Trial Outcomes & Findings for A Clinical Trial Comparing Efficacy And Safety Of Sunitinib Versus Placebo For TheTreatment Of Patients At High Risk Of Recurrent Renal Cell Cancer (NCT NCT00375674)

Last Updated: 2018-09-21

Results Overview

DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by blinded independent central review (BICR) or investigator assessment for respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for remainder of follow-up period unless the participant had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

674 participants

Primary outcome timeframe

Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later.

Results posted on

2018-09-21

Participant Flow

Of 674 enrolled participants (615 in global cohort and 59 in china cohort), the results presented refers to the study conducted on 615 (intent-to-treat population) in 21 countries and were randomized to sunitinib and placebo for 9 cycles (1 cycle=42 days).

Screening: From Week 0 (nephrectomy surgery) to Week 11; in this period, echocardiogram/multi-gated acquisition, post-surgery imaging, histopathology, physical examination, laboratory tests, electrocardiogram and concomitant treatment were assessed. Randomization occurred not before 3 weeks post-nephrectomy \& not after 12 weeks post-nephrectomy.

Participant milestones

Participant milestones
Measure	Sunitinib Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Study STARTED	309	306
Overall Study Intent-to-Treat Population	309	306
Overall Study As-Treated Population	306	304
Overall Study COMPLETED	165	165
Overall Study NOT COMPLETED	144	141

Reasons for withdrawal

Reasons for withdrawal
Measure	Sunitinib Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Study Other	26	18
Overall Study Death	67	76
Overall Study Participants refused further follow-up	31	30
Overall Study Lost to Follow-up	17	15
Overall Study Enrolled but not treated	3	2

Baseline Characteristics

A Clinical Trial Comparing Efficacy And Safety Of Sunitinib Versus Placebo For TheTreatment Of Patients At High Risk Of Recurrent Renal Cell Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Total n=615 Participants Total of all reporting groups
Age, Continuous	56.8 years STANDARD_DEVIATION 10.6 • n=5 Participants	57.9 years STANDARD_DEVIATION 10.6 • n=7 Participants	57.9 years STANDARD_DEVIATION 10.6 • n=5 Participants
Age, Customized <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Between 18 and 65 years	233 Participants n=5 Participants	224 Participants n=7 Participants	457 Participants n=5 Participants
Age, Customized >=65 years	76 Participants n=5 Participants	82 Participants n=7 Participants	158 Participants n=5 Participants
Sex/Gender, Customized Female	87 Participants n=5 Participants	77 Participants n=7 Participants	164 Participants n=5 Participants
Sex/Gender, Customized Male	222 Participants n=5 Participants	229 Participants n=7 Participants	451 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later.

Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review	6.8 Number of years Interval 5.8 to The upper limit of the 95% confidence interval of the median DFS on Sunitinib was not reached	5.6 Number of years Interval 3.8 to 6.6

PRIMARY outcome

DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by BICR or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the participants had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population]	6.5 Number of years Interval 4.7 to 7.0	4.5 Number of years Interval 3.8 to 5.9

SECONDARY outcome

Timeframe: Every 12 weeks until the time for final analysis (up to data cut-off date: 30 April 2017; maximum exposure:14.9 months)

OS was defined as the time from the date of randomization to the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population)	NA Year Data was not estimable due to small number of participants with an event.	NA Year Data was not estimable due to small number of participants with an event.

SECONDARY outcome

Timeframe: Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later

Population: The As-Treated (AT) population included all participants who received at least 1 dose of study drug with treatment assignments designated according to actual study treatment received. This population was the primary population for evaluating treatment administration/ compliance and safety.

TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.

Outcome measures

Outcome measures
Measure	Sunitinib n=306 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=304 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants With Adverse Events (AEs)	305 Number of participants	270 Number of participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants With Serious Adverse Events (SAEs)	67 Number of participants	52 Number of participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants With Grade 3 or 4 AEs	189 Number of participants	61 Number of participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants With Grade 5 AEs	5 Number of participants	5 Number of participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants Discontinued Due to AEs	86 Number of participants	16 Number of participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants With Dose Reduced Due to AEs	106 Number of participants	6 Number of participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Temporary Discontinuation Due to AEs	141 Number of participants	40 Number of participants

SECONDARY outcome

Population: AT population: All participants who received at least 1 dose of study drug with treatment assignments designated according to actual study treatment received. The numbers of participants analyzed were the participants with any adverse event of special interest (AESI) and that one participant could have reported more than one AESI

Outcome measures

Outcome measures
Measure	Sunitinib n=306 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=304 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Benign Neoplasm of Thyroid Gland	—	35.1 Weeks
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Goitre	—	305.6 Weeks Standard Deviation 97.08
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Hyperthyroidism	23.2 Weeks Standard Deviation 25.95	110.8 Weeks Standard Deviation 146.57
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Hypothyroidism	46.9 Weeks Standard Deviation 75.30	58.0 Weeks Standard Deviation 62.06
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Papillary Thyroid Cancer	—	22.1 Weeks
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Thyroid Disorder	19 Weeks	—
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) Thyroid Mass	—	20.4 Weeks

SECONDARY outcome

Timeframe: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.

Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale, 5 multi-item functional scales (physical, role, emotional, cognitive, \& social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, \& pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, \& the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from "not at all" to "very much" to assess functioning \& symptoms; 2 items with 7-point Likert scales for global health \& overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL \& more severe for symptoms.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 1 (Baseline)	74.83 Scores on scale Standard Error 1.044	75.61 Scores on scale Standard Error 1.044
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 2	69.71 Scores on scale Standard Error 1.289	75.49 Scores on scale Standard Error 1.097
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 3	69.67 Scores on scale Standard Error 1.278	74.09 Scores on scale Standard Error 1.142
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 4	66.52 Scores on scale Standard Error 1.307	74.93 Scores on scale Standard Error 1.109
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 5	68.34 Scores on scale Standard Error 1.340	74.61 Scores on scale Standard Error 1.179
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 6	66.27 Scores on scale Standard Error 1.396	75.69 Scores on scale Standard Error 1.172
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 7	67.42 Scores on scale Standard Error 1.447	73.98 Scores on scale Standard Error 1.222
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 8	68.33 Scores on scale Standard Error 1.376	74.49 Scores on scale Standard Error 1.260
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores Cycle 9	68.31 Scores on scale Standard Error 1.556	74.06 Scores on scale Standard Error 1.338
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores End of treatment (EOT)	64.43 Scores on scale Standard Error 1.367	73.37 Scores on scale Standard Error 1.264

SECONDARY outcome

Timeframe: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale \& 5 multi-item functional scales (physical, role, emotional, cognitive, \& social functioning). The questionnaire includes 28 items with 4-point Likert type responses from "not at all" to "very much" to assess functioning; 2 items with 7-point Likert scales for global health \& overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison Physical	83.54 Scores on scale Interval 82.4 to 84.68	87.53 Scores on scale Interval 86.42 to 88.64
PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison Role	78.94 Scores on scale Interval 77.14 to 80.74	85.46 Scores on scale Interval 83.7 to 87.23
PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison Emotional	80.92 Scores on scale Interval 79.58 to 82.27	82.97 Scores on scale Interval 81.66 to 84.29
PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison Cognitive	85.50 Scores on scale Interval 84.17 to 86.83	87.43 Scores on scale Interval 86.13 to 88.73
PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison Social	80.62 Scores on scale Interval 79.04 to 82.21	87.99 Scores on scale Interval 86.44 to 89.53

SECONDARY outcome

Timeframe: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

PROs assessed health-related QoL by using the EORTC QLQ-C30, which was a 30 multi-item symptom scales (fatigue, nausea/vomiting, \& pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, \& the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from "not at all" to "very much" to assess symptoms. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented more severe symptoms.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Fatigue	29.94 Scores on scale Interval 28.33 to 31.56	21.74 Scores on scale Interval 20.16 to 23.31
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Nausea and Vomiting	7.35 Scores on scale Interval 6.38 to 8.33	3.46 Scores on scale Interval 2.51 to 4.41
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Pain	21.81 Scores on scale Interval 20.1 to 23.52	16.63 Scores on scale Interval 14.96 to 18.3
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Dyspnoea	14.97 Scores on scale Interval 13.38 to 16.57	11.89 Scores on scale Interval 10.33 to 13.45
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Insomnia	22.22 Scores on scale Interval 20.26 to 24.19	20.73 Scores on scale Interval 18.81 to 22.65
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Appetite Loss	14.66 Scores on scale Interval 13.12 to 16.21	4.62 Scores on scale Interval 3.11 to 6.13
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Constipation	11.24 Scores on scale Interval 9.66 to 12.82	9.83 Scores on scale Interval 8.29 to 11.37
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Diarrhoea	19.25 Scores on scale Interval 17.54 to 20.95	7.25 Scores on scale Interval 5.59 to 8.91
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison Financial Difficulties	15.12 Scores on scale Interval 13.42 to 16.82	13.92 Scores on scale Interval 12.26 to 15.59

SECONDARY outcome

Timeframe: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.

Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. In this outcome measure, the first part with 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, \& anxiety/depression) was used; a participant was asked to rate each state on a 3-level scale (1=no problem, 2=some problem, \& 3=extreme problem); higher levels indicated greater severity/impairment. The published weights allowed the creation of a single summary score called the EQ-5D index, which ranged from -0.594 to 1; low scores represented a higher level of dysfunction \& 1 as perfect health.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 8	0.80 Units on a scale Standard Error 0.015	0.84 Units on a scale Standard Error 0.013
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 9	0.81 Units on a scale Standard Error 0.015	0.85 Units on a scale Standard Error 0.013
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 1 (Baseline)	0.84 Units on a scale Standard Error 0.011	0.83 Units on a scale Standard Error 0.011
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 2	0.83 Units on a scale Standard Error 0.011	0.84 Units on a scale Standard Error 0.011
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 3	0.80 Units on a scale Standard Error 0.013	0.82 Units on a scale Standard Error 0.012
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 4	0.77 Units on a scale Standard Error 0.014	0.84 Units on a scale Standard Error 0.011
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 5	0.77 Units on a scale Standard Error 0.016	0.84 Units on a scale Standard Error 0.013
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 6	0.78 Units on a scale Standard Error 0.016	0.85 Units on a scale Standard Error 0.012
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population Cycle 7	0.77 Units on a scale Standard Error 0.016	0.83 Units on a scale Standard Error 0.014
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population EOT	0.75 Units on a scale Standard Error 0.017	0.83 Units on a scale Standard Error 0.015

SECONDARY outcome

Timeframe: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.

Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. The first part assessed the current health state. In this outcome measure, the second part was applied to assess the general health status by using visual analog scale (EQ-5D VAS) which measured participant's self-rated health status on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 1 (Baseline)	77.31 Units on a scale Standard Error 0.999	75.67 Units on a scale Standard Error 1.080
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 2	74.39 Units on a scale Standard Error 1.188	76.99 Units on a scale Standard Error 1.080
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 3	74.20 Units on a scale Standard Error 1.093	76.85 Units on a scale Standard Error 1.122
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 4	74.14 Units on a scale Standard Error 1.118	77.34 Units on a scale Standard Error 1.115
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 5	73.30 Units on a scale Standard Error 1.220	77.56 Units on a scale Standard Error 1.212
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 6	73.51 Units on a scale Standard Error 1.250	78.61 Units on a scale Standard Error 1.130
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 7	72.27 Units on a scale Standard Error 1.267	77.49 Units on a scale Standard Error 1.180
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 8	73.96 Units on a scale Standard Error 1.226	77.65 Units on a scale Standard Error 1.213
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means Cycle 9	72.93 Units on a scale Standard Error 1.424	79.02 Units on a scale Standard Error 1.168
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means EOT	71.79 Units on a scale Standard Error 1.139	76.93 Units on a scale Standard Error 1.283

SECONDARY outcome

Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. This table provides the summary of discontinuations de to adverse events. Participants were counted only once in each row.

Outcome measures

Outcome measures
Measure	Sunitinib n=309 Participants Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Placebo n=306 Participants Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Number of Participants With Tolerability Symptoms Pyrexia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Stomatitis	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Vena cava thrombosis	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Metastases to lung	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Gastritis haemorrhagic	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Glossodynia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Hepatic function abnormal	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Hepatitis acute	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Hypercreatininaemia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Hypertransaminasaemia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Hypothyroidism	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Influenza like illness	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Mental status changes	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Mucosal inflammation	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Myalgia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Myocardial infarction	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Myocarditis	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Necrosis	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Nephrotic syndrome	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Neutropenia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Oedema peripheral	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Pancytopenia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Post procedural infection	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Presyncope	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Therapeutic response unexpected	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Tremor	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Vertigo	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Agitated depression	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Angina unstable	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Brain cancer metastatic	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Hepatitis	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Hypersensitivity	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Palmar-plantar erythrodysaesthesia syndrome	13 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Hypertension	6 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Asthenia	4 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Fatigue	3 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Pulmonary embolism	3 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Gastrooesophageal reflux disease	3 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Ejection fraction decreased	2 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Left ventricular dysfunction	2 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Acute myocardial infarction	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Blood creatinine increased	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Dehydration	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Dyspepsia	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Proteinuria	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Thrombocytopenia	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Upper gastrointestinal haemorrhage	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Vomiting	2 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Electrocardiogram QT prolonged	1 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Lethargy	1 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Transient ischaemic attack	1 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Depression	0 Number of participants	2 Number of participants
Number of Participants With Tolerability Symptoms Abdominal pain	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Abdominal pain upper	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Acute kidney injury	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Ageusia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Alanine aminotransferase increased	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Anal inflammation	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Anal pruritus	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Aspartate aminotransferase increased	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Atrial fibrillation	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Atrial flutter	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Diarrhoea	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Disease progression	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Dysgeusia	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Electrocardiogram ST segment abnormal	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Embolism venous	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Eyelid oedema	1 Number of participants	0 Number of participants
Number of Participants With Tolerability Symptoms Mood altered	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Renal impairment	0 Number of participants	1 Number of participants
Number of Participants With Tolerability Symptoms Tinnitus	0 Number of participants	1 Number of participants

Adverse Events

Sunitinib

Serious events: 67 serious events

Other events: 303 other events

Deaths: 67 deaths

Placebo

Serious events: 52 serious events

Other events: 270 other events

Deaths: 76 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1800718

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER