachsen	Germany	21339
186	Novartis Investigative Site	Oldenburg	Niedersachsen	Germany	26121
187	Novartis Investigative Site	Salzgitter	Niedersachsen	Germany	38226
188	Novartis Investigative Site	Wolfsburg	Niedersachsen	Germany	38440
189	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	053123
190	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53111
191	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53113
192	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53127
193	Novartis Investigative Site	Detmold	Nordrhein-Westfalen	Germany	32756
194	Novartis Investigative Site	Dortmund	Nordrhein-Westfalen	Germany	44137
195	Novartis Investigative Site	Duesseldorf	Nordrhein-Westfalen	Germany	40225
196	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45122
197	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45136
198	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45147
199	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
200	Novartis Investigative Site	Neuss	Nordrhein-Westfalen	Germany	41464
201	Novartis Investigative Site	Troisdorf	Nordrhein-Westfalen	Germany	53840
202	Novartis Investigative Site	Viersen	Nordrhein-Westfalen	Germany	41747
203	Novartis Investigative Site	Mainz	Rheinland-Pfalz	Germany	55131
204	Novartis Investigative Site	Trier	Rheinland-Pfalz	Germany	54290
205	Novartis Investigative Site	Halle	Sachsen-Anhalt	Germany	06120
206	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt	Germany	39108
207	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt	Germany	39110
208	Novartis Investigative Site	Quedlinburg	Sachsen-Anhalt	Germany	06484
209	Novartis Investigative Site	Salzwedel	Sachsen-Anhalt	Germany	29410
210	Novartis Investigative Site	Chemnitz	Sachsen	Germany	09116
211	Novartis Investigative Site	Dresden	Sachsen	Germany	01127
212	Novartis Investigative Site	Dresden	Sachsen	Germany	01307
213	Novartis Investigative Site	Leipzg	Sachsen	Germany	04109
214	Novartis Investigative Site	Radebeul	Sachsen	Germany	01445
215	Novartis Investigative Site	Zwickau	Sachsen	Germany	08060
216	Novartis Investigative Site	Flensburg	Schleswig-Holstein	Germany	24939
217	Novartis Investigative Site	Kiel	Schleswig-Holstein	Germany	24105
218	Novartis Investigative Site	Luebeck	Schleswig-Holstein	Germany	23538
219	Novartis Investigative Site	Gera	Thueringen	Germany	07548
220	Novartis Investigative Site	Nordhausen	Thueringen	Germany	99734
221	Novartis Investigative Site	Suhl	Thueringen	Germany	98527
222	Novartis Investigative Site	Berlin		Germany	10367
223	Novartis Investigative Site	Berlin		Germany	12683
224	Novartis Investigative Site	Berlin		Germany	13353
225	Novartis Investigative Site	Berlin		Germany	13589
226	Novartis Investigative Site	Hamburg		Germany	20095
227	Novartis Investigative Site	Hamburg		Germany	20246
228	Novartis Investigative Site	Hamburg		Germany	22087
229	Novartis Investigative Site	Hong Kong		Hong Kong
230	Novartis Investigative Site	Kowloon		Hong Kong
231	Novartis Investigative Site	Dublin		Ireland	4
232	Novartis Investigative Site	Dublin		Ireland	7
233	Novartis Investigative Site	Dublin		Ireland	8
234	Novartis Investigative Site	Dublin		Ireland	9
235	Novartis Investigative Site	Waterford		Ireland
236	Novartis Investigative Site	Wilton, Cork		Ireland
237	Novartis Investigative Site	Potenza	Basilicata	Italy	85100
238	Novartis Investigative Site	Avellino	Campania	Italy	83100
239	Novartis Investigative Site	Napoli	Campania	Italy	80131
240	Novartis Investigative Site	Bologna	Emilia-Romagna	Italy	40138
241	Novartis Investigative Site	Bologna	Emilia-Romagna	Italy	40139
242	Novartis Investigative Site	Carpi (MO)	Emilia-Romagna	Italy	41012
243	Novartis Investigative Site	Faenza (RA)	Emilia-Romagna	Italy	48018
244	Novartis Investigative Site	Reggio Emilia	Emilia-Romagna	Italy	42100
245	Novartis Investigative Site	Aviano (PN)	Friuli-Venezia-Giulia	Italy	33081
246	Novartis Investigative Site	Roma	Lazio	Italy	00144
247	Novartis Investigative Site	Roma	Lazio	Italy	00168
248	Novartis Investigative Site	Roma	Lazio	Italy	00186
