A Study Of AG-013736 (Axitinib) Or Bevacizumab (Avastin) In Combination With Paclitaxel And Carboplatin In Patients With Advanced Lung Cancer.

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00600821
• Collaborator: (none)
• Enrollment: 118
• Locations: 44
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To determine if the addition of AG-013736 to chemotherapy is beneficial in patients with advanced lung cancer who have not been previously treated.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Carcinoma; Adenocarcinoma	Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: AG-013736 (axitinib); Drug: Carboplatin; Drug: Paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase 2 Trial Of AG013736 Or Bevacizumab In Combination With Paclitaxel And Carboplatin As First Line Treatment For Patients With Advanced Non Small Cell Lung Cancer
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: B Bevacizumab will be administered in combination with carboplatin and paclitaxel.	Drug: Bevacizumab; Bevacizumab is available as 100 and 400 mg preservative-free, single use vials- The starting dose is 15 mg/kg, iv infusion, every 3 weeks.; Other Names: Avastin ; Drug: Carboplatin; Carboplatin is available as pre-mixed 10mg /ml aqueous solution- The starting dose is AUC 6 mg*min/ml, iv infusion, every 3 weeks.; Drug: Paclitaxel; Paclitaxel is available in multidose vials (30 mg/5ml;100mg/16.7 ml;300 mg/50ml)- The starting dose is 200 mg/m2, every 3 weeks
Experimental: A AG-013736 will be administered in combination with carboplatin and paclitaxel.	Drug: AG-013736 (axitinib); AG-013736 (axitinib) is available as 1mg, and 5 mg film-coated tablets for oral administration- The starting dose is 5 mg BID-; Other Names: axitinib Taxol ; Drug: Carboplatin; Carboplatin is available as pre-mixed 10mg /ml aqueous solution- The starting dose is AUC 6 mg*min/ml, iv infusion, every 3 weeks.; Drug: Paclitaxel; Paclitaxel is available in multidose vials (30 mg/5ml;100mg/16.7 ml;300 mg/50ml)- The starting dose is 200 mg/m2, every 3 weeks

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years]

   Time in months from start of study treatment to first randomization date of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

Secondary Outcome Measures

1. Overall Survival (OS) [Baseline, every 6 weeks until death or bimonthly after final study visit (up to 2.75 years)]

   Time in months from date of randomization to date of death due to any cause. OS was calculated as (the death date minus the first randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

2. Percentage of Participants With Objective Response (OR) [Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years]

   OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR: disappearance of all lesions (target and/or non target) and no appearance of new lesions. PR: at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, without progression of non target lesions and no appearance of new lesions.

3. Duration of Response (DR) [Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years]

   Time in months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

4. Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736) [Pre-dose, 1 to 2 hours post-dose on Cycle 2 of Day 1 and Cycle 3 of Day 1]

   Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

5. European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score [Day (D) 1 of every cycle (C) then every 3 weeks until final study visit (up to 2.75 years)]

   EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhoea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.

6. European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score [Day 1 of every cycle then every 3 weeks until final study visit (up to 2.75 years)]

   QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnoea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). 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.

7. Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile in Whole Blood [Baseline, C1 D1, C1 D15, C2 D1, C3 D1, C4 D1 and C5 D1]

   RNA expression profiles of genes which were associated with tumor growth, angiogenesis and metastases were collected and correlated with efficacy.

8. Circulating Endothelial Cells (CEC) in Blood: Total CEC [Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1]

   Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs.

9. Circulating Endothelial Cells (CEC) in Blood [Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1]

   Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs.

10. Plasma Concentration of Soluble Proteins [Baseline, C1D1, C1D15, C2D1, C3D1, C4D1, C5D1, C7D1, C9D1 and C11D1]

    Plasma concentrations of soluble proteins (soluble- stem-cell factor receptor (sKIT) vascular endothelial growth factor [VEGF], and vascular endothelial growth factor receptor-2 [VEGFR2], VEGFR3) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline.

Other Outcome Measures

1. Plasma Concentration Change in the Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1) Genotype [Baseline (Day 1 of Cycle 1)]

   UGT1A1 an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Advanced non squamous cell, lung cancer

• No prior treatment for lung cancer except prior adjuvant therapy if last dose was >12 months prior to enrollment

Exclusion Criteria:

