A Study Of Sunitinib Compared To Placebo For Patients With Advanced Pancreatic Islet Cell Tumors

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ClinicalTrials.gov Identifier: NCT00428597

Recruitment Status : Terminated (Refer to Detailed Description.)

First Posted : January 30, 2007

Results First Posted : October 11, 2010

Last Update Posted : October 11, 2010

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Sponsor:

Information provided by:

Pfizer

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Conditions	Carcinoma, Islet Cell Carcinoma, Pancreas
Interventions	Drug: sunitinib malate Drug: Placebo
Enrollment	171

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description	Oral sunitinib 37.5 milligrams (mg)...	Matching placebo.
Arm/Group Description	Oral sunitinib 37.5 milligrams (mg) once daily on a continuous daily dosing schedule.	Matching placebo.
Period Title: Overall Study
Started	86	85
Received Treatment	83	82
Completed	0	0
Not Completed	86	85
Reason Not Completed
Randomized but not treated	3	3
Objective Progression or Relapse	19	47
Study Terminated by Sponsor	41	16
Adverse Event	15	7
Global Deterioration of Health Status	1	5
Protocol Violation	2	1
Withdrawal by Subject	2	1
Other	1	1
Lost to Follow-up	0	1
Pregnancy	1	0
Death	1	3

Baseline Characteristics

Arm/Group Title		Sunitinib	Placebo	Total
Arm/Group Description		Oral sunitinib 37.5 mg once daily o...	Matching placebo.	Total of all reporting groups
Arm/Group Description		Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.	Total of all reporting groups
Overall Number of Baseline Participants		86	85	171
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	86 participants	85 participants	171 participants
Between 18 and 44 years		19	17	36
Between 45 and 64		45	45	90
>=65 years		22	23	45
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	86 participants	85 participants	171 participants
	Female	44 51.2%	45 52.9%	89 52.0%
	Male	42 48.8%	40 47.1%	82 48.0%

Outcome Measures

1.Primary Outcome


Title	Progression Free Survival (PFS)
Description	Time from randomization to first progression of disease (PD) or death ...
Description	Time from randomization to first progression of disease (PD) or death for any reason in the absence of documented PD. PFS was calculated as (first event date minus first randomization date +1) divided by 30.4.
Time Frame	From time of randomization through Day 1 of Week 5, Week 9, and then every 8 weeks thereafter until disease progression or death

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population = all subjects who were randomized.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	86	85
Median (95% Confidence Interval) Unit of Measure: Months
	11.4 (7.4 to 19.8)	5.5 (3.6 to 7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.000118
	Comments	Log-rank test statistic and 2-sided p-value from the unstratified log-rank test
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.418
	Confidence Interval	(2-Sided) 95% 0.263 to 0.662
	Estimation Comments	Hazard ratio based on the Cox Proportional hazards model

2.Secondary Outcome


Title	Number of Subjects With Objective Response
Description	Objective response = subjects with confirmed complete response (CR) or...
Description	Objective response = subjects with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) for at least 4 weeks, confirmed by repeat tumor assessments. A CR was defined as the disappearance of all target lesions. A PR was defined as a > = 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 through Day 1 of Week 5, 9, and every 8 weeks thereafter

Outcome Measure Data

Analysis Population Description

ITT. No placebo subjects had objective response.


Arm/Group Title	Sunitinib
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.
Overall Number of Participants Analyzed	86
Measure Type: Number Unit of Measure: participants
	8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	9.3
	Confidence Interval	(2-Sided) 95% 4.1 to 17.5
	Estimation Comments	Confidence interval (CI) using exact method based on binomial distribution.

3.Secondary Outcome


Title	Duration of Response (DR)
Description	Time in months from the first documentation of objective tumor respons...
Description	Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4.
Time Frame	From start of treatment through Day 1 of Week 5, 9, and every 8 weeks thereafter until disease progression or death due to any cause

Outcome Measure Data

Analysis Population Description

ITT. DR was calculated for the subgroup of subjects with objective response. 8 sunitinib subjects reported CR or PR response and were analyzed for DR; no placebo subjects reported CR or PR.


Arm/Group Title	Sunitinib
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.
Overall Number of Participants Analyzed	8
Median (Full Range) Unit of Measure: Months
	8.1 (1.0 to 15.0)

4.Secondary Outcome


Title	Time-to-Tumor Response (TTR)
Description	Time from randomization to the first documentation of objective tumor ...
Description	Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.
Time Frame	From time of randomization through Day 1 of Week 5, 9, and every 8 weeks thereafter

Outcome Measure Data

Analysis Population Description

ITT. TTR was calculated for the subgroup of subjects with objective response. 8 sunitinib subjects reported CR or PR response and were analyzed for TTR; no placebo subjects reported CR or PR.