249	Novartis Investigative Site	Brescia	Lombardia	Italy
250	Novartis Investigative Site	Como	Lombardia	Italy	22100
251	Novartis Investigative Site	Milano	Lombardia	Italy	20122
252	Novartis Investigative Site	Milano	Lombardia	Italy	20132
253	Novartis Investigative Site	Milano	Lombardia	Italy	20133
254	Novartis Investigative Site	Milano	Lombardia	Italy	20141
255	Novartis Investigative Site	Milano	Lombardia	Italy	20162
256	Novartis Investigative Site	Monza	Lombardia	Italy	20052
257	Novartis Investigative Site	Sondrio	Lombardia	Italy	23100
258	Novartis Investigative Site	Varese	Lombardia	Italy	21100
259	Novartis Investigative Site	Campobasso	Molise	Italy	86100
260	Novartis Investigative Site	Torino	Piemonte	Italy	10126
261	Novartis Investigative Site	Torino	Piemonte	Italy	10128
262	Novartis Investigative Site	Bari	Puglia	Italy	70124
263	Novartis Investigative Site	Palermo	Sicilia	Italy	90146
264	Novartis Investigative Site	Perugia	Umbria	Italy	06132
265	Novartis Investigative Site	Vicenza	Veneto	Italy	36100
266	Novartis Investigative Site	Ehime		Japan	791-0280
267	Novartis Investigative Site	Fukuoka		Japan	811-1395
268	Novartis Investigative Site	Hiroshima		Japan	734-8551
269	Novartis Investigative Site	Hiroshima		Japan	737-0023
270	Novartis Investigative Site	Hokkaido		Japan	060-8648
271	Novartis Investigative Site	Iwate		Japan	020-8505
272	Novartis Investigative Site	Kagoshima		Japan	890-8760
273	Novartis Investigative Site	Miyagi		Japan	980-8574
274	Novartis Investigative Site	Osaka		Japan	589-8511
275	Novartis Investigative Site	Saitama		Japan	350-1298
276	Novartis Investigative Site	Tokyo		Japan	104-0045
277	Novartis Investigative Site	Tokyo		Japan	105-8471
278	Novartis Investigative Site	Tokyo		Japan	125-8506
279	Novartis Investigative Site	Tokyo		Japan	160-8582
280	Novartis Investigative Site	Tottori		Japan	683-8504
281	Novartis Investigative Site	Goyang-si, Gyeonggi-do		Korea, Republic of	410-769
282	Novartis Investigative Site	Kangnam-Ku ,Seoul		Korea, Republic of	(135-702)
283	Novartis Investigative Site	Seoul		Korea, Republic of	03080
284	Novartis Investigative Site	Seoul		Korea, Republic of	135-710
285	Novartis Investigative Site	Seoul		Korea, Republic of	138-736
286	Novartis Investigative Site	Bergen		Norway	5021
287	Novartis Investigative Site	Oslo		Norway	0310
288	Novartis Investigative Site	Stavanger		Norway	4011
289	Novartis Investigative Site	Tromso		Norway	9038
290	Novartis Investigative Site	Alcorcon (Madrid)		Spain	28922
291	Novartis Investigative Site	Barcelona		Spain	080018
292	Novartis Investigative Site	Barcelona		Spain	08003
293	Novartis Investigative Site	Barcelona		Spain	08025
294	Novartis Investigative Site	Barcelona		Spain	08907
295	Novartis Investigative Site	Cartagena (Murcia)		Spain	30203
296	Novartis Investigative Site	Elche		Spain	03203
297	Novartis Investigative Site	Lerida		Spain	25198
298	Novartis Investigative Site	Madrid		Spain	28007
299	Novartis Investigative Site	Madrid		Spain	28033
300	Novartis Investigative Site	Madrid		Spain	28034
301	Novartis Investigative Site	Madrid		Spain	28046
302	Novartis Investigative Site	Madrid		Spain	28050
303	Novartis Investigative Site	Murcia (El Palmar)		Spain	30120
304	Novartis Investigative Site	Palma de Mallorca		Spain	07198
305	Novartis Investigative Site	Pamplona		Spain	31008
306	Novartis Investigative Site	Sabadell (Barcelona)		Spain	08208
307	Novartis Investigative Site	San Sebastian		Spain	20014
308	Novartis Investigative Site	Santiago de Compostela		Spain	15706
309	Novartis Investigative Site	Terrassa		Spain	08227
310	Novartis Investigative Site	Valencia		Spain	46009
311	Novartis Investigative Site	Valencia		Spain	46014
312	Novartis Investigative Site	Zaragoza		Spain	50009
313	Novartis Investigative Site	Linkoping		Sweden	SE-581 85
314	Novartis Investigative Site	Lund		Sweden	SE-221 85
315	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
316	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
317	Novartis Investigative Site	Taipei		Taiwan	104
318	Novartis Investigative Site	Taipei		Taiwan	112

