A Clinical Trial Comparing Efficacy And Safety Of Sunitinib And Capecitabine

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00373113
• Collaborator: (none)
• Enrollment: 482
• Locations: 123
• Arms: 2
• Duration (Months): 55
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To compare efficacy and safety of Sunitinib and Capecitabine in subjects with advanced breast cancer who failed both a taxane and an anthracycline chemotherapy regimen or failed with a taxane and for whom further anthracycline therapy is not indicated

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Capecitabine; Drug: Sunitinib malate	Phase 3

Detailed Description

Patient enrollment in this trial was discontinued based on statistical assessment for futility. An independent Data Monitoring Committee found that even if the trial had been allowed to continue, treatment with single agent sunitinib would be unable to demonstrate a statistically significant improvement in the primary endpoint of progression-free survival compared with single agent capecitabine in the study population. Pfizer notified clinical trial investigators involved in the study and regulatory agencies of these findings on 25Mar2009. Patients receiving sunitinib will be allowed to receive capecitabine or enter an extension trial if they are receiving clinical benefit from continued sunitinib therapy. There were no safety concerns leading to the decision to terminate the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 482 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized, Multi Center Study Of Sunitinib Malate (SU 011248) Or Capecitabine In Subjects With Advanced Breast Cancer Who Failed Both A Taxane And An Anthracycline Chemotherapy Regimen Or Failed With A Taxane And For Whom Further Anthracycline Therapy Is Not Indicated
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A 1250 mg/m^2, twice daily, for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles	Drug: Capecitabine; 1250 mg/m^2, twice daily, for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles; Other Names: xeloda
Experimental: B 37.5 mg daily, continuous dosing	Drug: Sunitinib malate; 37.5 mg daily, continuous dosing; Other Names: sunitinib

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From time of randomization to every 6 weeks thereafter through 22 months or until death]

   Time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occured first.

Secondary Outcome Measures

1. Time to Tumor Progression (TTP) [From time of randomization to every 6 weeks thereafter through 22 months]

   Time from randomization to first documentation of objective tumor progression.

2. Number of Participants With Overall Response (OR) [From time of randomization to every 6 weeks thereafter through 22 months]

   OR was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.0) for at least 4 weeks, confirmed by repeat tumor assessments. CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to (>=) 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

3. Duration of Response (DR) [From time of randomization to every 6 weeks thereafter through 22 months or death]

   Time from the first documentation of OR (CR or PR) that was subsequently confirmed to the first documentation of tumor progression or death due to any cause. CR was defined as disappearance of all target lesions. PR was defined as a >= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.

4. Time to Tumor Response (TTR) [From time of randomization to every 6 weeks thereafter through 22 months]

   Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target lesions. PR was defined as a >= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.

5. Overall Survival (OS) [From time of randomization until death]

   Average time from randomization to first documentation of death due to any cause.

6. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [From Day 1 of Cycle 1, then odd numbered cycles thereafter]

   EORTC QLQ-C30 scales: functional (physical/role/cognitive/emotional/social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms.

7. EORTC QLQ Breast Cancer Module (BR23) [From Day 1 of Cycle 1, then odd numbered cycles thereafter]

   BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score implied a greater degree of symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• breast adenocarcinoma

• prior treatment with an anthracycline and a taxane either concurrently or sequentially in the neoadjuvant, adjuvant and or/ advanced disease treatment settings. No more than 1 chemotherapy regimen in the advanced setting

Exclusion Criteria:

• Prior treatment with regimens of chemotherapy in the advanced/metastatic disease setting beyond those containing anthracyclines and taxanes or multiple anthracyclines/ taxanes treatments.

