A Study Of SU011248 As Therapy In Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00113516

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if SU011248 (sunitinib) provides additional benefit when it is given after treatment with two chemotherapy drugs carboplatin and paclitaxel and also if sunitinib is safe for patients with locally advanced and metastatic Non Small Cell Lung Cancer (NSCLC).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: carboplatin Drug: paclitaxel Drug: sunitinib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 2 Study Of SU011248 As Consolidation Therapy In Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Mar 1, 2009

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: carboplatin AUC of 6 mgmin/mL via IV infusion every 21 days for 4 cycles as per institutional practices. Other Names: Paraplatin Drug: paclitaxel* 175-225 mg/m2 via IV infusion every 21 days for 4 cycles as per institutional practices. Other Names: Taxol Drug: sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks off treatment up to 1 year (after completing 1 year of treatment, pts deriving clinical benefit may continue to receive sunitinib in a separate continuation protocol). Other Names: SUTENT, SU011248

Arm

Intervention/Treatment

Experimental: 1

Drug: carboplatin

AUC of 6 mg*min/mL via IV infusion every 21 days for 4 cycles as per institutional practices.

Other Names:

Paraplatin

Drug: paclitaxel

175-225 mg/m2 via IV infusion every 21 days for 4 cycles as per institutional practices.

Other Names:

Taxol

Drug: sunitinib

50 mg orally daily for 4 weeks followed by 2 weeks off treatment up to 1 year (after completing 1 year of treatment, pts deriving clinical benefit may continue to receive sunitinib in a separate continuation protocol).

Other Names:

SUTENT, SU011248

Outcome Measures

Primary Outcome Measures

Proportion of Subjects Surviving at One Year [From start of treatment until 1 year or death]
Proportion of those surviving at the end of one year from the first dose of study treatment. In the absence of confirmation of death, survival time was censored at the last date the subject was known to be alive. Patients lacking data beyond the day of first dose had their survival time censored at Day 1 of treatment.

Secondary Outcome Measures

Progression-free Survival (PFS) [From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib) or death]
PFS was defined as the time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date - first paclitaxel/carboplatin dose date +1)/7.02.
Time to Tumor Progression (TTP) [From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib)]
TTP was defined as the time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date - first paclitaxel/carboplatin dose date +1)/7.02.
Duration of Response (DR) [From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib) or death]
DR=time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) that was subsequently confirmed to first documentation of objective disease progression or death due to any cause, whichever was first. CR=disappearance of all target lesions. PR=a > = 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. If tumor progression data included more than 1 date, first date was used. DR (in weeks) was calculated as (the end date for DR - first CR or PR that was subsequently confirmed +1)/7.02.
Number of Subjects With Overall Confirmed Objective Disease Response [From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib)]
Objective disease response = subjects with confirmed CR or PR according to the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.0). 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.
Overall Survival (OS) [From start of study treatment until death]
OS was defined as the time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death - date of paclitaxel/carboplatin first dose +1)/30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of paclitaxel/carboplatin had their survival time censored at Day 1 of paclitaxel/carboplatin treatment.
Trough Plasma Concentration (Ctrough) of Sunitinib [predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2]
Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval.
Ctrough of SU-012662 (Sunitinib's Metabolite) [predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2]
Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval.
Ctrough of Total Drug (Sunitinib + SU-012662) [predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2]
Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval.
Dose-Corrected Ctrough of Sunitinib [predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2]
Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included.
Dose-Corrected Ctrough of SU-012662 (Sunitinib's Metabolite) [predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2]
Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included.
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662) [predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2]
Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included.
Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Concentration at Baseline [Baseline (Cycle 1, Day 1) of Part 2]
Concentration of VEGFR3 at baseline.
VEGFR3 Ratio to Baseline at Each Time Point [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
VEGFR3 concentration at each time point divided by VEGFR3 concentration at baseline (ratio to baseline).
VEGF-C Concentration at Baseline [Baseline (Cycle 1, Day 1) of Part 2]
Concentration of VEGF-C at baseline.
VEGF-C Ratio to Baseline at Each Time Point [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline).
Soluble E-Selectin at Baseline [Baseline (Cycle 1, Day 1) of Part 2]
Concentration of soluble E-Selectin at baseline.
Soluble E-Selectin Ratio to Baseline at Each Time Point [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2]
Soluble E-Selectin concentration at each time point divided by soluble E-Selectin concentration at baseline (ratio to baseline).
VEGFR3 at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD) [Baseline (Cycle 1, Day 1) of Part 2]
Median concentration of VEGFR3 at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality).
VEGFR3 Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD) [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
Median VEGFR3 concentration at each time point divided by median VEGFR3 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
VEGF-C at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD) [Baseline (Cycle 1, Day 1) of Part 2]
Median concentration of VEGF-C at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality).
VEGF-C Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD) [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
Median VEGF-C concentration at each time point divided by median VEGF-C concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
Soluble E-Selectin at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD) [Baseline (Cycle 1, Day 1) of Part 2]
Median concentration of soluble E-selectin at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality).
Soluble E-Selectin Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD) [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2]
Median soluble E-selectin concentration at each time point divided by median soluble E-selectin concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1)divided by 7.02. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after Stratification by < or > = median changes from Baseline in VEGFR3 at each time point.
Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point.
Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline [[Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2]
PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point.
Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after stratification by < or > = median changes from baseline in VEGFR3 at each time point.
Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point.
Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2]
TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point.
Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
OS = time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death minus date of sunitinib first dose +1)divided by 30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after stratification by < or > = median changes from Baseline in VEGFR3 at each time point.
Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2]
OS = time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death minus date of sunitinib first dose +1) divided by 30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point.
Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2]
OS=time from start of study treatment to death due to any cause. OS (in months) calculated as (date of death minus date of sunitinib first dose +1) divided by 30.4. For subjects not expiring their survival times were censored at last date of known contact they were known to be alive. Subjects lacking data beyond day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point.
Immunohistochemical Staining of Paraffin Embedded Tumor Tissue [Screening]
Previously collected tumor paraffin block (or 12-20 10-micron slides prepared for the paraffin block) for correlative laboratory analysis.
Correlation of Polymorphisms in c-Kit, Flt-3 and c-Fms to Safety of Sunitinib [Within 7 days of Day 1]
A blood sample (6 mL) was collected and used to isolate DNA. These samples were not anonymized.
Change From Baseline in Health Related Quality of Life (HRQOL) and Lung Cancer Related Symptoms as Assessed With the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [Baseline (Part 1) to Cycle1 (Days 1 [baseline], 28), Cycles 2 and 3 (Days 1, 28), and Cycle 4 (Day 1) in Part 2]
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. Change: score at each visit in Part 2 minus baseline score in Part 1.
Change From Baseline in HRQOL and Lung Cancer Related Symptoms as Assessed With the EORTC QLQ Lung Cancer Module (QLQ-LC13) [Baseline (Part 1) to Cycle1 (Days 1 [baseline], 28), Cycles 2 and 3 (Days 1, 28), and Cycle 4 (Day 1) in Part 2]
QLQ-LC13 assessed lung cancer symptoms (dyspnea, coughing, dysphasia, hemoptysis, sore mouth, peripheral neuropathy, alopecia, chest pain, arm pain, shoulder pain, and pain in other parts). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. Change: score at each visit in Part 2 minus baseline score in Part 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically proven NSCLC
Stage IIIB (locally advanced with malignant effusion) or Stage IV disease
No prior therapy for NSCLC
Evidence of unidimensionally measurable disease

Exclusion Criteria:

Previous treatment with systemic chemotherapy for lung cancer
History of or known brain metastases
NCI CTCAE Grade 3 hemorrhage within 4 weeks of starting study treatment
Evidence of hemoptysis within 4 weeks of starting study treatment
Serious acute or chronic illness or recent history of significant cardiac abnormality
Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors of EGFR and PDGFR