Sponsors and Collaborators

• Novartis Pharmaceuticals
• GlaxoSmithKline

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 13, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00866697
• Other Study ID Numbers: 110655; 2008-004672-50; CPZP034C2301
• First Posted: Mar 20, 2009
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: fallopian tube cancer; pazopanib; anti-angiogenesis; ovarian cancer; primary peritoneal cancer; tyrosine kinase inhibitors; gynecologic cancer
• Additional relevant MeSH terms: Ovarian Neoplasms

Study Results

Participant Flow

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	254	244
NOT COMPLETED	214	228

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 Participants	468	472	940
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.8 (10.83)	55.8 (10.54)	56.3 (10.69)
Sex: Female, Male (Count of Participants)
Female	468 100%	472 100%	940 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of 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%	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.
Measure Participants	468	472
Median (95% Confidence Interval) [months]	12.3	17.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib 800 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.766
	Confidence Interval	(2-Sided) 95%; 0.643 to 0.911
	Parameter Dispersion	Type: Value:
	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.
Measure Participants	468	472
Median (95% Confidence Interval) [months]	64.0	59.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pazopanib 800 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6431
	Comments
	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
	Parameter Dispersion	Type: Value:
	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.
Measure Participants	468	472
deaths	253 54.1%	241 51.1%
censored, follow up ended (no deaths)	215 45.9%	231 48.9%

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.
Measure Participants	468	472
Median (95% Confidence Interval) [months]	11.9	16.8

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.
Measure Participants	468	472
Number [percentage of participants]	NA NaN	NA NaN

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.
Measure Participants	393	293
Week 13	0.58 (0.821)	-3.82 (0.950)
Month 7	0.95 (0.962)	-4.65 (1.139)
Month 10	1.98 (0.972)	-4.28 (1.115)
Month 13	0.65 (1.200)	-1.80 (1.398)
Month 16	1.39 (1.370)	0.96 (1.702)
Month 25	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.
Measure Participants	378	291
Week 13	9.92 (1.110)	4.24 (1.263)
Month 7	12.10 (1.203)	4.94 (1.385)
Month 10	14.31 (1.310)	8.54 (1.467)
Month 13	15.45 (1.388)	10.07 (1.589)
Month 16	15.81 (1.668)	13.25 (2.013)
Month 25	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.
Measure Participants	386	297
Week 13	7.18 (1.063)	2.99 (1.210)
Month 7	7.88 (1.141)	4.26 (1.319)
Month 10	8.12 (1.319)	4.65 (1.482)
Month 13	8.54 (1.421)	4.34 (1.616)
Month 16	7.68 (1.633)	6.21 (1.941)
Month 25	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.
Measure Participants	388	297
Week 13	-3.34 (1.038)	-5.22 (1.184)
Month 7	-6.12 (1.104)	-5.20 (1.270)
Month 10	-7.85 (1.209)	-5.11 (1.361)
Month 13	-8.76 (1.301)	-6.37 (1.499)
Month 16	-8.66 (1.456)	-8.65 (1.745)
Month 25	-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.
Measure Participants	388	289
Week 13	0.93 (0.673)	6.62 (0.777)
Month 7	2.36 (0.831)	11.11 (0.967)
Month 10	2.74 (0.957)	11.33 (0.957)
Month 13	3.64 (1.027)	12.29 (1.181)
Month 16	3.69 (1.251)	8.11 (1.503)
Month 25	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.
Measure Participants	398	299
Week 13	-0.86 (1.026)	-0.95 (1.177)
Month 7	-0.38 (1.185)	1.29 (1.371)
Month 10	-2.17 (1.299)	0.83 (1.470)
Month 13	-2.77 (1.396)	-0.74 (1.594)
Month 16	-0.41 (1.610)	1.09 (1.920)
Month 25	-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.
Measure Participants	0	0