• Any prior regimen with capecitabine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bahia Blanca	Prov. de Buenos Aires	Argentina	B8001HXM
2	Pfizer Investigational Site	Viedma	Rio Negro	Argentina	8500
3	Pfizer Investigational Site	Rosario	Santa Fé	Argentina	(2000)
4	Pfizer Investigational Site	Buenos Aires		Argentina	C1034ACO
5	Pfizer Investigational Site	Buenos Aires		Argentina	C1405BCH
6	Pfizer Investigational Site	Cordoba		Argentina	X5000AAI
7	Pfizer Investigational Site	Tucuman		Argentina	T4000IAK
8	Pfizer Investigational Site	Darlinghurst	New South Wales	Australia	2010
9	Pfizer Investigational Site	Herston	Queensland	Australia	4029
10	Pfizer Investigational Site	Adelaide	South Australia	Australia	5000
11	Pfizer Investigational Site	Heidelberg	Victoria	Australia	3084
12	Pfizer Investigational Site	Parkville	Victoria	Australia	3050
13	Pfizer Investigational Site	Perth	Western Australia	Australia	6000
14	Pfizer Investigational Site	Curitiba	PR	Brazil	80530-010
15	Pfizer Investigational Site	Rio de Janeiro	RJ	Brazil	20560-120
16	Pfizer Investigational Site	Porto Alegre	RS	Brazil	90610-000
17	Pfizer Investigational Site	Porto Alegre	RS	Brazil	91350-200
18	Pfizer Investigational Site	São Paulo	SP	Brazil	01246-000
19	Pfizer Investigational Site	São Paulo	SP	Brazil	01509-900
20	Pfizer Investigational Site	Sofia		Bulgaria	1233
21	Pfizer Investigational Site	Sofia		Bulgaria	1527
22	Pfizer Investigational Site	Sofia		Bulgaria	1756
23	Pfizer Investigational Site	Stara Zagora		Bulgaria	6000
24	Pfizer Investigational Site	Halifax	Nova Scotia	Canada	B3H 1V7
25	Pfizer Investigational Site	Halifax	Nova Scotia	Canada	B3H 2Y9
26	Pfizer Investigational Site	Halifax	Nova Scotia	Canada	B3H 3A7
27	Pfizer Investigational Site	London	Ontario	Canada	N6A 4L6
28	Pfizer Investigational Site	Toronto	Ontario	Canada	M4N 3M5
29	Pfizer Investigational Site	Quebec		Canada	G1S 4L8
30	Pfizer Investigational Site	Temuco	IX Región	Chile	4810469
31	Pfizer Investigational Site	Medellin	Antioquia	Colombia
32	Pfizer Investigational Site	Bogotá	Cundinamarca	Colombia
33	Pfizer Investigational Site	Bayonne		France	64100
34	Pfizer Investigational Site	Besancon		France	25030
35	Pfizer Investigational Site	Clermont Ferrand		France	63011
36	Pfizer Investigational Site	Lille		France	59020 Cedex
37	Pfizer Investigational Site	Neuilly Sur Seine		France	92200
38	Pfizer Investigational Site	Nice		France	06100
39	Pfizer Investigational Site	Rennes Cedex		France	35042
40	Pfizer Investigational Site	Berlin		Germany	12200
41	Pfizer Investigational Site	Frankfurt		Germany	60488
42	Pfizer Investigational Site	Freiburg		Germany	79106
43	Pfizer Investigational Site	Jena		Germany	07743
44	Pfizer Investigational Site	Kiel		Germany	24103
45	Pfizer Investigational Site	Leer		Germany	26789
46	Pfizer Investigational Site	Luebeck		Germany	23538
47	Pfizer Investigational Site	Magdeburg		Germany	39130
48	Pfizer Investigational Site	Mainz		Germany	55101
49	Pfizer Investigational Site	Meiningen		Germany	98617
50	Pfizer Investigational Site	Muenchen		Germany	81675
51	Pfizer Investigational Site	Offenburg		Germany	77652
52	Pfizer Investigational Site	Tuebingen		Germany	72076
53	Pfizer Investigational Site	Hong Kong		Hong Kong
54	Pfizer Investigational Site	Kowloon		Hong Kong
55	Pfizer Investigational Site	Tuen Mun		Hong Kong
56	Pfizer Investigational Site	Wan Chai,		Hong Kong
57	Pfizer Investigational Site	Navrangpura / Ahmedabad	Gujarat	India	380 009
58	Pfizer Investigational Site	Bangalore	Karnataka	India	560 078
59	Pfizer Investigational Site	Ludhiana	Punjab	India	141 008
60	Pfizer Investigational Site	Jaipur	Rajasthan	India	302013
61	Pfizer Investigational Site	Lucknow	Uttar Pradesh	India	226003
62	Pfizer Investigational Site	Firenze		Italy	50134
63	Pfizer Investigational Site	Milano		Italy	20162
64	Pfizer Investigational Site	Napoli		Italy	80131
65	Pfizer Investigational Site	Reggio Emilia		Italy	42100
66	Pfizer Investigational Site	Nagoya	Aichi	Japan
67	Pfizer Investigational Site	Matsuyama-shi	Ehime	Japan
68	Pfizer Investigational Site	Kitakyushu-City	Fukuoka	Japan
69	Pfizer Investigational Site	Suita	Osaka	Japan
70	Pfizer Investigational Site	Kita-adachi-gun	Saitama	Japan
71	Pfizer Investigational Site	Bunkyo-ku	Tokyo	Japan
72	Pfizer Investigational Site	Chuo-Ku	Tokyo	Japan
73	Pfizer Investigational Site	Fukuoka		Japan
74	Pfizer Investigational Site	Osaka		Japan
75	Pfizer Investigational Site	Goyang-si	Gyeonggi-do	Korea, Republic of	410-769
76	Pfizer Investigational Site	Daegu		Korea, Republic of	705-717
77	Pfizer Investigational Site	Incheon		Korea, Republic of	400-711
78	Pfizer Investigational Site	Pusan		Korea, Republic of	602-739
79	Pfizer Investigational Site	Seoul		Korea, Republic of	110-744
80	Pfizer Investigational Site	Mexico	DF	Mexico	11000
81	Pfizer Investigational Site	Toluca	Estado de Mexico	Mexico	50180
82	Pfizer Investigational Site	Acapulco	Guerrero	Mexico	39670
83	Pfizer Investigational Site	Morelia	Michoacan	Mexico	58020
84	Pfizer Investigational Site	Ciudad Obregon	Sonora	Mexico	85000
85	Pfizer Investigational Site	Chihuahua		Mexico	31000
86	Pfizer Investigational Site	Puebla		Mexico	72530
87	Pfizer Investigational Site	Lima		Peru	05127
88	Pfizer Investigational Site	Lima		Peru	L 27
89	Pfizer Investigational Site	Quezon City		Philippines	1100
90	Pfizer Investigational Site	Quezon City		Philippines	1102
91	Pfizer Investigational Site	Quezon City		Philippines	1104
92	Pfizer Investigational Site	San Juan City		Philippines	1000
93	Pfizer Investigational Site	Singapore		Singapore	119074
94	Pfizer Investigational Site	Singapore		Singapore	169610
95	Pfizer Investigational Site	Parktown		South Africa	2193
96	Pfizer Investigational Site	Sandton		South Africa	2199
97	Pfizer Investigational Site	Mataro	Barcelona	Spain	08304
98	Pfizer Investigational Site	Sabadell	Barcelona	Spain	08208
99	Pfizer Investigational Site	Santander	Cantabria	Spain	39008
100	Pfizer Investigational Site	Alcorcon	Madrid	Spain	28922
101	Pfizer Investigational Site	Bilbao	Vizcaya	Spain	48013
102	Pfizer Investigational Site	Cordoba		Spain	14004
103	Pfizer Investigational Site	Gerona		Spain	17007
104	Pfizer Investigational Site	Jaen		Spain	23007
105	Pfizer Investigational Site	La Coruña		Spain	15006
106	Pfizer Investigational Site	Las Palmas de Gran Canaria		Spain	35016
107	Pfizer Investigational Site	Madrid		Spain	28033
108	Pfizer Investigational Site	Madrid		Spain	28040
109	Pfizer Investigational Site	Malaga		Spain	29010
110	Pfizer Investigational Site	Salamanca		Spain	37007
111	Pfizer Investigational Site	Changhua		Taiwan	500
112	Pfizer Investigational Site	Kaohsiung		Taiwan	807
113	Pfizer Investigational Site	Tainan		Taiwan	704
114	Pfizer Investigational Site	Taipei		Taiwan	100
115	Pfizer Investigational Site	Taipei		Taiwan	106
116	Pfizer Investigational Site	Taipei		Taiwan	112
117	Pfizer Investigational Site	Taoyuan		Taiwan	333
118	Pfizer Investigational Site	Ankara		Turkey	06100
119	Pfizer Investigational Site	Istanbul		Turkey	34390
120	Pfizer Investigational Site	Cardiff	South Wales	United Kingdom	CF14 2TL
121	Pfizer Investigational Site	London		United Kingdom	SE1 9RT
122	Pfizer Investigational Site	Nottingham		United Kingdom	NG5 1PB
123	Pfizer Investigational Site	Somerset		United Kingdom	BA21 4AT

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00373113
• Other Study ID Numbers: A6181107
• First Posted: Sep 7, 2006
• Last Update Posted: Jun 25, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Pfizer: advanced breast cancer; metastatic breast cancer; treatment resistant; treatment failure
• Additional relevant MeSH terms: Breast Neoplasms; Capecitabine; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 milligrams (mg) daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Period Title: Overall Study
STARTED	238	244
Received Treatment	238	240
COMPLETED	0	0
NOT COMPLETED	238	244

Baseline Characteristics

Arm/Group Title	Sunitinib	Capecitabine	Total
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles	Total of all reporting groups
Overall Participants	238	244	482
Age, Customized (Number) [Number]
18 to 44 years	50 21%	70 28.7%	120 24.9%
45 to 64 years	159 66.8%	129 52.9%	288 59.8%
> = 65 years	29 12.2%	45 18.4%	74 15.4%
Sex/Gender, Customized (Number) [Number]
Female	238 100%	244 100%	482 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occured first.
Time Frame	From time of randomization to every 6 weeks thereafter through 22 months or until death

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: included all participants who were randomized.

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	238	244
Median (95% Confidence Interval) [Months]	2.8	4.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Capecitabine
	Comments	Null hypothesis is that PFS (median=4.2 months) for sunitinib arm equals PFS for capecitabine arm. The study was designed to have 90% power to detect statistical difference in PFS between two treatment groups assuming the hazard ratio (sunitinib/capecitabine) is 0.75 and both arms follow exponential distribution.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	2-sided log-rank test with the same set of stratification factors. The set of stratification factors included those used in the randomization except study sites.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.470
	Confidence Interval	(2-Sided) 95%; 1.156 to 1.869
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was calculated by the stratified Cox proportional hazards model.

2. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	Time from randomization to first documentation of objective tumor progression.
Time Frame	From time of randomization to every 6 weeks thereafter through 22 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	238	244
Median (95% Confidence Interval) [Months]	2.8	4.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Capecitabine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	2-sided log-rank test with the same set of stratification factors that was used in the randomization except study sites.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.516
	Confidence Interval	(2-Sided) 95%; 1.188 to 1.933
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was calculated by the stratified Cox proportional hazards model.