Arm/Group Title	Sunitinib
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.
Overall Number of Participants Analyzed	8
Median (Full Range) Unit of Measure: Months
	3.1 (0.8 to 11.1)

5.Secondary Outcome


Title	Overall Survival (OS)
Description	Time in months from time of randomization to date of death due to any ...
Description	Time in months from time of randomization to date of death due to any cause. The median number of months is provided; however, the study was terminated early. OS data was not mature by the time of analysis. Median OS time cannot be accurately estimated by Kaplan-Meier method for either treatment arm.
Time Frame	From start of study treatment up to 22 months

Outcome Measure Data

Analysis Population Description

ITT. The median OS in months could not be calculated for placebo.


Arm/Group Title	Sunitinib
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.
Overall Number of Participants Analyzed	86
Median (95% Confidence Interval) Unit of Measure: months
	20.6 ^[1] (20.6 to NA)

[1]

The upper confidence interval was not reached.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0204
	Comments	2-sided p-value from the unstratified log-rank test.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.409
	Confidence Interval	(2-Sided) 95% 0.187 to 0.894
	Estimation Comments	Hazard ratio based on the Cox Proportional hazards model.

6.Secondary Outcome


Title	European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire (EORTC QLQ-C30) - Global Quality of Life (QoL) Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

Patient Reported Outcome (PRO) population=subjects from the ITT population who had completed at least 1 EORTC QLQ-C30 assessment while on treatment. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=66, 66)	67.0 (20.3)	64.0 (22.7)
Cycle 2 (n=68, 66)	62.1 (19.9)	62.6 (23.6)
Cycle 3 (n=60, 56)	62.6 (20.7)	63.5 (25.1)
Cycle 4 (n=55, 43)	62.0 (21.8)	61.6 (23.3)
Cycle 5 (n=48, 40)	63.5 (21.9)	61.7 (25.4)
Cycle 6 (n=42, 31)	66.9 (22.0)	56.7 (29.8)
Cycle 7 (n=37, 28)	66.2 (23.0)	64.6 (23.4)
Cycle 8 (n=33, 22)	65.9 (23.6)	62.1 (23.2)
Cycle 9 (n=33, 18)	67.2 (19.1)	64.4 (22.1)
Cycle 10 (n=29, 14)	71.0 (20.1)	59.5 (24.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6799
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.1543
	Confidence Interval	(2-Sided) 95% -4.3 to 6.6
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

7.Secondary Outcome


Title	EORTC QLQ-C30 - Cognitive Functioning Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles with less than 10 subjects are not reported due to lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	87.1 (16.6)	87.1 (18.2)
Cycle 2 (n=69, 66)	82.9 (20.0)	78.5 (24.4)
Cycle 3 (n=60, 56)	80.1 (19.9)	80.8 (22.7)
Cycle 4 (n=55, 43)	79.7 (24.2)	82.6 (18.5)
Cycle 5 (n=48, 40)	82.3 (20.2)	82.9 (21.8)
Cycle 6 (n=42, 31)	82.1 (22.5)	82.3 (20.6)
Cycle 7 (n=38, 28)	84.6 (21.0)	88.1 (15.6)
Cycle 8 (n=34, 22)	84.3 (18.3)	79.5 (23.0)
Cycle 9 (n=33, 18)	80.3 (21.8)	83.3 (18.1)
Cycle 10 (n=29, 14)	80.5 (24.0)	85.7 (19.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6058
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.4404
	Confidence Interval	(2-Sided) 95% -6.9 to 4
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

8.Secondary Outcome


Title	EORTC QLQ-C30 - Emotional Functioning Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	75.2 (23.0)	73.7 (26.2)
Cycle 2 (n=69, 66)	76.2 (22.1)	73.1 (27.1)
Cycle 3 (n=60, 56)	75.3 (20.2)	70.8 (25.8)
Cycle 4 (n=55, 43)	72.2 (23.2)	76.9 (22.3)
Cycle 5 (n=48, 40)	72.6 (25.2)	75.8 (23.9)
Cycle 6 (n=42, 31)	77.8 (23.8)	72.8 (28.9)
Cycle 7 (n=38, 28)	75.3 (28.6)	80.8 (19.8)
Cycle 8 (n=34, 22)	74.0 (30.9)	76.7 (21.6)
Cycle 9 (n=33, 18)	75.4 (23.4)	75.8 (30.0)
Cycle 10 (n=29, 14)	76.4 (23.4)	76.2 (20.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3008
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.5575
	Confidence Interval	(2-Sided) 95% -10.3 to 3.2
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