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.
Measure Participants	0	0

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.
Measure Participants	371	288
Week 13	1.35 (0.876)	1.20 (0.993)
Month 7	3.00 (0.929)	1.69 (1.076)
Month 10	3.68 (1.048)	0.98 (1.179)
Month 13	2.92 (1.194)	2.49 (1.369)
Month 16	3.30 (1.219)	3.51 (1.451)
Month 25	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.
Measure Participants	376	293
Week 13	0.00 (0.009)	-0.04 (0.010)
Month 7	0.00 (0.010)	-0.04 (0.012)
Month 10	0.01 (0.011)	-0.04 (0.012)
Month 13	0.01 (0.011)	-0.01 (0.013)
Month 16	-0.00 (0.014)	0.03 (0.017)
Month 25	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.
Measure Participants	461	477
Hypertension, G2	52 11.1%	95 20.1%
Hypertension, G3	25 5.3%	139 29.4%
Hypertension, G4	0 0%	0 0%
Diarrhoea, G2	22 4.7%	97 20.6%
Diarrhoea, G3	5 1.1%	38 8.1%
Diarrhoea, G4	0 0%	1 0.2%
Nausea, G2	15 3.2%	42 8.9%
Nausea, G3	0 0%	4 0.8%
Nausea, G4	0 0%	0 0%
Headache, G2	6 1.3%	36 7.6%
Headache, G3	3 0.6%	8 1.7%
Headache, G4	0 0%	0 0%
Fatigue, G2	19 4.1%	42 8.9%
Fatigue, G3	1 0.2%	7 1.5%
Fatigue, G4	0 0%	0 0%
Neutropenia, G2	17 3.6%	51 10.8%
Neutropenia, G3	2 0.4%	29 6.1%
Neutropenia, G4	2 0.4%	3 0.6%
Dysgeusia, G2	0 0%	16 3.4%
Dysgeusia, G3	0 0%	0 0%
Dysgeusia, G4	0 0%	0 0%
Abdominal pain, G2	21 4.5%	26 5.5%
Abdominal pain, G3	5 1.1%	5 1.1%
Abdominal pain, G4	0 0%	0 0%
Alanine aminotransferase increased, G2	4 0.9%	22 4.7%
Alanine aminotransferase increased, G3	0 0%	24 5.1%
Alanine aminotransferase increased, G4	1 0.2%	4 0.8%
Hair color changes, G2	0 0%	13 2.8%
Hair color changes, G3	0 0%	0 0%
Hair color changes, G4	0 0%	0 0%
Decreased appetite, G2	2 0.4%	19 4%
Decreased appetite, G3	0 0%	1 0.2%
Decreased appetite, G4	0 0%	0 0%
Vomiting, G2	8 1.7%	21 4.4%
Vomiting, G3	1 0.2%	4 0.8%
Vomiting, G4	0 0%	0 0%
Aspartate aminotransferase increased, G2	3 0.6%	22 4.7%
Aspartate aminotransferase increased, G3	0 0%	10 2.1%
Aspartate aminotransferase increased, G4	1 0.2%	3 0.6%
Arthralgia, G2	13 2.8%	19 4%
Arthralgia, G3	3 0.6%	5 1.1%
Arthralgia, G4	0 0%	0 0%
Abdominal pain upper, G2	3 0.6%	20 4.2%
Abdominal pain upper, G3	1 0.2%	1 0.2%
Abdominal pain upper, G4	0 0%	1 0.2%
Asthenia, G2	8 1.7%	28 5.9%
Asthenia, G3	0 0%	6 1.3%
Asthenia, G4	0 0%	0 0%
Palmar-plantar erythrodysaesthesia syndrome, G2	2 0.4%	42 8.9%
Palmar-plantar erythrodysaesthesia syndrome, G3	1 0.2%	9 1.9%
Palmar-plantar erythrodysaesthesia syndrome, G4	0 0%	0 0%
Thrombocytopenia, G2	1 0.2%	15 3.2%
Thrombocytopenia, G3	1 0.2%	6 1.3%
Thrombocytopenia, G4	2 0.4%	3 0.6%
Hypothyroidism, G2	9 1.9%	19 4%
Hypothyroidism, G3	0 0%	0 0%
Hypothyroidism, G4	0 0%	0 0%
Constipation, G2	20 4.3%	12 2.5%
Constipation, G3	1 0.2%	1 0.2%
Constipation, G4	0 0%	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.
Measure Participants	456	466
Hemoglobin, Any grade increase	44 9.4%	68 14.4%
Hemoglobin, Increase to Grade 3	0 0%	0 0%
Hemoglobin, Increase to Grade 4	0 0%	0 0%
Lymphocytes, Any grade increase	75 16%	91 19.3%
Lymphocytes, Increase to Grade 3	1 0.2%	13 2.8%
Lymphocytes, Increase to Grade 4	0 0%	0 0%
Neutrophils, Any grade increase	80 17.1%	236 50%
Neutrophils, Increase to Grade 3	2 0.4%	44 9.3%
Neutrophils, Increase to Grade 4	0 0%	5 1.1%
Platelets, Any grade increase	25 5.3%	167 35.4%
Platelets, Increase to Grade 3	1 0.2%	8 1.7%
Platelets, Increase to Grade 4	1 0.2%	4 0.8%
WBC count, Any grade increase	77 16.5%	236 50%
WBC count, Increase to Grade 3	0 0%	11 2.3%
WBC count, Increase to Grade 4	0 0%	1 0.2%