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Los Angeles	California	United States	90048
2	Pfizer Investigational Site	Newark	Delaware	United States	19713
3	Pfizer Investigational Site	Newark	Delaware	United States	19718
4	Pfizer Investigational Site	Wilmington	Delaware	United States	19899
5	Pfizer Investigational Site	Maywood	Illinois	United States	60153
6	Pfizer Investigational Site	Jeffersonville	Indiana	United States	47130
7	Pfizer Investigational Site	Louisville	Kentucky	United States	40202
8	Pfizer Investigational Site	Louisville	Kentucky	United States	40217
9	Pfizer Investigational Site	Louisville	Kentucky	United States	40241
10	Pfizer Investigational Site	Shelbyville	Kentucky	United States	40065
11	Pfizer Investigational Site	Hershey	Pennsylvania	United States	17033
12	Pfizer Investigational Site	Franklin	Tennessee	United States	37067
13	Pfizer Investigational Site	Gallatin	Tennessee	United States	37066
14	Pfizer Investigational Site	Hermitage	Tennessee	United States	37076
15	Pfizer Investigational Site	Lebanon	Tennessee	United States	37087
16	Pfizer Investigational Site	Murfreesboro	Tennessee	United States	37130
17	Pfizer Investigational Site	Nashville	Tennessee	United States	37203-1632
18	Pfizer Investigational Site	Nashville	Tennessee	United States	37203
19	Pfizer Investigational Site	Nashville	Tennessee	United States	37205
20	Pfizer Investigational Site	Nashville	Tennessee	United States	37207
21	Pfizer Investigational Site	Nashville	Tennessee	United States	37211
22	Pfizer Investigational Site	Smyrna	Tennessee	United States	37167
23	Pfizer Investigational Site	Burleson	Texas	United States	76028
24	Pfizer Investigational Site	Cleburne	Texas	United States	76031
25	Pfizer Investigational Site	Fort Worth	Texas	United States	76104
26	Pfizer Investigational Site	Mineral Wells	Texas	United States	76067
27	Pfizer Investigational Site	Weatherford	Texas	United States	76086
28	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V5Z4E6
29	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 4M1
30	Pfizer Investigational Site	Caen Cedex 05		France	14076
31	Pfizer Investigational Site	Villejuif		France	94805

Sponsors and Collaborators

Pfizer

Investigators

Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00113516

Other Study ID Numbers:

A6181057

First Posted:

Jun 9, 2005

Last Update Posted:

May 18, 2010

Last Verified:

May 1, 2010

Keywords provided by , ,

Lung Neoplasms

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Paclitaxel

Carboplatin

Sunitinib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	During Part 1, subjects received carboplatin plus paclitaxel 172-225 mg/m2. Those same subjects were eligible for continuation in Part 2 where they received sunitinib 50 mg. 66 subjects continued in Part 2.

Arm/Group Title	Carboplatin Plus Paclitaxel	Sunitinib
Arm/Group Description	Carboplatin Plus Paclitaxel 172-225 mg/m2	Sunitinib 50 mg
Period Title: Part 1
STARTED	84	0
COMPLETED	0	0
NOT COMPLETED	84	0
Period Title: Part 1
STARTED	0	66
COMPLETED	0	0
NOT COMPLETED	0	66

Baseline Characteristics

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Overall Participants	84
Age, Customized (participants) [Number]
< 65 years	53 63.1%
> = 65 years	31 36.9%
Sex: Female, Male (Count of Participants)
Female	31 36.9%
Male	53 63.1%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Surviving at One Year
Description	Proportion of those surviving at the end of one year from the first dose of study treatment. In the absence of confirmation of death, survival time was censored at the last date the subject was known to be alive. Patients lacking data beyond the day of first dose had their survival time censored at Day 1 of treatment.
Time Frame	From start of treatment until 1 year or death

Outcome Measure Data

Analysis Population Description
Intent-to-treat (ITT) population = all subjects enrolled in the study who received at least 1 dose of paclitaxel/carboplatin.

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Number [proportion]	0.405

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	The study was designed to test the null hypothesis that the true one-year probability of survival is 0.40 versus the alternative hypothesis that the true one-year probability of survival is at least 0.55. The sample size was determined using a One-Sample Survival design, assuming alpha=0.05 (1-sided), power= 0.90, 6 month accrual, a minimum follow-up period of 12 months, and an expectation that approximately 5% of subjects may be lost to follow-up.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	probability
	Estimated Value	0.405
	Confidence Interval	(2-Sided) 90% 0.315 to 0.494
	Parameter Dispersion	Type: Value:
	Estimation Comments	The probability of survival along with the corresponding confidence interval (CI) (for the log [-log (1-year survival rate)]) was calculated using a normal approximation and then back transformed to give a CI for the 1-year survival rate itself.

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS was defined as the time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date - first paclitaxel/carboplatin dose date +1)/7.02.
Time Frame	From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib) or death

Outcome Measure Data

Analysis Population Description
ITT

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Median (95% Confidence Interval) [weeks]	23.1

3. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	TTP was defined as the time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date - first paclitaxel/carboplatin dose date +1)/7.02.
Time Frame	From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib)

Outcome Measure Data

Analysis Population Description
ITT

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Median (95% Confidence Interval) [weeks]	23.6

4. Secondary Outcome

Title	Duration of Response (DR)
Description	DR=time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) that was subsequently confirmed to first documentation of objective disease progression or death due to any cause, whichever was first. CR=disappearance of all target lesions. PR=a > = 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. If tumor progression data included more than 1 date, first date was used. DR (in weeks) was calculated as (the end date for DR - first CR or PR that was subsequently confirmed +1)/7.02.
Time Frame	From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib) or death

Outcome Measure Data

Analysis Population Description
ITT. DR was calculated for the subgroup of subjects with objective response. 23 subjects reported CR or PR response and were analyzed for DR.

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	23
Median (95% Confidence Interval) [weeks]	27.3

5. Secondary Outcome

Title	Number of Subjects With Overall Confirmed Objective Disease Response
Description	Objective disease response = subjects with confirmed CR or PR according to the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.0). 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 start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib)

Outcome Measure Data

Analysis Population Description
ITT

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Number [participants]	23 27.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	27.4
	Confidence Interval	(2-Sided) 95% 18.2 to 38.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death - date of paclitaxel/carboplatin first dose +1)/30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of paclitaxel/carboplatin had their survival time censored at Day 1 of paclitaxel/carboplatin treatment.
Time Frame	From start of study treatment until death

Outcome Measure Data

Analysis Population Description
ITT

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Median (95% Confidence Interval) [months]	10.4

7. Secondary Outcome

Title	Trough Plasma Concentration (Ctrough) of Sunitinib
Description	Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval.
Time Frame	predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) = all subjects enrolled in the study who received at least 1 dose of carboplatin/paclitaxel or sunitinib. Subjects with plasma values below limit of quantification were excluded.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	66
Cycle 1, Day 28 (n=51)	57.69 (29.37)
Cycle 2, Day 28 (n=36)	50.88 (33.67)
Cycle 3, Day 28 (n=16)	41.55 (24.28)
Cycle 5, Day 28 (n=6)	38.57 (21.83)

8. Secondary Outcome

Title	Ctrough of SU-012662 (Sunitinib's Metabolite)
Description	Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval.
Time Frame	predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Outcome Measure Data

Analysis Population Description
PK. Subjects with plasma values below limit of quantification were excluded.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	66
Cycle 1, Day 28 (n=51)	27.54 (15.10)
Cycle 2, Day 28 (n=36)	23.47 (20.99)
Cycle 3, Day 28 (n=16)	18.37 (9.05)
Cycle 5, Day 28 (n=6)	15.67 (7.12)

9. Secondary Outcome

Title	Ctrough of Total Drug (Sunitinib + SU-012662)
Description	Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval.
Time Frame	predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Outcome Measure Data

Analysis Population Description
PK. Subjects with plasma values below limit of quantification were excluded.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	66
Cycle 1, Day 28 (n=51)	85.23 (42.22)
Cycle 2, Day 28 (n=36)	74.35 (51.60)
Cycle 3, Day 28 (n=16)	59.92 (30.72)
Cycle 5, Day 28 (n=6)	54.24 (27.90)

10. Secondary Outcome

Title	Dose-Corrected Ctrough of Sunitinib
Description	Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included.
Time Frame	predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Outcome Measure Data

Analysis Population Description
PK. Subjects with plasma values below limit of quantification were excluded.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	66
Cycle 1, Day 28 (n=39)	64.10 (26.84)
Cycle 2, Day 28 (n=28)	59.85 (40.45)
Cycle 3, Day 28 (n=13)	49.59 (21.86)
Cycle 5, Day 28 (n=5)	54.51 (13.67)

11. Secondary Outcome

Title	Dose-Corrected Ctrough of SU-012662 (Sunitinib's Metabolite)
Description	Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included.
Time Frame	predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Outcome Measure Data