3. Secondary Outcome

Title	Number of Participants With Overall Response (OR)
Description	OR was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.0) for at least 4 weeks, confirmed by repeat tumor assessments. CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to (>=) 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	From time of randomization to every 6 weeks thereafter through 22 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	238	244
Number [Participants]	27 11.3%	40 16.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	11.3
	Confidence Interval	(2-Sided) 95%; 7.6 to 16.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Capecitabine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 95%; 12.0 to 21.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Capecitabine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments
	Method	Pearson Chi-Square Test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.049
	Confidence Interval	(2-Sided) 95%; -11.2 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response (DR)
Description	Time from the first documentation of OR (CR or PR) that was subsequently confirmed to the first documentation of tumor progression or death due to any cause. CR was defined as disappearance of all target lesions. PR was defined as a >= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.
Time Frame	From time of randomization to every 6 weeks thereafter through 22 months or death

Outcome Measure Data

Analysis Population Description

ITT population. DR was calculated for the subgroup of participants with objective response. 27 participants in the sunitinib arm and 40 participants in the capecitabine arm reported CR or PR response and were analyzed for DR.

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	27	40
Median (95% Confidence Interval) [Months]	6.9	9.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Capecitabine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.788
	Confidence Interval	(2-Sided) 95%; 1.042 to 7.459
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Time to Tumor Response (TTR)
Description	Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target lesions. PR was defined as a >= 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.
Time Frame	From time of randomization to every 6 weeks thereafter through 22 months

Outcome Measure Data

Analysis Population Description

The study was stopped early for futility and TTR analysis was not performed.

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	0	0

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Average time from randomization to first documentation of death due to any cause.
Time Frame	From time of randomization until death

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	238	244
Median (95% Confidence Interval) [Months]	15.3	16.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Capecitabine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.219
	Comments	2-sided log-rank test with the same set of stratification factors that were used in the randomization except study sites.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.202
	Confidence Interval	(2-Sided) 95%; 0.896 to 1.611
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
Description	EORTC QLQ-C30 scales: functional (physical/role/cognitive/emotional/social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms.
Time Frame	From Day 1 of Cycle 1, then odd numbered cycles thereafter

Outcome Measure Data

Analysis Population Description

The study was stopped early for futility and EORTC QLQ-C30 analysis was not performed.

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	0	0

8. Secondary Outcome

Title	EORTC QLQ Breast Cancer Module (BR23)
Description	BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score implied a greater degree of symptoms.
Time Frame	From Day 1 of Cycle 1, then odd numbered cycles thereafter

Outcome Measure Data

Analysis Population Description

The study was stopped early for futility and EORTC QLQ Cancer Module (BR23) analysis was not performed.