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.
Measure Participants	456	465
Albumin, Any grade increase	33 7.1%	50 10.6%
Albumin, Increase to Grade 3	0 0%	0 0%
Albumin, Increase to Grade 4	0 0%	0 0%
Creatinine, Any grade increase	27 5.8%	42 8.9%
Creatinine, Increase to Grade 3	0 0%	1 0.2%
Creatinine, Increase to Grade 4	0 0%	0 0%
Hypercalcemia, Any grade increase	33 7.1%	16 3.4%
Hypercalcemia, Increase to Grade 3	0 0%	0 0%
Hypercalcemia, Increase to Grade 4	0 0%	0 0%
Hyperglycemia, Any grade increase	117 25%	128 27.1%
Hyperglycemia, Increase to Grade 3	10 2.1%	2 0.4%
Hyperglycemia, Increase to Grade 4	0 0%	0 0%
Hyperkalemia, Any grade increase	39 8.3%	38 8.1%
Hyperkalemia, Increase to Grade 3	2 0.4%	1 0.2%
Hyperkalemia, Increase to Grade 4	0 0%	2 0.4%
Hypermagnesemia, Any grade increase	11 2.4%	20 4.2%
Hypermagnesemia, Increase to Grade 3	1 0.2%	6 1.3%
Hypermagnesemia, Increase to Grade 4	1 0.2%	0 0%
Hypernatremia, Any grade increase	26 5.6%	25 5.3%
Hypernatremia, Increase to Grade 3	0 0%	0 0%
Hypernatremia, Increase to Grade 4	0 0%	0 0%
Hypocalcemia, Any grade increase	21 4.5%	52 11%
Hypocalcemia, Increase to Grade 3	0 0%	2 0.4%
Hypocalcemia, Increase to Grade 4	0 0%	0 0%
Hypoglycemia, Any grade increase	25 5.3%	41 8.7%
Hypoglycemia, Increase to Grade 3	2 0.4%	0 0%
Hypoglycemia, Increase to Grade 4	2 0.4%	2 0.4%
Hypokalemia, Any grade increase	31 6.6%	40 8.5%
Hypokalemia, Increase to Grade 3	1 0.2%	2 0.4%
Hypokalemia, Increase to Grade 4	1 0.2%	0 0%
Hypomagnesemia, Any grade increase	55 11.8%	65 13.8%
Hypomagnesemia, Increase to Grade 3	3 0.6%	1 0.2%
Hypomagnesemia, Increase to Grade 4	0 0%	2 0.4%
Hyponatremia, Any grade increase	37 7.9%	45 9.5%
Hyponatremia, Increase to Grade 3	5 1.1%	9 1.9%
Hyponatremia, Increase to Grade 4	0 0%	0 0%
Phosphate, Any grade increase	33 7.1%	24 5.1%
Phosphate, Increase to Grade 3	4 0.9%	0 0%
Phosphate, Increase to Grade 4	0 0%	1 0.2%

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.
Measure Participants	42	157
5 <TSH <=10 MU/L	34 7.3%	94 19.9%
10 <TSH <=20 MU/L	4 0.9%	36 7.6%
TSH >20 MU/L	4 0.9%	27 5.7%

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.
Measure Participants	461	477
All Treated Population	461 98.5%	477 101.1%
Total deaths	252 53.8%	245 51.9%
On-treatment Deaths - occurring less than or equal to 28 days from last dose	0 0%	3 0.6%