Analysis Population Description
PK. Subjects with plasma values below limit of quantification were excluded.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	66
Cycle 1, Day 28 (n=39)	27.90 (14.66)
Cycle 2, Day 28 (n=28)	27.37 (30.55)
Cycle 3, Day 28 (n=13)	20.64 (9.97)
Cycle 5, Day 28 (n=5)	22.29 (8.35)

12. Secondary Outcome

Title	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Description	Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included.
Time Frame	predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Outcome Measure Data

Analysis Population Description
PK. Subjects with plasma values below limit of quantification were excluded.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	66
Cycle 1, Day 28 (n=39)	92.00 (40.31)
Cycle 2, Day 28 (n=28)	87.22 (68.28)
Cycle 3, Day 28 (n=13)	70.24 (28.71)
Cycle 5, Day 28 (n=5)	76.80 (20.13)

13. Secondary Outcome

Title	Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Concentration at Baseline
Description	Concentration of VEGFR3 at baseline.
Time Frame	Baseline (Cycle 1, Day 1) of Part 2

Outcome Measure Data

Analysis Population Description
Modified ITT population (MITT) = all subjects enrolled in the study who received at least 1 dose of paclitaxel/carboplatin and at least 1 dose of Sunitinib.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	60
Mean (Standard Deviation) [picograms (pg)/milliliter (mL)]	30382.83 (19134.12)

14. Secondary Outcome

Title	VEGFR3 Ratio to Baseline at Each Time Point
Description	VEGFR3 concentration at each time point divided by VEGFR3 concentration at baseline (ratio to baseline).
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers at baseline and at the specified time point.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	46
Cycle 1, Day 28 (n=46)	0.39 (0.201)
Cycle 2, Day 1 (n=40)	0.74 (0.255)
Cycle 2, Day 28 (n=29)	0.36 (0.165)
Cycle 3, Day 1 (n=21)	0.70 (0.288)
Cycle 3, Day 28 (n=12)	0.31 (0.111)
Cycle 5, Day 28 (n=4)	0.31 (0.163)

15. Secondary Outcome

Title	VEGF-C Concentration at Baseline
Description	Concentration of VEGF-C at baseline.
Time Frame	Baseline (Cycle 1, Day 1) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. Number of participants analyzed = number of subjects with VEGF-C data at Baseline.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	59
Mean (Standard Deviation) [pg/mL]	793.19 (323.770)

16. Secondary Outcome

Title	VEGF-C Ratio to Baseline at Each Time Point
Description	VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline).
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers at baseline and at the specified time point.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	46
Cycle 1, Day 28 (n=46)	0.81 (0.342)
Cycle 2, Day 1 (n=39)	0.90 (0.396)
Cycle 2, Day 28 (n=30)	0.91 (0.577)
Cycle 3, Day 1 (n=20)	1.00 (0.460)
Cycle 3, Day 28 (n=12)	0.91 (0.340)
Cycle 5, Day 28 (n=4)	0.89 (0.269)

17. Secondary Outcome

Title	Soluble E-Selectin at Baseline
Description	Concentration of soluble E-Selectin at baseline.
Time Frame	Baseline (Cycle 1, Day 1) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. Number of participants analyzed = number of subjects with soluble E-Selectin data at Baseline.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	53
Mean (Standard Deviation) [nanograms (ng)/mL]	27.06 (11.474)

18. Secondary Outcome

Title	Soluble E-Selectin Ratio to Baseline at Each Time Point
Description	Soluble E-Selectin concentration at each time point divided by soluble E-Selectin concentration at baseline (ratio to baseline).
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers at baseline and at the specified time point. At Cycle 4, Day 28, median and/or standard deviation were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	34
Cycle 1, Day 28 (n=34)	0.83 (0.222)
Cycle 2, Day 1 (n=29)	0.89 (0.287)
Cycle 2, Day 28 (n=22)	0.77 (0.246)
Cycle 3, Day 1 (n=16)	0.81 (0.224)
Cycle 3, Day 28 (n=8)	0.69 (0.126)
Cycle 5, Day 28 (n=3)	0.76 (0.354)

19. Secondary Outcome

Title	VEGFR3 at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
Description	Median concentration of VEGFR3 at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline (Cycle 1, Day 1) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers and tumor response at baseline.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	45
Cycle 1, Day 1 (CR or PR or SD, n=21)	21660.00
Cycle 1, Day 1 (PD, n=24)	27740.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.474
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

20. Secondary Outcome

Title	VEGFR3 Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
Description	Median VEGFR3 concentration at each time point divided by median VEGFR3 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers at baseline and at the specified time point. No subjects had PD at Cycle 5, Day 28.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	36
Cycle 1, Day 28 (CR or PR or SD, n=16)	0.34
Cycle 1, Day 28 (PD, n=20)	0.35
Cycle 2, Day 1 (CR or PR or SD, n=19)	0.75
Cycle 2, Day 1 (PD, n=16)	0.84
Cycle 2, Day 28 (CR or PR or SD, n=15)	0.32
Cycle 2, Day 28 (PD, n=12)	0.38
Cycle 3, Day 1 (CR or PR or SD, n=15)	0.57
Cycle 3, Day 1 (PD, n=5)	0.92
Cycle 3, Day 28 (CR or PR or SD, n=11)	0.38
Cycle 3, Day 28 (pd, n=1)	0.43
Cycle 5, Day 28 (CR or PR or SD, n=4)	0.30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.836
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.071
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.393
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.247
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

21. Secondary Outcome

Title	VEGF-C at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
Description	Median concentration of VEGF-C at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline (Cycle 1, Day 1) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers and tumor response at baseline.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	44
Cycle 1, Day 1 (CR or PR or SD, n=20)	704.80
Cycle 1, Day 1 (PD, n=24)	766.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.305
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

22. Secondary Outcome

Title	VEGF-C Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
Description	Median VEGF-C concentration at each time point divided by median VEGF-C concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. No subjects had PD at Cycle 5, Day 28.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	36
Cycle 1, Day 28 (CR or PR or SD, n=16)	0.73
Cycle 1, Day 28 (PD, n=20)	0.81
Cycle 2, Day 1 (CR or PR or SD, n=18)	0.87
Cycle 2, Day 1 (PD, n=16)	0.85
Cycle 2, Day 28 (CR or PR or SD, n=16)	0.89
Cycle 2, Day 28 (PD, n=12)	0.69
Cycle 3, Day 1 (CR or PR or SD, n=14)	0.89
Cycle 3, Day 1 (PD, n=5)	0.78
Cycle 3, Day 28 (CR or PR or SD, n=11)	0.85
Cycle 3, Day 28 (PD, n=1)	0.90
Cycle 5, Day 28 (CR or PR or SD, n=4)	0.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.738
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.438
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.236
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.287
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.772
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

23. Secondary Outcome

Title	Soluble E-Selectin at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
Description	Median concentration of soluble E-selectin at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline (Cycle 1, Day 1) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with levels of soluble protein biomarkers and tumor response at baseline.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	38
Cycle 1, Day 1 (CR or PR or SD, n=17)	26.40
Cycle 1, Day 1 (PD, n=21)	27.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.537
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

24. Secondary Outcome

Title	Soluble E-Selectin Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
Description	Median soluble E-selectin concentration at each time point divided by median soluble E-selectin concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. No subjects had PD at Cycle 4, Day 28 and Cycle 5, Day 28.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	26
Cycle 1, Day 28 (CR or PR or SD, n=10)	0.84
Cycle 1, Day 28 (PD, n=16)	0.84
Cycle 2, Day 1 (CR or PR or SD, n=13)	0.84
Cycle 2, Day 1 (PD, n=12)	0.76
Cycle 2, Day 28 (CR or PR or SD, n=10)	0.86
Cycle 2, Day 28 (PD, n=10)	0.64
Cycle 3, Day 1 (CR or PR or SD, n=10)	0.74
Cycle 3, Day 1 (PD, n=5)	0.77
Cycle 3, Day 28 (CR or PR or SD, n=7)	0.67
Cycle 3, Day 28 (PD, n=1)	0.78
Cycle 4, Day 28 (CR or PR or SD, n=1)	1.13
Cycle 5, Day 28 (CR or PR or SD, n=3)	0.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.813
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.849
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.121
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.582
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.383
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