Arm/Group Title	Sunitinib	Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing	1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sunitinib		Capecitabine
Arm/Group Description	37.5 mg daily, continuous dosing		1250 milligrams per square meter (mg/m^2) or 1000 mg/m^2 in older participants, twice daily for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
All Cause Mortality
	Sunitinib		Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sunitinib		Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/238 (30.3%)		44/240 (18.3%)
Blood and lymphatic system disorders
Anaemia	2/238 (0.8%)		1/240 (0.4%)
Febrile neutropenia	2/238 (0.8%)		2/240 (0.8%)
Thrombocytopenia	5/238 (2.1%)		1/240 (0.4%)
Haematotoxicity	0/238 (0%)		1/240 (0.4%)
Leukopenia	0/238 (0%)		1/240 (0.4%)
Cardiac disorders
Cardiac failure	3/238 (1.3%)		0/240 (0%)
Cardiac failure congestive	2/238 (0.8%)		0/240 (0%)
Angina pectoris	0/238 (0%)		1/240 (0.4%)
Eye disorders
Diplopia	1/238 (0.4%)		0/240 (0%)
Gastrointestinal disorders
Abdominal pain	2/238 (0.8%)		1/240 (0.4%)
Ascites	3/238 (1.3%)		0/240 (0%)
Constipation	1/238 (0.4%)		0/240 (0%)
Diarrhoea	3/238 (1.3%)		7/240 (2.9%)
Dysphagia	1/238 (0.4%)		0/240 (0%)
Gastric haemorrhage	2/238 (0.8%)		0/240 (0%)
Gastric ulcer	1/238 (0.4%)		0/240 (0%)
Gastrointestinal haemorrhage	3/238 (1.3%)		0/240 (0%)
Ileus	1/238 (0.4%)		0/240 (0%)
Mallory-Weiss syndrome	1/238 (0.4%)		0/240 (0%)
Melaena	1/238 (0.4%)		0/240 (0%)
Nausea	1/238 (0.4%)		1/240 (0.4%)
Pancreatitis acute	1/238 (0.4%)		0/240 (0%)
Peritonitis	1/238 (0.4%)		0/240 (0%)
Upper gastrointestinal haemorrhage	1/238 (0.4%)		1/240 (0.4%)
Vomiting	3/238 (1.3%)		2/240 (0.8%)
Abdominal pain upper	0/238 (0%)		1/240 (0.4%)
Diarrhoea haemorrhagic	0/238 (0%)		1/240 (0.4%)
Gastrointestinal perforation	0/238 (0%)		1/240 (0.4%)
Rectal haemorrhage	0/238 (0%)		1/240 (0.4%)
General disorders
Disease progression	14/238 (5.9%)		8/240 (3.3%)
Fatigue	3/238 (1.3%)		0/240 (0%)
General physical health deterioration	1/238 (0.4%)		0/240 (0%)
Mucosal inflammation	1/238 (0.4%)		1/240 (0.4%)
Pain	1/238 (0.4%)		0/240 (0%)
Death	0/238 (0%)		1/240 (0.4%)
Local swelling	0/238 (0%)		1/240 (0.4%)
Medical device complication	1/238 (0.4%)		0/240 (0%)
Pyrexia	0/238 (0%)		3/240 (1.3%)
Hepatobiliary disorders
Cholecystitis	1/238 (0.4%)		0/240 (0%)
Cholecystitis acute	2/238 (0.8%)		0/240 (0%)
Hepatic failure	1/238 (0.4%)		0/240 (0%)
Hepatic function abnormal	2/238 (0.8%)		0/240 (0%)
Infections and infestations
Appendicitis	1/238 (0.4%)		0/240 (0%)
Bacteraemia	1/238 (0.4%)		0/240 (0%)
Cellulitis	1/238 (0.4%)		1/240 (0.4%)
Dengue fever	1/238 (0.4%)		0/240 (0%)
Enterocolitis infectious	1/238 (0.4%)		0/240 (0%)
Erysipelas	1/238 (0.4%)		0/240 (0%)
Oesophageal candidiasis	1/238 (0.4%)		0/240 (0%)
Pneumonia	5/238 (2.1%)		0/240 (0%)
Sepsis	2/238 (0.8%)		2/240 (0.8%)
Sinusitis	1/238 (0.4%)		0/240 (0%)
Skin infection	1/238 (0.4%)		1/240 (0.4%)
Tooth infection	1/238 (0.4%)		0/240 (0%)
Urinary tract infection	1/238 (0.4%)		0/240 (0%)
Wound infection	1/238 (0.4%)		0/240 (0%)
Anal abscess	1/238 (0.4%)		0/240 (0%)
Fungal peritonitis	0/238 (0%)		1/240 (0.4%)
Peritonitis bacterial	0/238 (0%)		1/240 (0.4%)
Septic shock	0/238 (0%)		1/240 (0.4%)
Injury, poisoning and procedural complications
Fall	0/238 (0%)		1/240 (0.4%)
Postoperative respiratory distress	1/238 (0.4%)		0/240 (0%)
Hip fracture	0/238 (0%)		1/240 (0.4%)
Patella fracture	0/238 (0%)		1/240 (0.4%)
Subdural haematoma	0/238 (0%)		1/240 (0.4%)
Investigations
Blood bilirubin increased	1/238 (0.4%)		0/240 (0%)
C-reactive protein increased	1/238 (0.4%)		0/240 (0%)
Haemoglobin decreased	1/238 (0.4%)		0/240 (0%)
Liver function test abnormal	1/238 (0.4%)		0/240 (0%)
Platelet count decreased	2/238 (0.8%)		0/240 (0%)
Metabolism and nutrition disorders
Dehydration	1/238 (0.4%)		2/240 (0.8%)
Hypoglycaemia	1/238 (0.4%)		0/240 (0%)
Hypokalaemia	2/238 (0.8%)		0/240 (0%)
Hyponatraemia	1/238 (0.4%)		0/240 (0%)
Cachexia	0/238 (0%)		1/240 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/238 (0.4%)		0/240 (0%)
Bone pain	1/238 (0.4%)		0/240 (0%)
Muscular weakness	1/238 (0.4%)		0/240 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	2/238 (0.8%)		1/240 (0.4%)
Nervous system disorders
Cerebral haemorrhage	1/238 (0.4%)		0/240 (0%)
Depressed level of consciousness	1/238 (0.4%)		0/240 (0%)
Dizziness	0/238 (0%)		1/240 (0.4%)
Headache	3/238 (1.3%)		0/240 (0%)
Aphasia	1/238 (0.4%)		0/240 (0%)
Spinal cord compression	0/238 (0%)		1/240 (0.4%)
Psychiatric disorders
Confusional state	1/238 (0.4%)		0/240 (0%)
Delirium	1/238 (0.4%)		0/240 (0%)
Renal and urinary disorders
Hydronephrosis	1/238 (0.4%)		0/240 (0%)
Proteinuria	1/238 (0.4%)		0/240 (0%)
Urethral stenosis	1/238 (0.4%)		0/240 (0%)
Urinary retention	1/238 (0.4%)		0/240 (0%)
Reproductive system and breast disorders
Ovarian disorder	0/238 (0%)		1/240 (0.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/238 (1.3%)		5/240 (2.1%)
Epistaxis	3/238 (1.3%)		0/240 (0%)
Pleural effusion	3/238 (1.3%)		5/240 (2.1%)
Pneumothorax	1/238 (0.4%)		0/240 (0%)
Pulmonary embolism	1/238 (0.4%)		3/240 (1.3%)
Respiratory failure	1/238 (0.4%)		0/240 (0%)
Asphyxia	0/238 (0%)		1/240 (0.4%)
Respiratory arrest	0/238 (0%)		1/240 (0.4%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/238 (0.4%)		0/240 (0%)
Vascular disorders
Deep vein thrombosis	1/238 (0.4%)		1/240 (0.4%)
Haematoma	1/238 (0.4%)		0/240 (0%)
Hypertension	2/238 (0.8%)		0/240 (0%)
Hypotension	0/238 (0%)		1/240 (0.4%)
Other (Not Including Serious) Adverse Events