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.
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/461 (0%)		3/477 (0.6%)
Serious Adverse Events
	Placebo		Pazopanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/461 (11.1%)		121/477 (25.4%)
Blood and lymphatic system disorders
Febrile neutropenia	1/461 (0.2%)		2/477 (0.4%)
Neutropenia	0/461 (0%)		2/477 (0.4%)
Thrombocytopenia	1/461 (0.2%)		4/477 (0.8%)
Cardiac disorders
Acute coronary syndrome	1/461 (0.2%)		0/477 (0%)
Angina pectoris	0/461 (0%)		1/477 (0.2%)
Bradycardia	0/461 (0%)		1/477 (0.2%)
Cardiac failure	0/461 (0%)		1/477 (0.2%)
Cardiomyopathy	0/461 (0%)		1/477 (0.2%)
Coronary artery disease	0/461 (0%)		1/477 (0.2%)
Coronary artery insufficiency	1/461 (0.2%)		0/477 (0%)
Myocardial infarction	0/461 (0%)		2/477 (0.4%)
Myocardial ischaemia	0/461 (0%)		1/477 (0.2%)
Sinus bradycardia	0/461 (0%)		1/477 (0.2%)
Ventricular tachycardia	0/461 (0%)		1/477 (0.2%)
Ear and labyrinth disorders
Vertigo	0/461 (0%)		1/477 (0.2%)
Eye disorders
Vitreous detachment	0/461 (0%)		1/477 (0.2%)
Vitreous floaters	0/461 (0%)		1/477 (0.2%)
Vitreous haemorrhage	0/461 (0%)		2/477 (0.4%)
Gastrointestinal disorders
Abdominal mass	1/461 (0.2%)		0/477 (0%)
Abdominal pain	3/461 (0.7%)		3/477 (0.6%)
Abdominal pain lower	0/461 (0%)		1/477 (0.2%)
Abdominal pain upper	1/461 (0.2%)		0/477 (0%)
Anal haemorrhage	1/461 (0.2%)		0/477 (0%)
Ascites	1/461 (0.2%)		1/477 (0.2%)
Constipation	1/461 (0.2%)		1/477 (0.2%)
Diarrhoea	2/461 (0.4%)		3/477 (0.6%)
Duodenitis	0/461 (0%)		1/477 (0.2%)
Enterocele	0/461 (0%)		1/477 (0.2%)
Gastric ulcer perforation	0/461 (0%)		2/477 (0.4%)
Gastrointestinal haemorrhage	0/461 (0%)		1/477 (0.2%)
Ileus	0/461 (0%)		2/477 (0.4%)
Intestinal obstruction	3/461 (0.7%)		3/477 (0.6%)
Large intestinal obstruction	1/461 (0.2%)		0/477 (0%)
Nausea	1/461 (0.2%)		2/477 (0.4%)
Pancreatitis acute	0/461 (0%)		1/477 (0.2%)
Rectal haemorrhage	0/461 (0%)		1/477 (0.2%)
Small intestinal obstruction	1/461 (0.2%)		1/477 (0.2%)
Subileus	3/461 (0.7%)		1/477 (0.2%)
Vomiting	2/461 (0.4%)		4/477 (0.8%)
General disorders
Asthenia	1/461 (0.2%)		0/477 (0%)
Fatigue	0/461 (0%)		2/477 (0.4%)
Fibrosis	0/461 (0%)		1/477 (0.2%)
General physical health deterioration	1/461 (0.2%)		4/477 (0.8%)
Hernia	1/461 (0.2%)		2/477 (0.4%)
Ill-defined disorder	1/461 (0.2%)		0/477 (0%)
Influenza like illness	1/461 (0.2%)		0/477 (0%)
Pyrexia	2/461 (0.4%)		9/477 (1.9%)
Hepatobiliary disorders
Cholecystitis	0/461 (0%)		1/477 (0.2%)
Cholecystitis acute	0/461 (0%)		1/477 (0.2%)
Hepatocellular injury	0/461 (0%)		1/477 (0.2%)
Hepatotoxicity	0/461 (0%)		3/477 (0.6%)
Immune system disorders
Cytokine release syndrome	0/461 (0%)		1/477 (0.2%)
Drug hypersensitivity	0/461 (0%)		1/477 (0.2%)
Hypersensitivity	0/461 (0%)		2/477 (0.4%)
Sarcoidosis	1/461 (0.2%)		0/477 (0%)
Infections and infestations
Bronchitis	1/461 (0.2%)		0/477 (0%)
Erysipelas	1/461 (0.2%)		0/477 (0%)
Gastroenteritis	1/461 (0.2%)		1/477 (0.2%)
Gastroenteritis norovirus	0/461 (0%)		1/477 (0.2%)
Infected lymphocele	1/461 (0.2%)		1/477 (0.2%)
Infectious colitis	1/461 (0.2%)		0/477 (0%)
Infectious pleural effusion	0/461 (0%)		1/477 (0.2%)
Localised infection	1/461 (0.2%)		0/477 (0%)