9.Secondary Outcome


Title	EORTC QLQ-C30 - Physical Functioning Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	83.1 (20.5)	83.1 (20.6)
Cycle 2 (n=69, 67)	77.7 (20.5)	77.1 (25.9)
Cycle 3 (n=60, 56)	78.2 (21.6)	75.5 (28.5)
Cycle 4 (n=55, 43)	77.5 (21.3)	78.4 (24.5)
Cycle 5 (n=48, 40)	78.3 (20.2)	80.7 (21.9)
Cycle 6 (n=42, 30)	80.9 (16.3)	81.1 (22.3)
Cycle 7 (n=38, 28)	80.3 (18.8)	78.9 (25.4)
Cycle 8 (n=34, 22)	79.4 (20.7)	73.5 (28.1)
Cycle 9 (n=33, 18)	78.8 (17.0)	79.6 (24.8)
Cycle 10 (n=29, 14)	81.4 (18.9)	78.6 (23.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3230
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7911
	Confidence Interval	(2-Sided) 95% -2.8 to 8.3
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

10.Secondary Outcome


Title	EORTC QLQ-C30 - Role Functioning Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	84.3 (23.4)	77.5 (27.7)
Cycle 2 (n=69, 67)	71.6 (28.9)	68.9 (30.6)
Cycle 3 (n=60, 56)	71.0 (26.7)	70.5 (31.0)
Cycle 4 (n=55, 43)	72.1 (28.9)	73.3 (29.6)
Cycle 5 (n=48, 41)	71.5 (27.7)	75.0 (31.4)
Cycle 6 (n=42, 31)	76.6 (26.6)	66.1 (32.6)
Cycle 7 (n=38, 28)	75.7 (28.8)	72.3 (29.7)
Cycle 8 (n=34, 22)	73.0 (29.6)	66.7 (30.9)
Cycle 9 (n=33, 18)	72.2 (24.2)	67.6 (31.6)
Cycle 10 (n=29, 14)	79.9 (22.4)	70.2 (28.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7113
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.5113
	Confidence Interval	(2-Sided) 95% -6.5 to 9.5
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

11.Secondary Outcome


Title	EORTC QLQ-C30 - Social Functioning Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	79.4 (27.2)	77.0 (31.5)
Cycle 2 (n=69, 66)	77.8 (22.1)	75.0 (31.0)
Cycle 3 (n=60, 56)	77.1 (23.1)	77.2 (28.8)
Cycle 4 (n=55, 43)	71.2 (28.4)	79.8 (26.1)
Cycle 5 (n=48, 40)	74.3 (23.8)	77.3 (30.2)
Cycle 6 (n=42, 31)	79.0 (26.3)	74.7 (31.0)
Cycle 7 (n=38, 28)	76.3 (29.2)	83.9 (25.5)
Cycle 8 (n=34, 22)	72.5 (30.4)	74.2 (31.6)
Cycle 9 (n=33, 18)	76.3 (21.7)	74.1 (33.4)
Cycle 10 (n=29, 14)	75.9 (25.8)	81.0 (24.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6487
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.6672
	Confidence Interval	(2-Sided) 95% -8.9 to 5.5
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

12.Secondary Outcome


Title	EORTC QLQ-C30 - Appetite Loss Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	16.9 (25.5)	18.7 (27.5)
Cycle 2 (n=69, 67)	25.1 (33.0)	20.4 (31.8)
Cycle 3 (n=60, 56)	25.0 (34.5)	23.8 (32.9)
Cycle 4 (n=55, 43)	33.3 (34.5)	22.5 (27.9)
Cycle 5 (n=48, 41)	26.4 (33.7)	24.0 (30.7)
Cycle 6 (n=42, 31)	20.6 (30.3)	23.7 (30.1)
Cycle 7 (n=38, 28)	24.6 (29.7)	19.0 (29.3)
Cycle 8 (n=34, 21)	24.5 (31.0)	30.2 (33.2)
Cycle 9 (n=33, 18)	23.2 (27.0)	22.2 (32.3)
Cycle 10 (n=29, 14)	18.4 (29.0)	21.4 (33.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6545
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.8800
	Confidence Interval	(2-Sided) 95% -6.4 to 10.1
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

13.Secondary Outcome


Title	EORTC QLQ-C30 - Constipation Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 65)	14.9 (24.8)	14.9 (23.6)
Cycle 2 (n=69, 66)	8.2 (16.6)	13.6 (23.4)
Cycle 3 (n=59, 56)	9.0 (20.4)	18.5 (28.4)
Cycle 4 (n=55, 43)	9.1 (17.5)	14.0 (24.4)
Cycle 5 (n=48, 41)	7.6 (17.2)	15.9 (24.7)
Cycle 6 (n=42, 31)	11.1 (15.9)	14.0 (26.9)
Cycle 7 (n=37, 28)	9.9 (19.0)	10.1 (23.7)
Cycle 8 (n=34, 22)	11.8 (18.1)	18.2 (32.1)
Cycle 9 (n=32, 18)	10.4 (15.7)	18.5 (32.8)
Cycle 10 (n=29, 14)	13.8 (18.9)	16.7 (31.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1936
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.0035
	Confidence Interval	(2-Sided) 95% -10 to 2
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