25. Secondary Outcome

Title	Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline
Description	PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1)divided by 7.02. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after Stratification by < or > = median changes from Baseline in VEGFR3 at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 28 (< median cutpoint) and Cycle 5, Day 28 (> = median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	60
Cycle 1, Day 1 (< Median Cutpoint, n=30)	13.1
Cycle 1, Day 1 (> = Median Cutpoint, n=30)	10.3
Cycle 1, Day 28 (< Median Cutpoint, n=23)	15.8
Cycle 1, Day 28 (> = Median Cutpoint, n=23)	10.3
Cycle 2, Day 1 (< Median Cutpoint, n=20)	22.5
Cycle 2, Day 1 (> = Median Cutpoint, n=20)	11.1
Cycle 2, Day 28 (< Median Cutpoint, n=14)	16.8
Cycle 2, Day 28 (> = Median Cutpoint, n=15)	16.1
Cycle 3, Day 1 (< Median Cutpoint, n=10)	32.9
Cycle 3, Day 1 (> = Median Cutpoint, n=11)	16.1
Cycle 3, Day 28 (> = Median Cutpoint, n=6)	32.9
Cycle 5, Day 28 (< Median Cutpoint, n=2)	38.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6782
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95% 0.61 to 2.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1980
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95% 0.77 to 3.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1344
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95% 0.82 to 3.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4809
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% 0.56 to 3.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0153
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95% 1.19 to 11.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2085
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95% 0.52 to 14.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 5, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8084
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% 0.08 to 23.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group

26. Secondary Outcome

Title	Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline
Description	PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 28 (< median cutpoint) and Cycle 5, Day 28 (< median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	59
Cycle 1, Day 1 (< Median Cutpoint, n=29)	16.1
Cycle 1, Day 1 (> = Median Cutpoint, n=30)	10.1
Cycle 1, Day 28 (< Median Cutpoint, n=23)	12.4
Cycle 1, Day 28 (> = Median Cutpoint, n=23)	11.0
Cycle 2, Day 1 (< Median Cutpoint, n=19)	13.1
Cycle 2, Day 1 (> = Median Cutpoint, n=20)	16.1
Cycle 2, Day 28 (< Median Cutpoint, n=15)	10.8
Cycle 2, Day 28 (> = Median Cutpoint, n=15)	31.8
Cycle 3, Day 1 (< Median Cutpoint, n=10)	19.7
Cycle 3, Day 1 (> = Median Cutpoint, n=10)	30.8
Cycle 3, Day 28 (> = Median Cutpoint, n=6)	32.9
Cycle 5, Day 28 (> = Median Cutpoint, n=2)	37.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5070
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95% 0.65 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4474
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95% 0.63 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7599
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95% 0.40 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0109
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95% 0.12 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6878
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95% 0.43 to 3.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4637
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95% 0.38 to 8.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

27. Secondary Outcome

Title	Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline
Description	PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point.
Time Frame	[Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 2, Day 28 (> = median cutpoint), Cycle 3, Day 28 (< median cutpoint), and Cycles 4 and 5, Day 28 (< median cutpoint, > = median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	53
Cycle 1, Day 1 (< Median Cutpoint, n=26)	11.1
Cycle 1, Day 1 (> = Median Cutpoint, n=27)	11.0
Cycle 1, Day 28 (< Median Cutpoint, n=17)	11.0
Cycle 1, Day 28 (> = Median Cutpoint, n=17)	10.1
Cycle 2, Day 1 (< Median Cutpoint, n=14)	11.0
Cycle 2, Day 1 (> = Median Cutpoint, n=15)	16.1
Cycle 2, Day 28 (< Median Cutpoint, n=11)	11.0
Cycle 3, Day 1 (< Median Cutpoint, n=8)	33.8
Cycle 3, Day 1 (> = Median Cutpoint, n=8)	22.5
Cycle 3, Day 28 (> = Median Cutpoint, n=4)	43.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5277
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95% 0.39 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4660
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% 0.58 to 3.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of >=Median Cutpoint group hazard to <Median Cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5337
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95% 0.52 to 3.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of >=Median Cutpoint group hazard to <Median Cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0712
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95% 0.13 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of >=Median Cutpoint group hazard to <Median Cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2948
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95% 0.54 to 7.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of >=Median Cutpoint group hazard to <Median Cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3200
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95% 0.28 to 38.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of >=Median Cutpoint group hazard to <Median Cutpoint group.

28. Secondary Outcome

Title	Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline
Description	TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after stratification by < or > = median changes from baseline in VEGFR3 at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 28 (< median cutpoint) and Cycle 5, Day 28 (> = median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	60
Cycle 1, Day 1 (< Median Cutpoint, n=30)	15.8
Cycle 1, Day 1 (> = Median Cutpoint, n=30)	11.0
Cycle 1, Day 28 (< Median Cutpoint, n=23)	15.8
Cycle 1, Day 28 (> = Median Cutpoint, n=23)	12.4
Cycle 2, Day 1 (< Median Cutpoint, n=20)	30.8
Cycle 2, Day 1 (> = Median Cutpoint, n=20)	11.1
Cycle 2, Day 28 (< Median Cutpoint, n=14)	16.8
Cycle 2, Day 28 (> = Median Cutpoint, n=15)	16.1
Cycle 3, Day 1 (< Median Cutpoint, n=10)	32.9
Cycle 3, Day 1 (> = Median Cutpoint, n=11)	16.1
Cycle 3, Day 28 (> = Median Cutpoint, n=6)	32.9
Cycle 5, Day 28 (< Median Cutpoint, n=2)	38.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7824
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95% 0.56 to 2.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1918
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95% 0.77 to 3.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1093
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95% 0.85 to 4.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4809
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% 0.56 to 3.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0110
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95% 1.26 to 13.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2085
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95% 0.52 to 14.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 5, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8084
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% 0.08 to 23.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

29. Secondary Outcome

Title	Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline
Description	TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 28 (< median cutpoint), and Cycle 5, Day 28 (< median cutpoint, > = median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	59
Cycle 1, Day 1 (< Median Cutpoint, n=29)	16.1
Cycle 1, Day 1 (> = Median Cutpoint, n=30)	10.3
Cycle 1, Day 28 (< Median Cutpoint, n=23)	15.8
Cycle 1, Day 28 (> = Median Cutpoint, n=23)	11.0
Cycle 2, Day 1 (< Median Cutpoint, n=19)	13.1
Cycle 2, Day 1 (> = Median Cutpoint, n=20)	16.1
Cycle 2, Day 28 (< Median Cutpoint, n=15)	10.8
Cycle 2, Day 28 (> = Median Cutpoint, n=15)	31.8
Cycle 3, Day 1 (< Median Cutpoint, n=10)	16.8
Cycle 3, Day 1 (> = Median Cutpoint, n=10)	30.8
Cycle 3, Day 28 (> = Median Cutpoint, n=6)	32.9
Cycle 5, Day 28 (> = Median Cutpoint, n=2)	37.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5215
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95% 0.62 to 2.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2504
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95% 0.72 to 3.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8766
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95% 0.42 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0109
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95% 0.12 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5627
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95% 0.46 to 4.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4637
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95% 0.38 to 8.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

30. Secondary Outcome

Title	Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline Changes From Baseline
Description	TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 2, Day 28 (> = median cutpoint), Cycle 3, Day 28 (< median cutpoint), and Cycles 4 and 5, Day 28 (< median cutpoint, > = median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	53
Cycle 1, Day 1 (< Median Cutpoint, n=26)	11.1
Cycle 1, Day 1 (> = Median Cutpoint, n=27)	12.4
Cycle 1, Day 28 (< Median Cutpoint, n=17)	11.0
Cycle 1, Day 28 (> = Median Cutpoint, n=17)	10.1
Cycle 2, Day 1 (< Median Cutpoint, n=14)	11.0
Cycle 2, Day 1 (> = Median Cutpoint, n=15)	16.1
Cycle 2, Day 28 (< Median Cutpoint, n=11)	11.0
Cycle 3, Day 1 (< Median Cutpoint, n=8)	33.8
Cycle 3, Day 1 (> = Median Cutpoint n=8)	33.9
Cycle 3, Day 28 (> = Median Cutpoint, n=4)	43.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6682
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95% 0.39 to 1.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6854
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95% 0.49 to 3.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6028
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95% 0.49 to 3.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0712
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95% 0.13 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3411
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95% 0.50 to 7.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3200
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95% 0.28 to 38.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