Pelvic abscess	0/461 (0%)		1/477 (0.2%)
Pharyngotonsillitis	0/461 (0%)		1/477 (0.2%)
Pneumonia	0/461 (0%)		2/477 (0.4%)
Pyelonephritis	0/461 (0%)		1/477 (0.2%)
Respiratory tract infection	0/461 (0%)		1/477 (0.2%)
Subcutaneous abscess	0/461 (0%)		1/477 (0.2%)
Tooth abscess	1/461 (0.2%)		0/477 (0%)
Urinary tract infection	3/461 (0.7%)		0/477 (0%)
Injury, poisoning and procedural complications
Contusion	1/461 (0.2%)		0/477 (0%)
Fall	1/461 (0.2%)		0/477 (0%)
Incisional hernia	1/461 (0.2%)		0/477 (0%)
Overdose	1/461 (0.2%)		0/477 (0%)
Procedural complication	0/461 (0%)		1/477 (0.2%)
Thermal burn	0/461 (0%)		1/477 (0.2%)
Tibia fracture	1/461 (0.2%)		0/477 (0%)
Upper limb fracture	1/461 (0.2%)		0/477 (0%)
Wound dehiscence	0/461 (0%)		1/477 (0.2%)
Investigations
Alanine aminotransferase increased	0/461 (0%)		18/477 (3.8%)
Aspartate aminotransferase increased	0/461 (0%)		7/477 (1.5%)
Blood bilirubin increased	0/461 (0%)		2/477 (0.4%)
Blood lactate dehydrogenase increased	0/461 (0%)		1/477 (0.2%)
Ejection fraction decreased	0/461 (0%)		1/477 (0.2%)
Electrocardiogram QT prolonged	1/461 (0.2%)		0/477 (0%)
Electrocardiogram abnormal	0/461 (0%)		1/477 (0.2%)
Gamma-glutamyltransferase increased	0/461 (0%)		2/477 (0.4%)
Hepatic enzyme increased	0/461 (0%)		5/477 (1%)
Liver function test abnormal	0/461 (0%)		1/477 (0.2%)
Neutrophil count decreased	0/461 (0%)		1/477 (0.2%)
Platelet count decreased	0/461 (0%)		1/477 (0.2%)
Transaminases increased	0/461 (0%)		3/477 (0.6%)
Metabolism and nutrition disorders
Decreased appetite	0/461 (0%)		1/477 (0.2%)
Dehydration	0/461 (0%)		1/477 (0.2%)
Hypoglycaemia	0/461 (0%)		1/477 (0.2%)
Hypokalaemia	1/461 (0.2%)		0/477 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/461 (0%)		1/477 (0.2%)
Intervertebral disc protrusion	0/461 (0%)		1/477 (0.2%)
Musculoskeletal chest pain	0/461 (0%)		1/477 (0.2%)
Myalgia intercostal	0/461 (0%)		1/477 (0.2%)
Rheumatoid arthritis	1/461 (0.2%)		0/477 (0%)
Rotator cuff syndrome	1/461 (0.2%)		0/477 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign	1/461 (0.2%)		0/477 (0%)
Intraductal proliferative breast lesion	1/461 (0.2%)		0/477 (0%)
Malignant lymphoma unclassifiable low grade	1/461 (0.2%)		0/477 (0%)
Malignant neoplasm of unknown primary site	0/461 (0%)		1/477 (0.2%)
Metastases to abdominal cavity	0/461 (0%)		1/477 (0.2%)
Squamous cell carcinoma of skin	1/461 (0.2%)		0/477 (0%)
Thyroid adenoma	0/461 (0%)		1/477 (0.2%)
Ulcerated haemangioma	0/461 (0%)		1/477 (0.2%)
Nervous system disorders
Cranial nerve disorder	1/461 (0.2%)		0/477 (0%)
Headache	0/461 (0%)		2/477 (0.4%)
Intercostal neuralgia	0/461 (0%)		1/477 (0.2%)
Ischaemic stroke	0/461 (0%)		1/477 (0.2%)
Migraine	0/461 (0%)		2/477 (0.4%)
Paraesthesia	0/461 (0%)		1/477 (0.2%)
Posterior reversible encephalopathy syndrome	0/461 (0%)		1/477 (0.2%)
Presyncope	0/461 (0%)		1/477 (0.2%)
Seizure	0/461 (0%)		1/477 (0.2%)
Transverse sinus thrombosis	0/461 (0%)		1/477 (0.2%)
Product Issues
Device breakage	1/461 (0.2%)		0/477 (0%)
Renal and urinary disorders
Haematuria	0/461 (0%)		1/477 (0.2%)
Hydronephrosis	2/461 (0.4%)		0/477 (0%)
Urinary retention	1/461 (0.2%)		0/477 (0%)
Urinary tract obstruction	0/461 (0%)		1/477 (0.2%)
Reproductive system and breast disorders