14.Secondary Outcome


Title	EORTC QLQ-C30 - Diarrhea Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	20.4 (29.6)	19.2 (28.1)
Cycle 2 (n=69, 66)	37.7 (35.2)	18.2 (27.5)
Cycle 3 (n=60, 56)	34.2 (33.7)	16.7 (26.2)
Cycle 4 (n=55, 43)	38.8 (32.6)	18.6 (27.5)
Cycle 5 (n=47, 40)	42.6 (36.6)	15.0 (25.0)
Cycle 6 (n=42, 31)	38.9 (32.9)	18.3 (28.3)
Cycle 7 (n=38, 28)	41.7 (30.0)	16.7 (29.4)
Cycle 8 (n=33, 22)	43.4 (31.7)	15.9 (26.5)
Cycle 9 (n=33, 18)	40.4 (29.8)	14.8 (20.5)
Cycle 10 (n=29, 14)	40.2 (32.6)	9.5 (15.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.3801
	Confidence Interval	(2-Sided) 95% 14.3 to 28.4
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

15.Secondary Outcome


Title	EORTC QLQ-C30 - Dyspnea Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	15.9 (21.2)	19.7 (29.2)
Cycle 2 (n=69, 66)	23.2 (26.4)	22.7 (29.3)
Cycle 3 (n=60, 56)	20.6 (24.6)	20.8 (30.2)
Cycle 4 (n=55, 43)	25.5 (26.4)	22.5 (27.9)
Cycle 5 (n=48, 41)	20.8 (27.2)	16.3 (22.5)
Cycle 6 (n=42, 30)	19.0 (23.4)	15.6 (31.2)
Cycle 7 (n=38, 28)	19.3 (24.1)	19.6 (26.1)
Cycle 8 (n=34, 22)	22.5 (28.1)	21.2 (30.1)
Cycle 9 (n=32, 18)	25.0 (25.4)	18.5 (28.5)
Cycle 10 (n=29, 14)	18.4 (26.1)	16.7 (25.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1339
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.2300
	Confidence Interval	(2-Sided) 95% -1.6 to 12.1
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

16.Secondary Outcome


Title	EORTC QLQ-C30 - Fatigue Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	29.4 (23.7)	34.5 (26.4)
Cycle 2 (n=69, 67)	44.3 (24.2)	40.1 (30.1)
Cycle 3 (n=60, 56)	41.2 (23.6)	42.3 (32.6)
Cycle 4 (n=55, 43)	41.0 (26.0)	37.0 (29.5)
Cycle 5 (n=48, 41)	34.7 (23.4)	36.3 (31.8)
Cycle 6 (n=42, 31)	34.9 (25.9)	42.3 (33.1)
Cycle 7 (n=38, 28)	36.5 (24.9)	34.9 (27.2)
Cycle 8 (n=34, 22)	39.9 (28.4)	43.2 (33.0)
Cycle 9 (n=33, 18)	37.4 (22.5)	37.7 (27.8)
Cycle 10 (n=29, 14)	33.7 (23.7)	43.7 (30.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6138
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.7816
	Confidence Interval	(2-Sided) 95% -5.1 to 8.7
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

17.Secondary Outcome


Title	EORTC QLQ-C30 - Financial Difficulties Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	19.9 (32.3)	15.7 (27.6)
Cycle 2 (n=68, 65)	14.2 (26.0)	14.4 (26.3)
Cycle 3 (n=59, 56)	15.8 (25.8)	16.7 (28.4)
Cycle 4 (n=55, 43)	18.2 (27.8)	12.4 (27.2)
Cycle 5 (n=48, 40)	18.1 (28.3)	13.3 (24.8)
Cycle 6 (n=42, 30)	19.0 (29.6)	11.1 (23.7)
Cycle 7 (n=38, 28)	20.2 (33.4)	10.7 (22.3)
Cycle 8 (n=34, 22)	18.6 (32.0)	13.6 (19.7)
Cycle 9 (n=33, 18)	20.2 (26.3)	14.8 (28.5)
Cycle 10 (n=29, 14)	17.2 (29.0)	14.3 (31.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.9367
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2778
	Confidence Interval	(2-Sided) 95% -6.6 to 7.1
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