	Sunitinib		Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	228/238 (95.8%)		229/240 (95.4%)
Blood and lymphatic system disorders
Anaemia	23/238 (9.7%)		22/240 (9.2%)
Anisocytosis	0/238 (0%)		1/240 (0.4%)
Coagulopathy	0/238 (0%)		2/240 (0.8%)
Febrile neutropenia	0/238 (0%)		1/240 (0.4%)
Leukopenia	19/238 (8%)		13/240 (5.4%)
Lymphadenitis	1/238 (0.4%)		0/240 (0%)
Lymphadenopathy	1/238 (0.4%)		3/240 (1.3%)
Lymphopenia	5/238 (2.1%)		4/240 (1.7%)
Neutropenia	43/238 (18.1%)		28/240 (11.7%)
Pancytopenia	1/238 (0.4%)		0/240 (0%)
Thrombocytopenia	38/238 (16%)		5/240 (2.1%)
Cardiac disorders
Angina pectoris	1/238 (0.4%)		2/240 (0.8%)
Arrhythmia	0/238 (0%)		2/240 (0.8%)
Atrioventricular block first degree	1/238 (0.4%)		0/240 (0%)
Bradycardia	1/238 (0.4%)		0/240 (0%)
Cardiac failure	1/238 (0.4%)		0/240 (0%)
Intracardiac thrombus	1/238 (0.4%)		0/240 (0%)
Left ventricular dysfunction	2/238 (0.8%)		2/240 (0.8%)
Myocardial infarction	1/238 (0.4%)		0/240 (0%)
Palpitations	3/238 (1.3%)		2/240 (0.8%)
Pericardial effusion	2/238 (0.8%)		1/240 (0.4%)
Tachycardia	1/238 (0.4%)		3/240 (1.3%)
Ear and labyrinth disorders
Ear discomfort	1/238 (0.4%)		0/240 (0%)
Ear haemorrhage	1/238 (0.4%)		0/240 (0%)
Ear pain	0/238 (0%)		1/240 (0.4%)
Tinnitus	1/238 (0.4%)		2/240 (0.8%)
Vertigo	6/238 (2.5%)		4/240 (1.7%)
Endocrine disorders
Hyperthyroidism	4/238 (1.7%)		0/240 (0%)
Hypothyroidism	31/238 (13%)		2/240 (0.8%)
Thyroiditis chronic	0/238 (0%)		1/240 (0.4%)
Eye disorders
Blepharitis	0/238 (0%)		1/240 (0.4%)
Cataract	1/238 (0.4%)		0/240 (0%)
Conjunctivitis	7/238 (2.9%)		8/240 (3.3%)
Diplopia	1/238 (0.4%)		1/240 (0.4%)
Dry eye	3/238 (1.3%)		3/240 (1.3%)
Eye discharge	2/238 (0.8%)		1/240 (0.4%)
Eye haemorrhage	1/238 (0.4%)		0/240 (0%)
Eye irritation	1/238 (0.4%)		2/240 (0.8%)
Eye pain	0/238 (0%)		1/240 (0.4%)
Eye pruritus	0/238 (0%)		1/240 (0.4%)
Eye swelling	1/238 (0.4%)		0/240 (0%)
Eyelid oedema	8/238 (3.4%)		1/240 (0.4%)
Eyelid ptosis	0/238 (0%)		2/240 (0.8%)
Lacrimation increased	7/238 (2.9%)		9/240 (3.8%)
Ocular surface disease	1/238 (0.4%)		0/240 (0%)
Periorbital oedema	2/238 (0.8%)		0/240 (0%)
Pupils unequal	0/238 (0%)		1/240 (0.4%)
Scleral pigmentation	1/238 (0.4%)		0/240 (0%)
Scotoma	1/238 (0.4%)		0/240 (0%)
Vision blurred	3/238 (1.3%)		1/240 (0.4%)
Visual impairment	2/238 (0.8%)		0/240 (0%)
Xerophthalmia	0/238 (0%)		1/240 (0.4%)
Gastrointestinal disorders
Abdominal discomfort	4/238 (1.7%)		1/240 (0.4%)
Abdominal distension	13/238 (5.5%)		6/240 (2.5%)
Abdominal pain	21/238 (8.8%)		26/240 (10.8%)
Abdominal pain lower	3/238 (1.3%)		1/240 (0.4%)
Abdominal pain upper	29/238 (12.2%)		21/240 (8.8%)
Abdominal rigidity	1/238 (0.4%)		1/240 (0.4%)
Abdominal tenderness	2/238 (0.8%)		1/240 (0.4%)
Anal inflammation	1/238 (0.4%)		0/240 (0%)
Anorectal discomfort	0/238 (0%)		1/240 (0.4%)
Aphthous stomatitis	3/238 (1.3%)		3/240 (1.3%)
Ascites	5/238 (2.1%)		2/240 (0.8%)
Cheilitis	8/238 (3.4%)		2/240 (0.8%)
Constipation	38/238 (16%)		23/240 (9.6%)
Dental caries	1/238 (0.4%)		1/240 (0.4%)
Diarrhoea	97/238 (40.8%)		95/240 (39.6%)
Dry mouth	18/238 (7.6%)		10/240 (4.2%)
Duodenitis	1/238 (0.4%)		1/240 (0.4%)
Duodenogastric reflux	0/238 (0%)		1/240 (0.4%)
Dyspepsia	34/238 (14.3%)		13/240 (5.4%)
Dysphagia	6/238 (2.5%)		5/240 (2.1%)
Epigastric discomfort	4/238 (1.7%)		2/240 (0.8%)
Eructation	2/238 (0.8%)		1/240 (0.4%)
Flatulence	5/238 (2.1%)		5/240 (2.1%)
Food poisoning	0/238 (0%)		1/240 (0.4%)
Gastric haemorrhage	0/238 (0%)		1/240 (0.4%)
Gastritis	12/238 (5%)		4/240 (1.7%)
Gastrointestinal haemorrhage	2/238 (0.8%)		0/240 (0%)
Gastrointestinal motility disorder	1/238 (0.4%)		0/240 (0%)
Gastrointestinal pain	1/238 (0.4%)		0/240 (0%)
Gastrooesophageal reflux disease	5/238 (2.1%)		2/240 (0.8%)
Gingival bleeding	15/238 (6.3%)		1/240 (0.4%)
Gingival disorder	1/238 (0.4%)		0/240 (0%)
Gingival hypertrophy	1/238 (0.4%)		0/240 (0%)
Gingival pain	8/238 (3.4%)		0/240 (0%)
Gingival swelling	3/238 (1.3%)		1/240 (0.4%)
Gingivitis	6/238 (2.5%)		4/240 (1.7%)
Glossitis	2/238 (0.8%)		0/240 (0%)
Glossodynia	5/238 (2.1%)		1/240 (0.4%)
Haematemesis	2/238 (0.8%)		0/240 (0%)
Haemorrhoidal haemorrhage	1/238 (0.4%)		0/240 (0%)
Haemorrhoids	5/238 (2.1%)		4/240 (1.7%)
Hiatus hernia	1/238 (0.4%)		0/240 (0%)
Hypoaesthesia oral	1/238 (0.4%)		0/240 (0%)
Ileus	1/238 (0.4%)		0/240 (0%)
Irritable bowel syndrome	0/238 (0%)		1/240 (0.4%)
Lip discolouration	1/238 (0.4%)		0/240 (0%)
Lip disorder	0/238 (0%)		1/240 (0.4%)
Mouth haemorrhage	4/238 (1.7%)		0/240 (0%)
Mouth ulceration	7/238 (2.9%)		3/240 (1.3%)
Nausea	94/238 (39.5%)		75/240 (31.3%)
Odynophagia	2/238 (0.8%)		1/240 (0.4%)
Oesophageal pain	1/238 (0.4%)		1/240 (0.4%)
Oesophageal spasm	0/238 (0%)		1/240 (0.4%)
Oesophagitis	3/238 (1.3%)		3/240 (1.3%)
Oral discomfort	1/238 (0.4%)		0/240 (0%)
Oral pain	5/238 (2.1%)		1/240 (0.4%)
Painful defaecation	2/238 (0.8%)		0/240 (0%)
Periodontal disease	1/238 (0.4%)		0/240 (0%)
Periodontitis	3/238 (1.3%)		0/240 (0%)
Pneumoperitoneum	1/238 (0.4%)		0/240 (0%)
Proctalgia	1/238 (0.4%)		1/240 (0.4%)
Rectal haemorrhage	1/238 (0.4%)		2/240 (0.8%)
Reflux oesophagitis	1/238 (0.4%)		1/240 (0.4%)
Salivary hypersecretion	2/238 (0.8%)		0/240 (0%)
Stomatitis	39/238 (16.4%)		22/240 (9.2%)
Tongue ulceration	1/238 (0.4%)		1/240 (0.4%)
Tooth discolouration	1/238 (0.4%)		0/240 (0%)
Toothache	3/238 (1.3%)		3/240 (1.3%)
Vomiting	88/238 (37%)		34/240 (14.2%)
General disorders
Administration site pain	0/238 (0%)		1/240 (0.4%)
Asthenia	49/238 (20.6%)		39/240 (16.3%)
Axillary pain	3/238 (1.3%)		2/240 (0.8%)
Chest discomfort	1/238 (0.4%)		3/240 (1.3%)