31. Secondary Outcome

Title	Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline Changes From Baseline
Description	OS = time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death minus date of sunitinib first dose +1)divided by 30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after stratification by < or > = median changes from Baseline in VEGFR3 at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 1 (< median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	60
Cycle 1, Day 1 (< Median Cutpoint, n=30)	8.7
Cycle 1, Day 1 (> = Median Cutpoint, n=30)	6.1
Cycle 1, Day 28 (< Median Cutpoint, n=23)	14.7
Cycle 1, Day 28 (> = Median Cutpoint, n=23)	7.1
Cycle 2, Day 1 (< Median Cutpoint, n=20)	13.7
Cycle 2, Day 1 (> = Median Cutpoint, n=20)	8.8
Cycle 2, Day 28 (< Median Cutpoint, n=14)	11.2
Cycle 2, Day 28 (> = Median Cutpoint, n=15)	13.3
Cycle 3, Day 1 (> = Median Cutpoint, n=11)	7.4
Cycle 3, Day 28 (< Median Cutpoint, n=6)	17.7
Cycle 5, Day 28 (< Median Cutpoint, n=2)	17.1
Cycle 5, Day 28 (> = Median Cutpoint, n=2)	13.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4768
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95% 0.70 to 2.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1484
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95% 0.84 to 3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8957
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95% 0.50 to 2.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5681
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95% 0.33 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0074
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 95% 1.35 to 10.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1637
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95% 0.06 to 1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 5, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4328
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95% 0.23 to 29.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

32. Secondary Outcome

Title	Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline
Description	OS = time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death minus date of sunitinib first dose +1) divided by 30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 28 (> = median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	59
Cycle 1, Day 1 (< Median Cutpoint, n=29)	8.5
Cycle 1, Day 1 (> = Median Cutpoint, n=30)	5.2
Cycle 1, Day 28 (< Median Cutpoint, n=23)	8.5
Cycle 1, Day 28 (> = Median Cutpoint, n=23)	8.8
Cycle 2, Day 1 (< Median Cutpoint, n=19)	9.7
Cycle 2, Day 1 (> = Median Cutpoint, n=20)	12.7
Cycle 2, Day 28 (< Median Cutpoint, n=15)	8.0
Cycle 2, Day 28 (> = Median Cutpoint, n=15)	14.8
Cycle 3, Day 1 (< Median Cutpoint, n=10)	10.2
Cycle 3, Day 1 (> = Median Cutpoint, n=10)	15.8
Cycle 3, Day 28 (< Median Cutpoint, n=6)	14.2
Cycle 5, Day 28 (< Median Cutpoint, n=2)	14.2
Cycle 5, Day 28 (> = Median Cutpoint, n=2)	16.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4269
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95% 0.72 to 2.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9290
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95% 0.51 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8195
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95% 0.44 to 1.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2210
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95% 0.26 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4297
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95% 0.24 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0522
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95% 0.06 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 5, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6949
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95% 0.05 to 7.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

33. Secondary Outcome

Title	Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline
Description	OS=time from start of study treatment to death due to any cause. OS (in months) calculated as (date of death minus date of sunitinib first dose +1) divided by 30.4. For subjects not expiring their survival times were censored at last date of known contact they were known to be alive. Subjects lacking data beyond day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point.
Time Frame	Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Outcome Measure Data

Analysis Population Description
MITT. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point. At Cycle 3, Day 1 (< median cutpoint), Cycle 4, Day 28 (< median cutpoint, > = median cutpoint)and Cycle 5, Day 28 (< median cutpoint), median and/or CI were not able to be estimated.

Arm/Group Title	Sunitinib
Arm/Group Description	Part 2 = Sunitinib 50 mg
Measure Participants	53
Cycle 1, Day 1 (< Median Cutpoint, n=26)	6.5
Cycle 1, Day 1 (> = Median Cutpoint, n=27)	8.0
Cycle 1, Day 28 (< Median Cutpoint, n=17)	8.7
Cycle 1, Day 28 (> = Median Cutpoint, n=17)	6.5
Cycle 2, Day 1 (< Median Cutpoint, n=14)	11.2
Cycle 2, Day 1 (> = Median Cutpoint, n=15)	8.5
Cycle 2, Day 28 (< Median Cutpoint, n=11)	8.0
Cycle 2, Day 28 (> = Median Cutpoint, n=11)	14.8
Cycle 3, Day 1 (> = Median Cutpoint, n=8)	12.7
Cycle 3, Day 28 (> = Median Cutpoint, n=4)	15.3
Cycle 5, Day 28 (> = Median Cutpoint, n=2)	13.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7660
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95% 0.51 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 1, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2682
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95% 0.72 to 3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2726
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95% 0.69 to 3.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 2, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2787
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95% 0.22 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 1
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0241
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95% 1.09 to 17.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 3, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0943
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95% 0.59 to 48.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	First Carboplatin Plus Paclitaxel, Then Sunitinib
	Comments	Cycle 5, Day 28
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8084
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95% 0.04 to 11.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based upon the ratio of > = median cutpoint group hazard to < median cutpoint group.

34. Secondary Outcome

Title	Immunohistochemical Staining of Paraffin Embedded Tumor Tissue
Description	Previously collected tumor paraffin block (or 12-20 10-micron slides prepared for the paraffin block) for correlative laboratory analysis.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description
Samples were collected and stained from a subset of subjects. Due to the small sample size, no correlative analyses with clinical outcome were conducted.

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	0

35. Secondary Outcome

Title	Correlation of Polymorphisms in c-Kit, Flt-3 and c-Fms to Safety of Sunitinib
Description	A blood sample (6 mL) was collected and used to isolate DNA. These samples were not anonymized.
Time Frame	Within 7 days of Day 1

Outcome Measure Data

Analysis Population Description
c-Kit, Flt-3 and c-Fms to safety of Sunitinib samples were collected and analyzed. However, there was no statistics performed since power was insufficient.

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	0

36. Secondary Outcome

Title	Change From Baseline in Health Related Quality of Life (HRQOL) and Lung Cancer Related Symptoms as Assessed With the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
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. Change: score at each visit in Part 2 minus baseline score in Part 1.
Time Frame	Baseline (Part 1) to Cycle1 (Days 1 [baseline], 28), Cycles 2 and 3 (Days 1, 28), and Cycle 4 (Day 1) in Part 2

Outcome Measure Data

Analysis Population Description
ITT. Number of participants analyzed = number of subjects with EORTC response (defined as having at least 1 item response on the EORTC). n=number of subjects with EORTC scale score at baseline and each specified time point. Data in cycles with less than 9 subjects are not reported due to lack of statistical reliability.

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Cycle 1, Day 1 Global Health Status /QoL (n=54)	-1.54 (3.580)
Cycle 1, Day 28 Global Health Status /QoL (n=42)	-9.13 (3.964)
Cycle 2, Day 1 Global Health Status /QoL (n=35)	-2.62 (3.361)
Cycle 2, Day 28 Global Health Status /QoL (n=21)	-9.13 (4.704)
Cycle 3, Day 1 Global Health Status /QoL (n=14)	0.60 (7.175)
Cycle 3, Day 28 Global Health Status /QoL (n=10)	-2.50 (8.056)
Cycle 4, Day 1 Global Health Status /QoL (n=10)	7.50 (4.883)
Cycle 1, Day 1 Physical Functioning (n=54)	-6.79 (2.806)
Cycle 1, Day 28 Physical Functioning (n=42)	-9.68 (2.363)
Cycle 2, Day 1 Physical Functioning (n=35)	-7.43 (2.941)
Cycle 2, Day 28 Physical Functioning (n=22)	-12.42 (4.771)
Cycle 3, Day 1 Physical Functioning (n=15)	-5.78 (3.178)
Cycle 3, Day 28 Physical Functioning (n=10)	-9.33 (7.647)
Cycle 4, Day 1 Physical Functioning (n=10)	-2.00 (5.072)
Cycle 1, Day 1 Role Functioning (n=54)	-16.05 (4.641)
Cycle 1, Day 28 Role Functioning (n=42)	-20.63 (5.383)
Cycle 2, Day 1 Role Functioning (n=35)	-13.81 (4.950)
Cycle 2, Day 28 Role Functioning (n=22)	-28.03 (8.234)
Cycle 3, Day 1 Role Functioning (n=15)	-16.67 (7.968)
Cycle 3, Day 28 Role Functioning (n=10)	-15.00 (13.017)
Cycle 4, Day 1 Role Functioning (n=10)	8.33 (11.180)
Cycle 1, Day 1 Emotional Functioning (n=54)	-2.16 (3.512)
Cycle 1, Day 28 Emotional Functioning (n=42)	3.57 (3.139)
Cycle 2, Day 1 Emotional Functioning (n=35)	1.90 (3.649)
Cycle 2, Day 28 Emotional Functioning (n=21)	1.98 (4.668)
Cycle 3, Day 1 Emotional Functioning (n=14)	13.10 (3.571)
Cycle 3, Day 28 Emotional Functioning (n=10)	12.50 (4.348)
Cycle 4, Day 1 Emotional Functioning (n=10)	24.17 (5.038)
Cycle 1, Day 1 Cognitive Functioning (n=54)	-8.95 (3.138)
Cycle 1, Day 28 Cognitive Functioning (n=42)	-3.57 (3.704)
Cycle 2, Day 1 Cognitive Functioning (n=35)	-10.00 (3.817)
Cycle 2, Day 28 Cognitive Functioning (n=21)	-10.32 (5.573)
Cycle 3, Day 1 Cognitive Functioning (n=14)	1.19 (3.692)
Cycle 3, Day 28 Cognitive Functioning (n=10)	-1.67 (4.615)
Cycle 4, Day 1 Cognitive Functioning (n=10)	5.00 (5.000)
Cycle 1, Day 1 Social Functioning (n=53)	-11.64 (4.250)
Cycle 1, Day 28 Social Functioning (n=41)	-10.98 (5.417)
Cycle 2, Day 1 Social Functioning (n=34)	-9.31 (5.228)
Cycle 2, Day 28 Social Functioning (n=20)	-25.00 (7.204)
Cycle 3, Day 1 Social Functioning (n=14)	-7.14 (5.980)
Cycle 3, Day 28 Social Functioning (n=10)	-8.33 (11.453)
Cycle 4, Day 1 Social Functioning (n=10)	1.67 (7.222)
Cycle 1, Day 1 Fatigue (n=54)	13.48 (3.411)
Cycle 1, Day 28 Fatigue (n=42)	16.40 (3.921)
Cycle 2, Day 1 Fatigue (n=35)	8.25 (4.083)
Cycle 2, Day 28 Fatigue (n=22)	19.70 (6.025)
Cycle 3, Day 1 Fatigue (n=15)	8.15 (6.548)
Cycle 3, Day 28 Fatigue (n=10)	22.22 (11.355)
Cycle 4, Day 1 Fatigue (n=10)	-1.11 (7.490)
Cycle 1, Day 1 Nausea and Vomiting (n=54)	5.56 (2.988)
Cycle 1, Day 28 Nausea and Vomiting (n=42)	11.90 (3.822)
Cycle 2, Day 1 Nausea and Vomiting (n=35)	6.67 (4.491)
Cycle 2, Day 28 Nausea and Vomiting (n=22)	6.82 (4.608)
Cycle 3, Day 1 Nausea and Vomiting (n=15)	5.56 (5.789)
Cycle 3, Day 28 Nausea and Vomiting (n=10)	11.67 (7.049)
Cycle 4, Day 1 Nausea and Vomiting (n=10)	1.67 (6.310)
Cycle 1, Day 1 Pain (n=54)	3.09 (4.228)
Cycle 1, Day 28 Pain (n=42)	-0.79 (3.766)
Cycle 2, Day 1 Pain (n=35)	5.24 (4.572)
Cycle 2, Day 28 Pain (n=22)	0.76 (5.748)
Cycle 3, Day 1 Pain (n=15)	5.56 (6.640)
Cycle 3, Day 28 Pain (n=10)	-1.67 (8.767)
Cycle 4, Day 1 Pain (n=10)	-3.33 (7.778)
Cycle 1, Day 1 Dyspnea (n=54)	2.47 (3.396)
Cycle 1, Day 28 Dyspnea (n=42)	1.59 (3.760)
Cycle 2, Day 1 Dyspnea (n=35)	-4.76 (4.352)
Cycle 2, Day 28 Dyspnea (n=22)	-13.64 (6.454)
Cycle 3, Day 1 Dyspnea (n=15)	-8.89 (3.940)
Cycle 3, Day 28 Dyspnea (n=10)	0.00 (8.607)
Cycle 4, Day 1 Dyspnea (n=10)	-13.33 (7.370)
Cycle 1, Day 1 Insomnia (n=54)	-3.09 (5.006)
Cycle 1, Day 28 Insomnia (n=42)	-5.56 (5.671)
Cycle 2, Day 1 Insomnia (n=35)	-2.86 (5.529)
Cycle 2, Day 28 Insomnia (n=22)	6.06 (8.672)
Cycle 3, Day 1 Insomnia (n=15)	-2.22 (6.057)
Cycle 3, Day 28 Insomnia (n=10)	6.67 (10.887)
Cycle 4, Day 1 Insomnia (n=10)	-20.00 (7.370)
Cycle 1, Day 1 Appetite Loss (n=54)	11.11 (5.138)
Cycle 1, Day 28 Appetite Loss (n=42)	20.63 (5.898)
Cycle 2, Day 1 Appetite Loss (n=35)	13.33 (7.633)
Cycle 2, Day 28 Appetite Loss (n=22)	10.61 (7.068)
Cycle 3, Day 1 Appetite Loss (n=15)	2.22 (7.606)
Cycle 3, Day 28 Appetite Loss (n=10)	13.3 (12.373)
Cycle 4, Day 1 Appetite Loss (n=10)	-6.67 (10.887)
Cycle 1, Day 1 Constipation (n=54)	5.56 (4.109)
Cycle 1, Day 28 Constipation (n=42)	-0.79 (5.266)
Cycle 2, Day 1 Constipation (n=35)	13.33 (4.965)
Cycle 2, Day 28 Constipation (n=22)	-4.55 (6.317)
Cycle 3, Day 1 Constipation (n=15)	-4.44 (6.397)
Cycle 3, Day 28 Constipation (n=10)	-6.67 (6.667)
Cycle 4, Day 1 Constipation (n=10)	-10.00 (5.092)
Cycle 1, Day 1 Diarrhea (n=54)	-3.09 (2.206)
Cycle 1, Day 28 Diarrhea (n=41)	13.01 (5.058)
Cycle 2, Day 1 Diarrhea (n=35)	11.43 (4.916)
Cycle 2, Day 28 Diarrhea (n=21)	7.94 (5.589)
Cycle 3, Day 1 Diarrhea (n=14)	16.67 (6.767)
Cycle 3, Day 28 Diarrhea (n=10)	26.67 (9.686)
Cycle 4, Day 1 Diarrhea (n=10)	0.00 (9.938)
Cycle 1, Day 1 Financial Difficulties (n=54)	5.56 (2.607)
Cycle 1, Day 28 Financial Difficulties (n=42)	2.38 (2.381)
Cycle 2, Day 1 Financial Difficulties (n=34)	5.88 (4.331)
Cycle 2, Day 28 Financial Difficulties (n=21)	6.35 (5.453)
Cycle 3, Day 1 Financial Difficulties (n=14)	11.90 (7.500)
Cycle 3, Day 28 Financial Difficulties (n=10)	13.33 (10.184)
Cycle 4, Day 1 Financial Difficulties (n=10)	13.33 (10.184)

37. Secondary Outcome

Title	Change From Baseline in HRQOL and Lung Cancer Related Symptoms as Assessed With the EORTC QLQ Lung Cancer Module (QLQ-LC13)
Description	QLQ-LC13 assessed lung cancer symptoms (dyspnea, coughing, dysphasia, hemoptysis, sore mouth, peripheral neuropathy, alopecia, chest pain, arm pain, shoulder pain, and pain in other parts). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. Change: score at each visit in Part 2 minus baseline score in Part 1.
Time Frame	Baseline (Part 1) to Cycle1 (Days 1 [baseline], 28), Cycles 2 and 3 (Days 1, 28), and Cycle 4 (Day 1) in Part 2

Outcome Measure Data

Analysis Population Description
ITT. Number of participants analyzed = number of subjects with EORTC response (defined as having at least 1 item response on the EORTC). n=number of subjects with EORTC scale score at baseline and each specified time point. Data in cycles with less than 9 subjects are not reported due to lack of statistical reliability.