Female genital tract fistula	0/461 (0%)		1/477 (0.2%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/461 (0%)		1/477 (0.2%)
Pleural effusion	1/461 (0.2%)		1/477 (0.2%)
Pulmonary embolism	0/461 (0%)		2/477 (0.4%)
Skin and subcutaneous tissue disorders
Drug eruption	0/461 (0%)		1/477 (0.2%)
Erythema multiforme	0/461 (0%)		1/477 (0.2%)
Palmar-plantar erythrodysaesthesia syndrome	0/461 (0%)		2/477 (0.4%)
Rash	0/461 (0%)		1/477 (0.2%)
Vascular disorders
Arterial thrombosis	0/461 (0%)		1/477 (0.2%)
Hypertension	0/461 (0%)		8/477 (1.7%)
Hypertensive crisis	0/461 (0%)		4/477 (0.8%)
Lymphocele	1/461 (0.2%)		0/477 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Pazopanib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	381/461 (82.6%)		462/477 (96.9%)
Blood and lymphatic system disorders
Leukopenia	5/461 (1.1%)		44/477 (9.2%)
Neutropenia	23/461 (5%)		103/477 (21.6%)
Thrombocytopenia	8/461 (1.7%)		48/477 (10.1%)
Endocrine disorders
Hypothyroidism	15/461 (3.3%)		49/477 (10.3%)
Gastrointestinal disorders
Abdominal pain	94/461 (20.4%)		88/477 (18.4%)
Abdominal pain upper	30/461 (6.5%)		67/477 (14%)
Constipation	72/461 (15.6%)		38/477 (8%)
Diarrhoea	79/461 (17.1%)		252/477 (52.8%)
Dyspepsia	17/461 (3.7%)		24/477 (5%)
Nausea	81/461 (17.6%)		174/477 (36.5%)
Stomatitis	7/461 (1.5%)		27/477 (5.7%)
Vomiting	39/461 (8.5%)		71/477 (14.9%)
General disorders
Asthenia	55/461 (11.9%)		66/477 (13.8%)
Fatigue	66/461 (14.3%)		133/477 (27.9%)
Mucosal inflammation	10/461 (2.2%)		32/477 (6.7%)
Infections and infestations
Urinary tract infection	33/461 (7.2%)		32/477 (6.7%)
Viral upper respiratory tract infection	24/461 (5.2%)		27/477 (5.7%)
Investigations
Alanine aminotransferase increased	25/461 (5.4%)		73/477 (15.3%)
Aspartate aminotransferase increased	24/461 (5.2%)		66/477 (13.8%)
Blood alkaline phosphatase increased	3/461 (0.7%)		24/477 (5%)
Blood bilirubin increased	1/461 (0.2%)		29/477 (6.1%)
Blood thyroid stimulating hormone increased	1/461 (0.2%)		32/477 (6.7%)
Neutrophil count decreased	11/461 (2.4%)		36/477 (7.5%)
Platelet count decreased	1/461 (0.2%)		30/477 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	15/461 (3.3%)		79/477 (16.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	68/461 (14.8%)		71/477 (14.9%)
Back pain	38/461 (8.2%)		30/477 (6.3%)
Muscle spasms	20/461 (4.3%)		35/477 (7.3%)
Myalgia	34/461 (7.4%)		45/477 (9.4%)
Pain in extremity	18/461 (3.9%)		38/477 (8%)
Nervous system disorders
Dizziness	22/461 (4.8%)		26/477 (5.5%)
Dysgeusia	13/461 (2.8%)		95/477 (19.9%)
Headache	70/461 (15.2%)		135/477 (28.3%)
Psychiatric disorders
Insomnia	27/461 (5.9%)		24/477 (5%)
Renal and urinary disorders
Proteinuria	8/461 (1.7%)		40/477 (8.4%)
Respiratory, thoracic and mediastinal disorders
Cough	20/461 (4.3%)		24/477 (5%)
Dyspnoea	21/461 (4.6%)		31/477 (6.5%)
Skin and subcutaneous tissue disorders
Hair colour changes	8/461 (1.7%)		95/477 (19.9%)
Palmar-plantar erythrodysaesthesia syndrome	7/461 (1.5%)		61/477 (12.8%)
Rash	22/461 (4.8%)		42/477 (8.8%)
Vascular disorders
Hot flush	29/461 (6.3%)		23/477 (4.8%)
Hypertension	87/461 (18.9%)		256/477 (53.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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