Chest pain	9/238 (3.8%)		16/240 (6.7%)
Chills	4/238 (1.7%)		2/240 (0.8%)
Disease progression	1/238 (0.4%)		0/240 (0%)
Extravasation	0/238 (0%)		1/240 (0.4%)
Face oedema	17/238 (7.1%)		0/240 (0%)
Fatigue	82/238 (34.5%)		61/240 (25.4%)
Feeling hot	2/238 (0.8%)		0/240 (0%)
Gait disturbance	1/238 (0.4%)		0/240 (0%)
General physical health deterioration	3/238 (1.3%)		4/240 (1.7%)
Generalised oedema	4/238 (1.7%)		0/240 (0%)
Hyperthermia	1/238 (0.4%)		0/240 (0%)
Hypothermia	1/238 (0.4%)		0/240 (0%)
Impaired healing	2/238 (0.8%)		0/240 (0%)
Local swelling	0/238 (0%)		1/240 (0.4%)
Localised oedema	2/238 (0.8%)		0/240 (0%)
Malaise	7/238 (2.9%)		4/240 (1.7%)
Mucosal dryness	1/238 (0.4%)		0/240 (0%)
Mucosal inflammation	59/238 (24.8%)		36/240 (15%)
Nodule	0/238 (0%)		1/240 (0.4%)
Oedema	10/238 (4.2%)		2/240 (0.8%)
Oedema peripheral	19/238 (8%)		21/240 (8.8%)
Pain	6/238 (2.5%)		8/240 (3.3%)
Pyrexia	24/238 (10.1%)		23/240 (9.6%)
Sensation of foreign body	0/238 (0%)		1/240 (0.4%)
Xerosis	0/238 (0%)		1/240 (0.4%)
Hepatobiliary disorders
Biliary colic	1/238 (0.4%)		0/240 (0%)
Cholecystitis chronic	1/238 (0.4%)		0/240 (0%)
Hepatic function abnormal	2/238 (0.8%)		0/240 (0%)
Hepatic pain	0/238 (0%)		1/240 (0.4%)
Hepatic steatosis	1/238 (0.4%)		0/240 (0%)
Hepatomegaly	1/238 (0.4%)		2/240 (0.8%)
Hyperbilirubinaemia	0/238 (0%)		5/240 (2.1%)
Jaundice	2/238 (0.8%)		1/240 (0.4%)
Liver disorder	1/238 (0.4%)		1/240 (0.4%)
Immune system disorders
Drug hypersensitivity	1/238 (0.4%)		0/240 (0%)
Hypersensitivity	3/238 (1.3%)		0/240 (0%)
Iodine allergy	0/238 (0%)		1/240 (0.4%)
Infections and infestations
Amoebiasis	1/238 (0.4%)		0/240 (0%)
Bacterial infection	1/238 (0.4%)		0/240 (0%)
Breast abscess	0/238 (0%)		1/240 (0.4%)
Breast infection	0/238 (0%)		1/240 (0.4%)
Bronchitis	1/238 (0.4%)		2/240 (0.8%)
Candidiasis	1/238 (0.4%)		1/240 (0.4%)
Cellulitis	1/238 (0.4%)		3/240 (1.3%)
Cystitis	2/238 (0.8%)		2/240 (0.8%)
Dacryocystitis	1/238 (0.4%)		0/240 (0%)
Device related infection	0/238 (0%)		1/240 (0.4%)
Ear infection	0/238 (0%)		1/240 (0.4%)
Erysipelas	0/238 (0%)		1/240 (0.4%)
Eye infection	1/238 (0.4%)		1/240 (0.4%)
Folliculitis	1/238 (0.4%)		0/240 (0%)
Fungal infection	1/238 (0.4%)		1/240 (0.4%)
Gastroenteritis	3/238 (1.3%)		3/240 (1.3%)
Herpes zoster	2/238 (0.8%)		1/240 (0.4%)
Hordeolum	0/238 (0%)		1/240 (0.4%)
Infection	2/238 (0.8%)		1/240 (0.4%)
Influenza	3/238 (1.3%)		7/240 (2.9%)
Localised infection	1/238 (0.4%)		1/240 (0.4%)
Lower respiratory tract infection	0/238 (0%)		2/240 (0.8%)
Nail infection	0/238 (0%)		3/240 (1.3%)
Nasopharyngitis	15/238 (6.3%)		15/240 (6.3%)
Oesophageal candidiasis	1/238 (0.4%)		0/240 (0%)
Oral candidiasis	1/238 (0.4%)		3/240 (1.3%)
Oral herpes	2/238 (0.8%)		1/240 (0.4%)
Otitis externa	0/238 (0%)		1/240 (0.4%)
Paronychia	1/238 (0.4%)		4/240 (1.7%)
Pharyngitis	4/238 (1.7%)		4/240 (1.7%)
Pneumonia	4/238 (1.7%)		0/240 (0%)
Respiratory tract infection	2/238 (0.8%)		1/240 (0.4%)
Rhinitis	1/238 (0.4%)		1/240 (0.4%)
Skin infection	0/238 (0%)		1/240 (0.4%)
Subcutaneous abscess	0/238 (0%)		1/240 (0.4%)
Tonsillitis	0/238 (0%)		2/240 (0.8%)
Tooth abscess	1/238 (0.4%)		0/240 (0%)
Tooth infection	1/238 (0.4%)		1/240 (0.4%)
Upper respiratory tract infection	7/238 (2.9%)		8/240 (3.3%)
Urinary tract infection	12/238 (5%)		4/240 (1.7%)
Vaginal infection	2/238 (0.8%)		1/240 (0.4%)
Viral infection	1/238 (0.4%)		1/240 (0.4%)
Vulvovaginal candidiasis	0/238 (0%)		1/240 (0.4%)
Vulvovaginitis	1/238 (0.4%)		0/240 (0%)
Injury, poisoning and procedural complications
Accident	1/238 (0.4%)		0/240 (0%)
Contusion	1/238 (0.4%)		2/240 (0.8%)
Fall	1/238 (0.4%)		3/240 (1.3%)
Foot fracture	0/238 (0%)		1/240 (0.4%)
Ligament injury	0/238 (0%)		1/240 (0.4%)
Nail injury	0/238 (0%)		1/240 (0.4%)
Open wound	0/238 (0%)		1/240 (0.4%)
Radius fracture	0/238 (0%)		1/240 (0.4%)
Spinal compression fracture	1/238 (0.4%)		0/240 (0%)
Subdural haematoma	1/238 (0.4%)		0/240 (0%)
Thermal burn	1/238 (0.4%)		0/240 (0%)
Thoracic vertebral fracture	1/238 (0.4%)		0/240 (0%)
Wound	1/238 (0.4%)		1/240 (0.4%)
Wound complication	0/238 (0%)		1/240 (0.4%)
Wound secretion	0/238 (0%)		1/240 (0.4%)
Investigations
Alanine aminotransferase	2/238 (0.8%)		0/240 (0%)
Alanine aminotransferase increased	14/238 (5.9%)		5/240 (2.1%)
Aspartate aminotransferase	2/238 (0.8%)		0/240 (0%)
Aspartate aminotransferase increased	15/238 (6.3%)		6/240 (2.5%)
Blood albumin decreased	3/238 (1.3%)		0/240 (0%)
Blood alkaline phosphatase increased	4/238 (1.7%)		3/240 (1.3%)
Blood bilirubin increased	2/238 (0.8%)		6/240 (2.5%)
Blood cholesterol decreased	0/238 (0%)		1/240 (0.4%)
Blood cholesterol increased	2/238 (0.8%)		1/240 (0.4%)
Blood creatinine increased	1/238 (0.4%)		0/240 (0%)
Blood glucose increased	2/238 (0.8%)		1/240 (0.4%)
Blood lactate dehydrogenase increased	2/238 (0.8%)		0/240 (0%)
Blood phosphorus decreased	1/238 (0.4%)		0/240 (0%)
Blood potassium decreased	3/238 (1.3%)		0/240 (0%)
Blood potassium increased	1/238 (0.4%)		0/240 (0%)
Blood pressure increased	2/238 (0.8%)		0/240 (0%)
Blood thyroid stimulating hormone decreased	3/238 (1.3%)		0/240 (0%)
Blood thyroid stimulating hormone increased	12/238 (5%)		0/240 (0%)
Blood urea increased	2/238 (0.8%)		0/240 (0%)
Blood uric acid increased	2/238 (0.8%)		0/240 (0%)
Breath sounds abnormal	1/238 (0.4%)		0/240 (0%)
Electrocardiogram QT prolonged	6/238 (2.5%)		0/240 (0%)
Gamma-glutamyltransferase increased	2/238 (0.8%)		1/240 (0.4%)
Haemoglobin	1/238 (0.4%)		0/240 (0%)
Haemoglobin decreased	5/238 (2.1%)		7/240 (2.9%)