Arm/Group Title	First Carboplatin Plus Paclitaxel, Then Sunitinib
Arm/Group Description	Part 1 = Carboplatin plus Paclitaxel 172-225 mg/m2. Part 2 = Sunitinib 50 mg
Measure Participants	84
Cycle 1, Day 1 Dyspnea (n=49)	3.40 (3.008)
Cycle 1, Day 28 Dyspnea (n=37)	4.80 (3.030)
Cycle 2, Day 1 Dyspnea (n=31)	4.30 (4.112)
Cycle 2, Day 28 Dyspnea (n=21)	1.59 (4.490)
Cycle 3, Day 1 Dyspnea (n=14)	-1.59 (3.466)
Cycle 3, Day 28 Dyspnea (n=9)	4.94 (6.705)
Cycle 4, Day 1 Dyspnea (n=9)	0.00 (3.208)
Cycle 1, Day 1 Coughing (n=53)	-14.47 (5.120)
Cycle 1, Day 28 Coughing (n=40)	-14.17 (5.048)
Cycle 2, Day 1 Coughing (n=34)	-12.75 (5.077)
Cycle 2, Day 28 Coughing (n=21)	-15.87 (7.496)
Cycle 3, Day 1 Coughing (n=14)	-9.52 (5.445)
Cycle 3, Day 28 Coughing (n=10)	-13.33 (7.370)
Cycle 4, Day 1 Coughing (n=9)	-11.11 (7.857)
Cycle 1, Day 1 Hemoptysis (n=53)	0.63 (1.678)
Cycle 1, Day 28 Hemoptysis (n=39)	5.13 (3.362)
Cycle 2, Day 1 Hemoptysis (n=33)	2.02 (1.406)
Cycle 2, Day 28 Hemoptysis (n=21)	-1.59 (2.795)
Cycle 3, Day 1 Hemoptysis (n=14)	-2.38 (2.381)
Cycle 3, Day 28 Hemoptysis (n=10)	0.00 (0.000)
Cycle 4, Day 1 Hemoptysis (n=9)	-3.70 (3.704)
Cycle 1, Day 1 Sore Mouth (n=53)	-5.66 (3.782)
Cycle 1, Day 28 Sore Mouth (n=40)	20.00 (7.141)
Cycle 2, Day 1 Sore Mouth (n=34)	9.80 (7.111)
Cycle 2, Day 28 Sore Mouth (n=21)	12.70 (6.289)
Cycle 3, Day 1 Sore Mouth (n=14)	0.00 (3.494)
Cycle 3, Day 28 Sore Mouth (n=10)	10.00 (13.194)
Cycle 4, Day 1 Sore Mouth (n=9)	-11.11 (7.857)
Cycle 1, Day 1 Dysphasia (n=53)	-0.63 (3.298)
Cycle 1, Day 28 Dysphasia (n=40)	7.50 (4.697)
Cycle 2, Day 1 Dysphasia (n=34)	2.94 (5.145)
Cycle 2, Day 28 Dysphasia (n=21)	-1.59 (2.795)
Cycle 3, Day 1 Dysphasia (n=14)	-4.76 (4.762)
Cycle 3, Day 28 Dysphasia (n=10)	-10.00 (5.092)
Cycle 4, Day 1 Dysphasia (n=9)	-11.11 (5.556)
Cycle 1, Day 1 Peripheral Neuropathy (n=53)	42.14 (5.012)
Cycle 1, Day 28 Peripheral Neuropathy (n=40)	32.50 (5.402)
Cycle 2, Day 1 Peripheral Neuropathy (n=34)	28.43 (5.825)
Cycle 2, Day 28 Peripheral Neuropathy (n=21)	26.98 (7.841)
Cycle 3, Day 1 Peripheral Neuropathy (n=14)	23.81 (10.145)
Cycle 3, Day 28 Peripheral Neuropathy (n=10)	20.00 (10.184)
Cycle 4, Day 1 Peripheral Neuropathy (n=9)	7.41 (7.407)
Cycle 1, Day 1 Alopecia (n=53)	63.52 (5.407)
Cycle 1, Day 28 Alopecia (n=40)	40.83 (7.009)
Cycle 2, Day 1 Alopecia (n=34)	30.39 (7.627)
Cycle 2, Day 28 Alopecia (n=20)	11.67 (7.752)
Cycle 3, Day 1 Alopecia (n=14)	0.00 (0.000)
Cycle 3, Day 28 Alopecia (n=10)	0.00 (0.000)
Cycle 4, Day 1 Alopecia (n=9)	0.00 (0.000)
Cycle 1, Day 1 Pain in Chest (n=53)	-8.18 (3.581)
Cycle 1, Day 28 Pain in Chest (n=40)	-4.17 (3.415)
Cycle 2, Day 1 Pain in Chest (n=34)	-0.98 (3.850)
Cycle 2, Day 28 Pain in Chest (n=21)	0.00 (3.984)
Cycle 3, Day 1 Pain in Chest (n=14)	4.76 (5.906)
Cycle 3, Day 28 Pain in Chest (n=10)	0.00 (7.027)
Cycle 4, Day 1 Pain in Chest (n=9)	7.41 (9.259)
Cycle 1, Day 1 Pain in Arm or Shoulder (n=51)	-1.31 (4.171)
Cycle 1, Day 28 Pain in Arm or Shoulder (n=39)	0.85 (4.497)
Cycle 2, Day 1 Pain in Arm or Shoulder (n=34)	3.92 (6.257)
Cycle 2, Day 28 Pain in Arm or Shoulder (n=21)	3.17 (4.545)
Cycle 3, Day 1 Pain in Arm or Shoulder (n=14)	2.38 (4.228)
Cycle 3, Day 28 Pain in Arm or Shoulder (n=10)	-6.67 (11.967)
Cycle 4, Day 1 Pain in Arm or Shoulder (n=9)	-11.11 (11.111)
Cycle 1, Day 1 Pain in Other Parts (n=47)	3.55 (6.431)
Cycle 1, Day 28 Pain in Other Parts (n=35)	-6.67 (5.925)
Cycle 2, Day 1 Pain in Other Parts (n=27)	12.35 (7.368)
Cycle 2, Day 28 Pain in Other Parts (n=17)	13.73 (8.603)
Cycle 3, Day 1 Pain in Other Parts (n=14)	11.90 (8.274)
Cycle 3, Day 28 Pain in Other Parts (n=9)	-11.11 (9.623)
Cycle 4, Day 1 Pain in Other Parts (n=9)	0.00 (9.623)

Adverse Events

Arm/Group Description
Time Frame
Adverse Event Reporting Description	Part 1 = adverse events (AEs) reported occurred during chemotherapy treatment. Part 2 = AEs reported occurred on or after the first dose of sunitinib.