18.Secondary Outcome


Title	EORTC QLQ-C30 - Insomnia Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	25.4 (29.6)	26.3 (27.7)
Cycle 2 (n=69, 67)	36.7 (35.8)	27.4 (30.7)
Cycle 3 (n=59, 56)	35.6 (30.9)	24.7 (27.2)
Cycle 4 (n=55, 43)	35.2 (33.0)	22.5 (24.9)
Cycle 5 (n=48, 41)	25.0 (26.2)	24.0 (27.4)
Cycle 6 (n=42, 30)	31.0 (32.4)	28.9 (35.8)
Cycle 7 (n=38, 28)	32.9 (35.6)	23.2 (29.2)
Cycle 8 (n=34, 22)	28.4 (34.9)	28.8 (23.7)
Cycle 9 (n=33, 18)	26.3 (32.0)	29.6 (30.0)
Cycle 10 (n=29, 14)	31.0 (34.4)	23.8 (24.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0372
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.7530
	Confidence Interval	(2-Sided) 95% 0.5 to 15
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

19.Secondary Outcome


Title	EORTC QLQ-C30 - Nausea and Vomiting Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	6.7 (12.3)	12.6 (22.1)
Cycle 2 (n=69, 67)	13.0 (19.6)	16.4 (21.8)
Cycle 3 (n=60, 56)	15.8 (22.6)	15.3 (25.4)
Cycle 4 (n=55, 43)	15.8 (21.4)	15.1 (24.1)
Cycle 5 (n=48, 41)	15.6 (25.1)	11.6 (15.9)
Cycle 6 (n=42, 31)	11.5 (16.7)	14.5 (17.6)
Cycle 7 (n=38, 28)	13.8 (19.6)	9.5 (16.0)
Cycle 8 (n=34, 22)	11.8 (22.3)	16.3 (25.0)
Cycle 9 (n=33, 18)	9.6 (16.7)	6.5 (11.6)
Cycle 10 (n=29, 14)	8.6 (14.5)	3.6 (9.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6939
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.1463
	Confidence Interval	(2-Sided) 95% -4.6 to 6.9
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

20.Secondary Outcome


Title	EORTC QLQ-C30 - Pain Subscale
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical,...
Description	EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 and every 4 weeks thereafter (Day 1 of each 4-week cycle) and at end of treatment/withdrawal

Outcome Measure Data

Analysis Population Description

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.


Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description:	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
Overall Number of Participants Analyzed	73	71
Mean (Standard Deviation) Unit of Measure: scores on a scale
Cycle 1 (n=67, 66)	22.9 (24.4)	22.5 (28.9)
Cycle 2 (n=69, 67)	29.5 (27.6)	28.6 (34.5)
Cycle 3 (n=60, 56)	28.1 (27.4)	28.7 (32.0)
Cycle 4 (n=55, 43)	25.5 (27.9)	24.0 (28.7)
Cycle 5 (n=48, 41)	26.7 (25.4)	28.0 (32.8)
Cycle 6 (n=42, 31)	25.0 (25.6)	31.2 (34.1)
Cycle 7 (n=38, 28)	23.9 (26.9)	23.5 (25.6)
Cycle 8 (n=34, 22)	23.0 (26.6)	28.0 (33.1)
Cycle 9 (n=33, 18)	25.3 (24.7)	22.2 (32.8)
Cycle 10 (n=29, 14)	17.2 (15.7)	26.2 (26.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Cycle 2 through Cycle 10
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3711
	Comments	From repeated measures mixed-effects with intercept term, treatment, time from first dose, treatment-by-time interaction and baseline score (intercept and time from dose as random effects). No p-value adjustments were made for multiple comparisons.
	Method	Repeated Measures Mixed-Effects Model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.5128
	Confidence Interval	(2-Sided) 95% -11.2 to 4.2
	Estimation Comments	Estimated mean difference with 95% CI and p-value were obtained from the repeated measures mixed-effects model using data from Cycle 2 through Cycle 10.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description	Oral sunitinib 37.5 mg once daily o...	Matching placebo.
Arm/Group Description	Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.	Matching placebo.
All-Cause Mortality
	Sunitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Sunitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	22/83 (26.51%)	34/82 (41.46%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Leukopenia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Neutropenia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Thrombocytopenia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Cardiac disorders
Cardiac failure ^† 1	2/83 (2.41%)	0/82 (0.00%)
Ventricular arrhythmia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Eye disorders
Eye disorder ^† 1	1/83 (1.20%)	0/82 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	2/83 (2.41%)	4/82 (4.88%)
Abdominal pain upper ^† 1	2/83 (2.41%)	0/82 (0.00%)
Ascites ^† 1	1/83 (1.20%)	0/82 (0.00%)
Diarrhoea ^† 1	1/83 (1.20%)	0/82 (0.00%)
Duodenal ulcer ^† 1	1/83 (1.20%)	1/82 (1.22%)
Duodenal ulcer perforation ^† 1	0/83 (0.00%)	1/82 (1.22%)
Erosive duodenitis ^† 1	0/83 (0.00%)	1/82 (1.22%)
Haematemesis ^† 1	0/83 (0.00%)	2/82 (2.44%)
Ileus ^† 1	0/83 (0.00%)	1/82 (1.22%)
Mallory-Weiss syndrome ^† 1	1/83 (1.20%)	0/82 (0.00%)
Melaena ^† 1	0/83 (0.00%)	2/82 (2.44%)
Nausea ^† 1	2/83 (2.41%)	1/82 (1.22%)
Pancreatitis ^† 1	1/83 (1.20%)	0/82 (0.00%)
Pancreatitis acute ^† 1	0/83 (0.00%)	1/82 (1.22%)
Rectal haemorrhage ^† 1	0/83 (0.00%)	1/82 (1.22%)
Varices oesophageal ^† 1	1/83 (1.20%)	0/82 (0.00%)
Vomiting ^† 1	2/83 (2.41%)	3/82 (3.66%)
General disorders
Asthenia ^† 1	0/83 (0.00%)	1/82 (1.22%)
Disease progression ^† 1	3/83 (3.61%)	2/82 (2.44%)
Fatigue ^† 1	1/83 (1.20%)	1/82 (1.22%)
General physical health deterioration ^† 1	1/83 (1.20%)	2/82 (2.44%)
Hyperthermia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Inflammation ^† 1	0/83 (0.00%)	1/82 (1.22%)
Mucosal inflammation ^† 1	1/83 (1.20%)	0/82 (0.00%)
Multi-organ failure ^† 1	0/83 (0.00%)	1/82 (1.22%)
Oedema ^† 1	0/83 (0.00%)	1/82 (1.22%)
Oedema peripheral ^† 1	0/83 (0.00%)	1/82 (1.22%)
Pyrexia ^† 1	1/83 (1.20%)	2/82 (2.44%)
Hepatobiliary disorders
Bile duct obstruction ^† 1	1/83 (1.20%)	0/82 (0.00%)
Cholangitis ^† 1	0/83 (0.00%)	1/82 (1.22%)
Hepatic failure ^† 1	0/83 (0.00%)	2/82 (2.44%)
Hepatic function abnormal ^† 1	1/83 (1.20%)	0/82 (0.00%)
Hepatic pain ^† 1	1/83 (1.20%)	2/82 (2.44%)
Infections and infestations
Anal abscess ^† 1	1/83 (1.20%)	0/82 (0.00%)
Catheter related infection ^† 1	1/83 (1.20%)	0/82 (0.00%)
Liver abscess ^† 1	0/83 (0.00%)	1/82 (1.22%)
Pneumonia ^† 1	0/83 (0.00%)	1/82 (1.22%)
Varicella ^† 1	1/83 (1.20%)	0/82 (0.00%)
Injury, poisoning and procedural complications
Accident ^† 1	0/83 (0.00%)	1/82 (1.22%)
Facial bones fracture ^† 1	0/83 (0.00%)	1/82 (1.22%)
Humerus fracture ^† 1	0/83 (0.00%)	1/82 (1.22%)
Joint sprain ^† 1	0/83 (0.00%)	1/82 (1.22%)
Road traffic accident ^† 1	0/83 (0.00%)	1/82 (1.22%)
Spinal compression fracture ^† 1	1/83 (1.20%)	0/82 (0.00%)
Stent occlusion ^† 1	0/83 (0.00%)	1/82 (1.22%)
Therapeutic agent toxicity ^† 1	0/83 (0.00%)	1/82 (1.22%)
Traumatic brain injury ^† 1	0/83 (0.00%)	1/82 (1.22%)
Investigations
Haemoglobin decreased ^† 1	0/83 (0.00%)	1/82 (1.22%)
Lipase increased ^† 1	1/83 (1.20%)	0/82 (0.00%)
Metabolism and nutrition disorders
Acidosis ^† 1	0/83 (0.00%)	1/82 (1.22%)