Heart rate increased	1/238 (0.4%)		0/240 (0%)
Heart sounds abnormal	1/238 (0.4%)		0/240 (0%)
International normalised ratio increased	1/238 (0.4%)		0/240 (0%)
Leucine aminopeptidase increased	1/238 (0.4%)		0/240 (0%)
Liver function test abnormal	1/238 (0.4%)		0/240 (0%)
Lymphocyte count decreased	5/238 (2.1%)		2/240 (0.8%)
Neutrophil count decreased	16/238 (6.7%)		6/240 (2.5%)
Platelet count decreased	27/238 (11.3%)		3/240 (1.3%)
Protein total decreased	1/238 (0.4%)		0/240 (0%)
Prothrombin time shortened	1/238 (0.4%)		0/240 (0%)
Pulmonary physical examination abnormal	0/238 (0%)		1/240 (0.4%)
Thyroxine increased	2/238 (0.8%)		1/240 (0.4%)
Transaminases increased	2/238 (0.8%)		0/240 (0%)
Tri-iodothyronine free increased	1/238 (0.4%)		0/240 (0%)
Weight decreased	10/238 (4.2%)		10/240 (4.2%)
Weight increased	2/238 (0.8%)		3/240 (1.3%)
White blood cell count	1/238 (0.4%)		1/240 (0.4%)
White blood cell count decreased	15/238 (6.3%)		12/240 (5%)
Metabolism and nutrition disorders
Decreased appetite	67/238 (28.2%)		48/240 (20%)
Dehydration	2/238 (0.8%)		4/240 (1.7%)
Diabetes mellitus inadequate control	0/238 (0%)		1/240 (0.4%)
Dyslipidaemia	2/238 (0.8%)		0/240 (0%)
Fluid retention	1/238 (0.4%)		0/240 (0%)
Gout	0/238 (0%)		1/240 (0.4%)
Hypercholesterolaemia	0/238 (0%)		1/240 (0.4%)
Hyperglycaemia	1/238 (0.4%)		2/240 (0.8%)
Hyperkalaemia	0/238 (0%)		1/240 (0.4%)
Hypernatraemia	0/238 (0%)		1/240 (0.4%)
Hyperuricaemia	3/238 (1.3%)		1/240 (0.4%)
Hypoalbuminaemia	3/238 (1.3%)		0/240 (0%)
Hypocalcaemia	3/238 (1.3%)		1/240 (0.4%)
Hypoglycaemia	2/238 (0.8%)		0/240 (0%)
Hypokalaemia	8/238 (3.4%)		9/240 (3.8%)
Hypomagnesaemia	0/238 (0%)		1/240 (0.4%)
Hyponatraemia	2/238 (0.8%)		1/240 (0.4%)
Hypophagia	1/238 (0.4%)		0/240 (0%)
Hypophosphataemia	3/238 (1.3%)		0/240 (0%)
Lactose intolerance	1/238 (0.4%)		0/240 (0%)
Malnutrition	0/238 (0%)		1/240 (0.4%)
Polydipsia	1/238 (0.4%)		0/240 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/238 (8%)		16/240 (6.7%)
Back pain	23/238 (9.7%)		18/240 (7.5%)
Bone fistula	1/238 (0.4%)		0/240 (0%)
Bone pain	12/238 (5%)		8/240 (3.3%)
Bursitis	1/238 (0.4%)		0/240 (0%)
Flank pain	6/238 (2.5%)		4/240 (1.7%)
Groin pain	4/238 (1.7%)		2/240 (0.8%)
Intervertebral disc protrusion	0/238 (0%)		1/240 (0.4%)
Joint range of motion decreased	0/238 (0%)		1/240 (0.4%)
Limb discomfort	0/238 (0%)		1/240 (0.4%)
Muscle spasms	4/238 (1.7%)		4/240 (1.7%)
Muscle twitching	0/238 (0%)		1/240 (0.4%)
Muscular weakness	4/238 (1.7%)		1/240 (0.4%)
Musculoskeletal chest pain	8/238 (3.4%)		7/240 (2.9%)
Musculoskeletal pain	4/238 (1.7%)		10/240 (4.2%)
Musculoskeletal stiffness	4/238 (1.7%)		0/240 (0%)
Myalgia	16/238 (6.7%)		9/240 (3.8%)
Neck pain	9/238 (3.8%)		7/240 (2.9%)
Osteoarthritis	1/238 (0.4%)		0/240 (0%)
Osteonecrosis of jaw	0/238 (0%)		1/240 (0.4%)
Pain in extremity	23/238 (9.7%)		21/240 (8.8%)
Pain in jaw	2/238 (0.8%)		0/240 (0%)
Sensation of heaviness	1/238 (0.4%)		0/240 (0%)
Synovial cyst	0/238 (0%)		1/240 (0.4%)
Tendon pain	1/238 (0.4%)		0/240 (0%)
Torticollis	1/238 (0.4%)		0/240 (0%)
Trismus	2/238 (0.8%)		0/240 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	2/238 (0.8%)		0/240 (0%)
Haemangioma	1/238 (0.4%)		0/240 (0%)
Meningioma	0/238 (0%)		1/240 (0.4%)
Tumour haemorrhage	2/238 (0.8%)		0/240 (0%)
Tumour pain	3/238 (1.3%)		4/240 (1.7%)
Nervous system disorders
Ageusia	6/238 (2.5%)		0/240 (0%)
Ataxia	0/238 (0%)		1/240 (0.4%)
Balance disorder	0/238 (0%)		1/240 (0.4%)
Carotid arteriosclerosis	1/238 (0.4%)		0/240 (0%)
Cerebellar syndrome	0/238 (0%)		1/240 (0.4%)
Convulsion	1/238 (0.4%)		3/240 (1.3%)
Dizziness	10/238 (4.2%)		15/240 (6.3%)
Dizziness postural	0/238 (0%)		1/240 (0.4%)
Dysaesthesia	1/238 (0.4%)		3/240 (1.3%)
Dysgeusia	61/238 (25.6%)		11/240 (4.6%)
Headache	38/238 (16%)		23/240 (9.6%)
Hyperaesthesia	1/238 (0.4%)		1/240 (0.4%)
Hyperreflexia	1/238 (0.4%)		0/240 (0%)
Hypersomnia	1/238 (0.4%)		0/240 (0%)
Hypoaesthesia	8/238 (3.4%)		10/240 (4.2%)
Lethargy	4/238 (1.7%)		1/240 (0.4%)
Memory impairment	0/238 (0%)		1/240 (0.4%)
Migraine	1/238 (0.4%)		0/240 (0%)
Monoparesis	0/238 (0%)		1/240 (0.4%)
Neuralgia	2/238 (0.8%)		2/240 (0.8%)
Neuropathy peripheral	3/238 (1.3%)		5/240 (2.1%)
Nystagmus	0/238 (0%)		1/240 (0.4%)
Paraesthesia	3/238 (1.3%)		10/240 (4.2%)
Peripheral motor neuropathy	0/238 (0%)		1/240 (0.4%)
Peripheral sensory neuropathy	6/238 (2.5%)		3/240 (1.3%)
Polyneuropathy	2/238 (0.8%)		3/240 (1.3%)
Sciatica	3/238 (1.3%)		0/240 (0%)
Sensory disturbance	1/238 (0.4%)		0/240 (0%)
Somnolence	2/238 (0.8%)		2/240 (0.8%)
Syncope	2/238 (0.8%)		1/240 (0.4%)
Transient ischaemic attack	1/238 (0.4%)		0/240 (0%)
Tremor	1/238 (0.4%)		1/240 (0.4%)
VIIth nerve paralysis	1/238 (0.4%)		0/240 (0%)
VIth nerve disorder	0/238 (0%)		1/240 (0.4%)
Psychiatric disorders
Anxiety	7/238 (2.9%)		5/240 (2.1%)
Confusional state	1/238 (0.4%)		0/240 (0%)
Delirium	1/238 (0.4%)		0/240 (0%)
Depressed mood	0/238 (0%)		1/240 (0.4%)
Depression	5/238 (2.1%)		7/240 (2.9%)
Disorientation	0/238 (0%)		1/240 (0.4%)
Hallucination	1/238 (0.4%)		0/240 (0%)
Insomnia	21/238 (8.8%)		14/240 (5.8%)
Mood swings	0/238 (0%)		1/240 (0.4%)
Nightmare	1/238 (0.4%)		0/240 (0%)
Panic attack	0/238 (0%)		1/240 (0.4%)
Renal and urinary disorders
Chromaturia	3/238 (1.3%)		0/240 (0%)
Dysuria	2/238 (0.8%)		1/240 (0.4%)
Hydronephrosis	1/238 (0.4%)		0/240 (0%)
Perinephric effusion	1/238 (0.4%)		0/240 (0%)
Proteinuria	9/238 (3.8%)		0/240 (0%)
Renal colic	1/238 (0.4%)		0/240 (0%)
Renal failure	1/238 (0.4%)		0/240 (0%)
Renal impairment	1/238 (0.4%)		0/240 (0%)
Renal pain	1/238 (0.4%)		0/240 (0%)