Arm/Group Title	Carboplatin Plus Paclitaxel 172-225 mg/m2 (Part 1)		Sunitinib 50 mg (Part 2)
All Cause Mortality
	Carboplatin Plus Paclitaxel 172-225 mg/m2 (Part 1)		Sunitinib 50 mg (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Carboplatin Plus Paclitaxel 172-225 mg/m2 (Part 1)		Sunitinib 50 mg (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/84 (34.5%)		29/66 (43.9%)
Blood and lymphatic system disorders
Neutropenia	2/84 (2.4%)		0/66 (0%)
Pancytopenia	2/84 (2.4%)		0/66 (0%)
Thrombocytopenia	0/84 (0%)		4/66 (6.1%)
Cardiac disorders
Atrial fibrillation	1/84 (1.2%)		0/66 (0%)
Pericardial effusion	1/84 (1.2%)		0/66 (0%)
Pericarditis	1/84 (1.2%)		0/66 (0%)
Tachycardia	1/84 (1.2%)		0/66 (0%)
Cardiac failure	0/84 (0%)		1/66 (1.5%)
Myocardial ischaemia	0/84 (0%)		1/66 (1.5%)
Endocrine disorders
Adrenal insufficiency	0/84 (0%)		2/66 (3%)
Gastrointestinal disorders
Vomiting	4/84 (4.8%)		2/66 (3%)
Abdominal pain	1/84 (1.2%)		1/66 (1.5%)
Diarrhoea	1/84 (1.2%)		0/66 (0%)
Gastritis	1/84 (1.2%)		0/66 (0%)
Nausea	1/84 (1.2%)		2/66 (3%)
Haematemesis	0/84 (0%)		1/66 (1.5%)
Lower gastrointestinal haemorrhage	0/84 (0%)		1/66 (1.5%)
Subileus	0/84 (0%)		1/66 (1.5%)
General disorders
Chest pain	4/84 (4.8%)		2/66 (3%)
Pyrexia	2/84 (2.4%)		1/66 (1.5%)
Asthenia	1/84 (1.2%)		3/66 (4.5%)
Disease progression	1/84 (1.2%)		7/66 (10.6%)
Extravasation	1/84 (1.2%)		0/66 (0%)
General physical health deterioration	1/84 (1.2%)		0/66 (0%)
Fatigue	0/84 (0%)		1/66 (1.5%)
Mucosal inflammation	0/84 (0%)		1/66 (1.5%)
Pain	0/84 (0%)		1/66 (1.5%)
Immune system disorders
Anaphylactic reaction	1/84 (1.2%)		0/66 (0%)
Hypersensitivity	1/84 (1.2%)		0/66 (0%)
Infections and infestations
Pneumonia	3/84 (3.6%)		2/66 (3%)
Septic shock	2/84 (2.4%)		0/66 (0%)
Pyelonephritis acute	1/84 (1.2%)		0/66 (0%)
Sinusitis	1/84 (1.2%)		0/66 (0%)
Injury, poisoning and procedural complications
Fall	1/84 (1.2%)		0/66 (0%)
Fracture	1/84 (1.2%)		0/66 (0%)
Hip fracture	1/84 (1.2%)		0/66 (0%)
Investigations
Coagulation time prolonged	0/84 (0%)		1/66 (1.5%)
Metabolism and nutrition disorders
Dehydration	3/84 (3.6%)		1/66 (1.5%)
Hypokalaemia	1/84 (1.2%)		1/66 (1.5%)
Hypercalcaemia	0/84 (0%)		2/66 (3%)
Anorexia	0/84 (0%)		1/66 (1.5%)
Decreased appetite	0/84 (0%)		1/66 (1.5%)
Hypoglycaemia	0/84 (0%)		1/66 (1.5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/84 (1.2%)		0/66 (0%)
Back pain	0/84 (0%)		2/66 (3%)
Nervous system disorders
Sciatica	2/84 (2.4%)		0/66 (0%)
Cerebrovascular accident	0/84 (0%)		2/66 (3%)
Cerebellar syndrome	0/84 (0%)		1/66 (1.5%)
Convulsion	0/84 (0%)		1/66 (1.5%)
Psychiatric disorders
Mental status changes	1/84 (1.2%)		3/66 (4.5%)
Anxiety	0/84 (0%)		2/66 (3%)
Confusional state	0/84 (0%)		2/66 (3%)
Insomnia	0/84 (0%)		1/66 (1.5%)
Renal and urinary disorders
Haemorrhage urinary tract	1/84 (1.2%)		0/66 (0%)
Hydronephrosis	1/84 (1.2%)		0/66 (0%)
Renal failure	0/84 (0%)		2/66 (3%)
Renal failure acute	0/84 (0%)		1/66 (1.5%)
Ureteric obstruction	0/84 (0%)		1/66 (1.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/84 (2.4%)		0/66 (0%)
Pulmonary embolism	2/84 (2.4%)		4/66 (6.1%)
Dyspnoea	1/84 (1.2%)		4/66 (6.1%)
Hypercapnia	1/84 (1.2%)		0/66 (0%)
Pleuritic pain	1/84 (1.2%)		0/66 (0%)
Pneumothorax	1/84 (1.2%)		0/66 (0%)
Tachypnoea	1/84 (1.2%)		0/66 (0%)
Hypoxia	0/84 (0%)		1/66 (1.5%)
Pleural effusion	0/84 (0%)		1/66 (1.5%)
Vascular disorders
Deep vein thrombosis	1/84 (1.2%)		0/66 (0%)
Hypotension	1/84 (1.2%)		0/66 (0%)
Venous thrombosis	1/84 (1.2%)		0/66 (0%)
Haemorrhage	0/84 (0%)		1/66 (1.5%)
Phlebitis superficial	0/84 (0%)		1/66 (1.5%)
Thrombosis	0/84 (0%)		1/66 (1.5%)
Vena cava thrombosis	0/84 (0%)		1/66 (1.5%)
Other (Not Including Serious) Adverse Events
	Carboplatin Plus Paclitaxel 172-225 mg/m2 (Part 1)		Sunitinib 50 mg (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/84 (97.6%)		60/66 (90.9%)
Blood and lymphatic system disorders
Anaemia	28/84 (33.3%)		12/66 (18.2%)
Neutropenia	20/84 (23.8%)		9/66 (13.6%)
Thrombocytopenia	9/84 (10.7%)		13/66 (19.7%)
Leukopenia	0/84 (0%)		4/66 (6.1%)
Lymphopenia	0/84 (0%)		6/66 (9.1%)
Gastrointestinal disorders
Constipation	23/84 (27.4%)		9/66 (13.6%)
Diarrhoea	6/84 (7.1%)		24/66 (36.4%)
Nausea	36/84 (42.9%)		21/66 (31.8%)
Vomiting	21/84 (25%)		12/66 (18.2%)
Abdominal discomfort	0/84 (0%)		4/66 (6.1%)
Abdominal pain	0/84 (0%)		7/66 (10.6%)
Abdominal pain upper	0/84 (0%)		6/66 (9.1%)
Dyspepsia	0/84 (0%)		9/66 (13.6%)
Gastrooesophageal reflux disease	0/84 (0%)		4/66 (6.1%)
General disorders
Asthenia	14/84 (16.7%)		17/66 (25.8%)
Chest pain	6/84 (7.1%)		6/66 (9.1%)
Chills	6/84 (7.1%)		7/66 (10.6%)
Fatigue	27/84 (32.1%)		21/66 (31.8%)
Mucosal inflammation	6/84 (7.1%)		8/66 (12.1%)
Oedema peripheral	12/84 (14.3%)		7/66 (10.6%)
Pain	5/84 (6%)		2/66 (3%)
Pyrexia	17/84 (20.2%)		9/66 (13.6%)
Infections and infestations
Upper respiratory tract infection	0/84 (0%)		6/66 (9.1%)
Investigations
Weight decreased	10/84 (11.9%)		4/66 (6.1%)
Metabolism and nutrition disorders
Anorexia	10/84 (11.9%)		16/66 (24.2%)
Decreased appetite	0/84 (0%)		5/66 (7.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	23/84 (27.4%)		6/66 (9.1%)
Back pain	9/84 (10.7%)		5/66 (7.6%)
Myalgia	22/84 (26.2%)		2/66 (3%)
Pain in extremity	12/84 (14.3%)		4/66 (6.1%)
Musculoskeletal pain	0/84 (0%)		4/66 (6.1%)
Nervous system disorders
Dysgeusia	5/84 (6%)		10/66 (15.2%)
Hypoaesthesia	6/84 (7.1%)		2/66 (3%)
Neuropathy peripheral	24/84 (28.6%)		6/66 (9.1%)
Paraesthesia	8/84 (9.5%)		2/66 (3%)
Peripheral sensory neuropathy	5/84 (6%)		0/66 (0%)
Dizziness	0/84 (0%)		4/66 (6.1%)
Headache	0/84 (0%)		7/66 (10.6%)
Psychiatric disorders
Anxiety	9/84 (10.7%)		0/66 (0%)
Insomnia	11/84 (13.1%)		0/66 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	11/84 (13.1%)		6/66 (9.1%)
Dyspnoea	16/84 (19%)		12/66 (18.2%)
Epistaxis	6/84 (7.1%)		4/66 (6.1%)
Hiccups	5/84 (6%)		0/66 (0%)
Haemoptysis	0/84 (0%)		7/66 (10.6%)
Skin and subcutaneous tissue disorders
Alopecia	40/84 (47.6%)		0/66 (0%)
Rash	8/84 (9.5%)		9/66 (13.6%)
Dry skin	0/84 (0%)		4/66 (6.1%)
Erythema	0/84 (0%)		4/66 (6.1%)
Skin discolouration	0/84 (0%)		4/66 (6.1%)
Skin exfoliation	0/84 (0%)		4/66 (6.1%)
Vascular disorders
Hypertension	0/84 (0%)		9/66 (13.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

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

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00113516

Other Study ID Numbers:

A6181057

First Posted:

Jun 9, 2005

Last Update Posted:

May 18, 2010

Last Verified:

May 1, 2010