Dehydration ^† 1	0/83 (0.00%)	1/82 (1.22%)
Hypercalcaemia ^† 1	0/83 (0.00%)	1/82 (1.22%)
Hyperkalaemia ^† 1	1/83 (1.20%)	0/82 (0.00%)
Hypoglycaemia ^† 1	0/83 (0.00%)	2/82 (2.44%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/83 (0.00%)	2/82 (2.44%)
Bone pain ^† 1	1/83 (1.20%)	0/82 (0.00%)
Neck pain ^† 1	0/83 (0.00%)	1/82 (1.22%)
Pain in extremity ^† 1	0/83 (0.00%)	1/82 (1.22%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion ^† 1	0/83 (0.00%)	1/82 (1.22%)
Nervous system disorders
Cerebral haematoma ^† 1	1/83 (1.20%)	0/82 (0.00%)
Cerebrovascular accident ^† 1	0/83 (0.00%)	1/82 (1.22%)
Convulsion ^† 1	0/83 (0.00%)	1/82 (1.22%)
Headache ^† 1	1/83 (1.20%)	0/82 (0.00%)
Hepatic encephalopathy ^† 1	1/83 (1.20%)	1/82 (1.22%)
Leukoencephalopathy ^† 1	1/83 (1.20%)	0/82 (0.00%)
Somnolence ^† 1	0/83 (0.00%)	1/82 (1.22%)
Renal and urinary disorders
Renal failure ^† 1	2/83 (2.41%)	0/82 (0.00%)
Renal failure acute ^† 1	0/83 (0.00%)	1/82 (1.22%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/83 (1.20%)	0/82 (0.00%)
Haemoptysis ^† 1	1/83 (1.20%)	0/82 (0.00%)
Pleurisy ^† 1	0/83 (0.00%)	1/82 (1.22%)
Pulmonary embolism ^† 1	0/83 (0.00%)	2/82 (2.44%)
Vascular disorders
Deep vein thrombosis ^† 1	0/83 (0.00%)	1/82 (1.22%)
Hypertension ^† 1	1/83 (1.20%)	0/82 (0.00%)
Hypotension ^† 1	0/83 (0.00%)	2/82 (2.44%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (12.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sunitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	80/83 (96.39%)	70/82 (85.37%)
Blood and lymphatic system disorders
Anaemia ^† 1	4/83 (4.82%)	8/82 (9.76%)
Leukopenia ^† 1	8/83 (9.64%)	1/82 (1.22%)
Neutropenia ^† 1	23/83 (27.71%)	3/82 (3.66%)
Thrombocytopenia ^† 1	13/83 (15.66%)	4/82 (4.88%)
Endocrine disorders
Hypothyroidism ^† 1	6/83 (7.23%)	1/82 (1.22%)
Eye disorders
Eyelid oedema ^† 1	6/83 (7.23%)	0/82 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	23/83 (27.71%)	23/82 (28.05%)
Abdominal pain upper ^† 1	10/83 (12.05%)	6/82 (7.32%)
Aphthous stomatitis ^† 1	5/83 (6.02%)	2/82 (2.44%)
Constipation ^† 1	12/83 (14.46%)	16/82 (19.51%)
Diarrhoea ^† 1	48/83 (57.83%)	32/82 (39.02%)
Dry mouth ^† 1	7/83 (8.43%)	5/82 (6.10%)
Dyspepsia ^† 1	12/83 (14.46%)	5/82 (6.10%)
Flatulence ^† 1	5/83 (6.02%)	2/82 (2.44%)
Gingival bleeding ^† 1	7/83 (8.43%)	0/82 (0.00%)
Haemorrhoids ^† 1	5/83 (6.02%)	0/82 (0.00%)
Nausea ^† 1	36/83 (43.37%)	24/82 (29.27%)
Oral pain ^† 1	5/83 (6.02%)	0/82 (0.00%)
Stomatitis ^† 1	18/83 (21.69%)	2/82 (2.44%)
Vomiting ^† 1	28/83 (33.73%)	24/82 (29.27%)
General disorders
Asthenia ^† 1	28/83 (33.73%)	22/82 (26.83%)
Chest pain ^† 1	5/83 (6.02%)	5/82 (6.10%)
Chills ^† 1	8/83 (9.64%)	2/82 (2.44%)
Fatigue ^† 1	27/83 (32.53%)	21/82 (25.61%)
Mucosal inflammation ^† 1	13/83 (15.66%)	6/82 (7.32%)
Oedema ^† 1	5/83 (6.02%)	2/82 (2.44%)
Oedema peripheral ^† 1	10/83 (12.05%)	11/82 (13.41%)
Pyrexia ^† 1	9/83 (10.84%)	7/82 (8.54%)
Infections and infestations
Urinary tract infection ^† 1	6/83 (7.23%)	3/82 (3.66%)
Investigations
Blood alkaline phosphatase increased ^† 1	3/83 (3.61%)	6/82 (7.32%)
Weight decreased ^† 1	13/83 (15.66%)	9/82 (10.98%)
Metabolism and nutrition disorders
Anorexia ^† 1	18/83 (21.69%)	17/82 (20.73%)
Decreased appetite ^† 1	5/83 (6.02%)	4/82 (4.88%)
Hypoalbuminaemia ^† 1	2/83 (2.41%)	7/82 (8.54%)
Hypoglycaemia ^† 1	8/83 (9.64%)	2/82 (2.44%)
Hypokalaemia ^† 1	5/83 (6.02%)	2/82 (2.44%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	12/83 (14.46%)	5/82 (6.10%)
Back pain ^† 1	10/83 (12.05%)	14/82 (17.07%)
Muscle spasms ^† 1	5/83 (6.02%)	4/82 (4.88%)
Musculoskeletal pain ^† 1	6/83 (7.23%)	8/82 (9.76%)
Pain in extremity ^† 1	8/83 (9.64%)	5/82 (6.10%)
Nervous system disorders
Dizziness ^† 1	5/83 (6.02%)	5/82 (6.10%)
Dysgeusia ^† 1	17/83 (20.48%)	4/82 (4.88%)
Headache ^† 1	15/83 (18.07%)	11/82 (13.41%)
Psychiatric disorders
Depression ^† 1	2/83 (2.41%)	5/82 (6.10%)
Insomnia ^† 1	15/83 (18.07%)	10/82 (12.20%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	7/83 (8.43%)	7/82 (8.54%)
Dyspnoea ^† 1	10/83 (12.05%)	12/82 (14.63%)
Epistaxis ^† 1	17/83 (20.48%)	4/82 (4.88%)
Oropharyngeal pain ^† 1	6/83 (7.23%)	2/82 (2.44%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	5/83 (6.02%)	1/82 (1.22%)
Dry skin ^† 1	12/83 (14.46%)	9/82 (10.98%)
Erythema ^† 1	8/83 (9.64%)	4/82 (4.88%)
Hair colour changes ^† 1	24/83 (28.92%)	1/82 (1.22%)
Hyperhidrosis ^† 1	3/83 (3.61%)	6/82 (7.32%)
Nail disorder ^† 1	8/83 (9.64%)	1/82 (1.22%)
Palmar-plantar erythrodysaesthesia syndrome ^† 1	19/83 (22.89%)	2/82 (2.44%)
Pruritus ^† 1	4/83 (4.82%)	9/82 (10.98%)
Rash ^† 1	15/83 (18.07%)	4/82 (4.88%)
Yellow skin ^† 1	6/83 (7.23%)	0/82 (0.00%)
Vascular disorders
Hypertension ^† 1	22/83 (26.51%)	4/82 (4.88%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (12.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