Urethral disorder	1/238 (0.4%)		0/240 (0%)
Urinary incontinence	0/238 (0%)		1/240 (0.4%)
Urinary retention	1/238 (0.4%)		0/240 (0%)
Reproductive system and breast disorders
Atrophic vulvovaginitis	0/238 (0%)		1/240 (0.4%)
Breast disorder	1/238 (0.4%)		0/240 (0%)
Breast haemorrhage	0/238 (0%)		1/240 (0.4%)
Breast mass	2/238 (0.8%)		1/240 (0.4%)
Breast pain	4/238 (1.7%)		6/240 (2.5%)
Breast swelling	1/238 (0.4%)		0/240 (0%)
Dysfunctional uterine bleeding	0/238 (0%)		1/240 (0.4%)
Menstruation irregular	0/238 (0%)		1/240 (0.4%)
Metrorrhagia	0/238 (0%)		1/240 (0.4%)
Pelvic pain	0/238 (0%)		1/240 (0.4%)
Pruritus genital	1/238 (0.4%)		0/240 (0%)
Uterine haemorrhage	0/238 (0%)		1/240 (0.4%)
Vaginal prolapse	1/238 (0.4%)		0/240 (0%)
Vulvovaginal discomfort	0/238 (0%)		1/240 (0.4%)
Vulvovaginal dryness	1/238 (0.4%)		0/240 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/238 (0.4%)		0/240 (0%)
Cough	28/238 (11.8%)		18/240 (7.5%)
Dry throat	1/238 (0.4%)		0/240 (0%)
Dysphonia	11/238 (4.6%)		3/240 (1.3%)
Dyspnoea	25/238 (10.5%)		25/240 (10.4%)
Dyspnoea exertional	2/238 (0.8%)		1/240 (0.4%)
Epistaxis	20/238 (8.4%)		6/240 (2.5%)
Haemoptysis	2/238 (0.8%)		2/240 (0.8%)
Hiccups	1/238 (0.4%)		0/240 (0%)
Hyperventilation	1/238 (0.4%)		0/240 (0%)
Hypoventilation	0/238 (0%)		1/240 (0.4%)
Hypoxia	1/238 (0.4%)		0/240 (0%)
Increased upper airway secretion	0/238 (0%)		1/240 (0.4%)
Lung disorder	1/238 (0.4%)		0/240 (0%)
Nasal congestion	2/238 (0.8%)		1/240 (0.4%)
Nasal disorder	1/238 (0.4%)		0/240 (0%)
Nasal dryness	1/238 (0.4%)		1/240 (0.4%)
Nasal inflammation	2/238 (0.8%)		0/240 (0%)
Nasal obstruction	1/238 (0.4%)		1/240 (0.4%)
Oropharyngeal pain	9/238 (3.8%)		3/240 (1.3%)
Pleural effusion	9/238 (3.8%)		6/240 (2.5%)
Productive cough	2/238 (0.8%)		0/240 (0%)
Pulmonary embolism	0/238 (0%)		2/240 (0.8%)
Pulmonary haemorrhage	1/238 (0.4%)		0/240 (0%)
Pulmonary hypertension	1/238 (0.4%)		0/240 (0%)
Respiratory failure	0/238 (0%)		1/240 (0.4%)
Rhinitis allergic	1/238 (0.4%)		0/240 (0%)
Rhinorrhoea	3/238 (1.3%)		4/240 (1.7%)
Sputum increased	1/238 (0.4%)		1/240 (0.4%)
Tachypnoea	0/238 (0%)		1/240 (0.4%)
Upper-airway cough syndrome	0/238 (0%)		1/240 (0.4%)
Skin and subcutaneous tissue disorders
Acne	5/238 (2.1%)		0/240 (0%)
Actinic keratosis	0/238 (0%)		1/240 (0.4%)
Alopecia	11/238 (4.6%)		6/240 (2.5%)
Blister	1/238 (0.4%)		3/240 (1.3%)
Decubitus ulcer	1/238 (0.4%)		0/240 (0%)
Dermatitis	3/238 (1.3%)		2/240 (0.8%)
Dermatitis acneiform	3/238 (1.3%)		0/240 (0%)
Dermatitis allergic	0/238 (0%)		1/240 (0.4%)
Dermatitis bullous	1/238 (0.4%)		0/240 (0%)
Dry skin	13/238 (5.5%)		13/240 (5.4%)
Ecchymosis	4/238 (1.7%)		0/240 (0%)
Eczema	3/238 (1.3%)		2/240 (0.8%)
Erythema	7/238 (2.9%)		5/240 (2.1%)
Exfoliative rash	0/238 (0%)		1/240 (0.4%)
Haemorrhage subcutaneous	1/238 (0.4%)		0/240 (0%)
Hair colour changes	8/238 (3.4%)		0/240 (0%)
Hyperhidrosis	2/238 (0.8%)		1/240 (0.4%)
Hyperkeratosis	5/238 (2.1%)		1/240 (0.4%)
Koilonychia	0/238 (0%)		1/240 (0.4%)
Madarosis	0/238 (0%)		1/240 (0.4%)
Nail bed inflammation	0/238 (0%)		1/240 (0.4%)
Nail discolouration	1/238 (0.4%)		3/240 (1.3%)
Nail disorder	5/238 (2.1%)		2/240 (0.8%)
Nail pigmentation	3/238 (1.3%)		0/240 (0%)
Nail toxicity	0/238 (0%)		5/240 (2.1%)
Onychoclasis	2/238 (0.8%)		2/240 (0.8%)
Onycholysis	0/238 (0%)		1/240 (0.4%)
Palmar erythema	0/238 (0%)		1/240 (0.4%)
Palmar-plantar erythrodysaesthesia syndrome	80/238 (33.6%)		149/240 (62.1%)
Petechiae	5/238 (2.1%)		0/240 (0%)
Photosensitivity reaction	0/238 (0%)		1/240 (0.4%)
Pigmentation disorder	1/238 (0.4%)		9/240 (3.8%)
Pruritus	4/238 (1.7%)		5/240 (2.1%)
Purpura	1/238 (0.4%)		0/240 (0%)
Rash	28/238 (11.8%)		19/240 (7.9%)
Rash papular	1/238 (0.4%)		2/240 (0.8%)
Rash vesicular	1/238 (0.4%)		0/240 (0%)
Skin discolouration	18/238 (7.6%)		1/240 (0.4%)
Skin disorder	1/238 (0.4%)		0/240 (0%)
Skin exfoliation	2/238 (0.8%)		3/240 (1.3%)
Skin fissures	0/238 (0%)		4/240 (1.7%)
Skin hyperpigmentation	6/238 (2.5%)		23/240 (9.6%)
Skin hypopigmentation	2/238 (0.8%)		2/240 (0.8%)
Skin lesion	3/238 (1.3%)		3/240 (1.3%)
Skin mass	0/238 (0%)		1/240 (0.4%)
Skin reaction	2/238 (0.8%)		2/240 (0.8%)
Skin toxicity	1/238 (0.4%)		2/240 (0.8%)
Skin ulcer	7/238 (2.9%)		5/240 (2.1%)
Skin ulcer haemorrhage	1/238 (0.4%)		0/240 (0%)
Swelling face	4/238 (1.7%)		0/240 (0%)
Yellow skin	19/238 (8%)		0/240 (0%)
Surgical and medical procedures
Skin neoplasm excision	0/238 (0%)		1/240 (0.4%)
Tooth extraction	1/238 (0.4%)		0/240 (0%)
Vascular disorders
Circulatory collapse	0/238 (0%)		1/240 (0.4%)
Deep vein thrombosis	1/238 (0.4%)		2/240 (0.8%)
Flushing	0/238 (0%)		1/240 (0.4%)
Haematoma	5/238 (2.1%)		0/240 (0%)
Haemorrhage	1/238 (0.4%)		1/240 (0.4%)
Hot flush	4/238 (1.7%)		5/240 (2.1%)
Hypertension	53/238 (22.3%)		6/240 (2.5%)
Hypotension	1/238 (0.4%)		2/240 (0.8%)
Lymphoedema	3/238 (1.3%)		7/240 (2.9%)
Orthostatic hypotension	1/238 (0.4%)		0/240 (0%)
Pallor	1/238 (0.4%)		1/240 (0.4%)
Phlebitis	0/238 (0%)		1/240 (0.4%)
Thrombophlebitis	0/238 (0%)		1/240 (0.4%)
Thrombophlebitis superficial	0/238 (0%)		1/240 (0.4%)
Thrombosis	0/238 (0%)		1/240 (0.4%)
Venous thrombosis	1/238 (0.4%)		0/240 (0%)

Limitations/Caveats

Due to patient enrollment termination, PFS/OR/TTP/DR were done by investigator assessment due to lack of central review data and TTR/EORTC QLQ-C30/QLQ BR23 analyses were not done. Those enrolled could receive capecitabine or enter an extension trial.

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Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.