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

Results Point of Contact

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Name/Title:	Pfizer ClinicalTrials.gov Call Center
Organization:	Pfizer, Inc.
Phone:	1-800-718-1021
EMail:	ClinicalTrials.govCallCenter@pfizer.com

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

Fazio N, Kulke M, Rosbrook B, Fernandez K, Raymond E. Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib. Target Oncol. 2021 Jan;16(1):27-35. doi: 10.1007/s11523-020-00784-0. Epub 2021 Jan 7.

Lamarca A, Barriuso J, Kulke M, Borbath I, Lenz HJ, Raoul JL, Meropol NJ, Lombard-Bohas C, Posey J, Faivre S, Raymond E, Valle JW. Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response. Br J Cancer. 2018 Jan;118(2):181-188. doi: 10.1038/bjc.2017.402. Epub 2017 Nov 21.

Vinik A, Bottomley A, Korytowsky B, Bang YJ, Raoul JL, Valle JW, Metrakos P, Horsch D, Mundayat R, Reisman A, Wang Z, Chao RC, Raymond E. Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial. Target Oncol. 2016 Dec;11(6):815-824. doi: 10.1007/s11523-016-0462-5.

Faivre S, Niccoli P, Castellano D, Valle JW, Hammel P, Raoul JL, Vinik A, Van Cutsem E, Bang YJ, Lee SH, Borbath I, Lombard-Bohas C, Metrakos P, Smith D, Chen JS, Ruszniewski P, Seitz JF, Patyna S, Lu DR, Ishak KJ, Raymond E. Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study. Ann Oncol. 2017 Feb 1;28(2):339-343. doi: 10.1093/annonc/mdw561.

Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Horsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):501-13. doi: 10.1056/NEJMoa1003825. Erratum In: N Engl J Med. 2011 Mar 17;364(11):1082.

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Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier:	NCT00428597
Other Study ID Numbers:	A6181111
First Submitted:	January 29, 2007
First Posted:	January 30, 2007
Results First Submitted:	April 15, 2010
Results First Posted:	October 11, 2010
Last Update Posted:	October 11, 2010

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