• Prior therapy for advanced lung cancer

• The need for blood-thinners

• Coughing up blood

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Baton Rouge	Louisiana	United States	70809
2	Pfizer Investigational Site	Pittsfield	Massachusetts	United States	01201
3	Pfizer Investigational Site	Columbus	Mississippi	United States	39705
4	Pfizer Investigational Site	Corinth	Mississippi	United States	38834
5	Pfizer Investigational Site	New Albany	Mississippi	United States	38652
6	Pfizer Investigational Site	Oxford	Mississippi	United States	38655
7	Pfizer Investigational Site	Southaven	Mississippi	United States	38671
8	Pfizer Investigational Site	Tupelo	Mississippi	United States	38801
9	Pfizer Investigational Site	Lincoln	Nebraska	United States	68510
10	Pfizer Investigational Site	Cleveland	Ohio	United States	44109
11	Pfizer Investigational Site	Bartlett	Tennessee	United States	38133
12	Pfizer Investigational Site	Germantown	Tennessee	United States	38138
13	Pfizer Investigational Site	Memphis	Tennessee	United States	38119
14	Pfizer Investigational Site	Memphis	Tennessee	United States	38120
15	Pfizer Investigational Site	Dallas	Texas	United States	75230
16	Pfizer Investigational Site	Dallas	Texas	United States	75235
17	Pfizer Investigational Site	Dallas	Texas	United States	75246
18	Pfizer Investigational Site	Dallas	Texas	United States	75390-8590
19	Pfizer Investigational Site	Lubbock	Texas	United States	79410
20	Pfizer Investigational Site	San Antonio	Texas	United States	78229
21	Pfizer Investigational Site	San Antonio	Texas	United States	78284
22	Pfizer Investigational Site	Wenatchee	Washington	United States	98801
23	Pfizer Investigational Site	Praha 8		Czech Republic	180 81
24	Pfizer Investigational Site	Tabor		Czech Republic	390 03
25	Pfizer Investigational Site	Usti nad Labem		Czech Republic	401 13
26	Pfizer Investigational Site	Caen Cedex 05		France	14076
27	Pfizer Investigational Site	Paris Cedex 14		France	75679
28	Pfizer Investigational Site	Pierre-Bénite		France	69495
29	Pfizer Investigational Site	Bydgoszcz		Poland	85-796
30	Pfizer Investigational Site	Gdansk		Poland	80-462
31	Pfizer Investigational Site	Gdynia		Poland	81-519
32	Pfizer Investigational Site	Torun		Poland	87 - 100
33	Pfizer Investigational Site	Warszawa		Poland	02-097
34	Pfizer Investigational Site	Mataro	Barcelona	Spain	08304
35	Pfizer Investigational Site	Sabadell	Barcelona	Spain	08208
36	Pfizer Investigational Site	Alicante		Spain	03010
37	Pfizer Investigational Site	Valencia		Spain	46014
38	Pfizer Investigational Site	Southampton	Hampshire	United Kingdom	SO16 6YD
39	Pfizer Investigational Site	Dundee	Scotland	United Kingdom	DD1 9SY
40	Pfizer Investigational Site	Leeds	Yorkshire	United Kingdom	LS9 7TF
41	Pfizer Investigational Site	Dundee		United Kingdom	DD1 9SY
42	Pfizer Investigational Site	London		United Kingdom	NW1 2PG
43	Pfizer Investigational Site	London		United Kingdom	SW3 6JJ
44	Pfizer Investigational Site	Surrey		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00600821
• Other Study ID Numbers: A4061030
• First Posted: Jan 25, 2008
• Last Update Posted: Nov 8, 2013
• Last Verified: Oct 1, 2013

• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Carboplatin; Axitinib

Study Results

Participant Flow

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily (BID) along with infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin area under the concentration-time curve (AUC) of 6 mg*minute/milliliter (mg*min/mL) infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kilogram (mg/kg) infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Period Title: Overall Study
STARTED	58	60
Treated	58	59
COMPLETED	0	0
NOT COMPLETED	58	60

Baseline Characteristics

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin	Total
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.	Total of all reporting groups
Overall Participants	58	60	118
Age, Customized (Number) [Number]
Less than 18 years	0 0%	0 0%	0 0%
18 to 44 years	1 1.7%	2 3.3%	3 2.5%
45 to 64 years	33 56.9%	44 73.3%	77 65.3%
Greater than or equal to 65 years	24 41.4%	14 23.3%	38 32.2%
Sex: Female, Male (Count of Participants)
Female	22 37.9%	23 38.3%	45 38.1%
Male	36 62.1%	37 61.7%	73 61.9%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Time in months from start of study treatment to first randomization date of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	60
Median (95% Confidence Interval) [Months]	5.7	6.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Paclitaxel + Carboplatin, Bevacizumab + Paclitaxel + Carboplatin
	Comments	Differences in PFS between treatment arms was analyzed by 1-sided log rank test, stratified by gender and prior adjuvant therapy.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.639
	Comments	One-sided log-rank test at alpha = 0.20 significance level was used.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.093
	Confidence Interval	(2-Sided) 95%; 0.679 to 1.761
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Time in months from date of randomization to date of death due to any cause. OS was calculated as (the death date minus the first randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time Frame	Baseline, every 6 weeks until death or bimonthly after final study visit (up to 2.75 years)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	60
Median (95% Confidence Interval) [Months]	10.6	13.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Paclitaxel + Carboplatin, Bevacizumab + Paclitaxel + Carboplatin
	Comments	Differences in OS between treatment arms was analyzed by 1-sided log rank test, stratified by gender and prior adjuvant therapy.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.699
	Comments	One-sided log-rank test at alpha = 0.20 significance level was used.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.117
	Confidence Interval	(2-Sided) 95%; 0.739 to 1.689
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR: disappearance of all lesions (target and/or non target) and no appearance of new lesions. PR: at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, without progression of non target lesions and no appearance of new lesions.
Time Frame	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	60
Number (95% Confidence Interval) [Percentage of participants]	29.3 50.5%	43.3 72.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Paclitaxel + Carboplatin, Bevacizumab + Paclitaxel + Carboplatin
	Comments	P-value was calculated using 1-sided Cochran-Mantel-Haenszel test stratified by gender and prior adjuvant therapy. Risk ratio in comparison to the Bevacizumab group was calculated assuming all other factors as constant.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9422
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.676
	Confidence Interval	(2-Sided) 95%; 0.412 to 1.107
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years

Outcome Measure Data

Analysis Population Description

DR was calculated for the subgroup of participants from the ITT population, with a confirmed objective tumor response (CR or PR).

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	17	26
Median (95% Confidence Interval) [Months]	4.4	7.0

5. Secondary Outcome

Title	Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)
Description	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame	Pre-dose, 1 to 2 hours post-dose on Cycle 2 of Day 1 and Cycle 3 of Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhoea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Time Frame	Day (D) 1 of every cycle (C) then every 3 weeks until final study visit (up to 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population included participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or different drug from which they were randomized. 'n' signifies those participants evaluated for this measure at specific time point for each group respectively.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	60
Physical functioning (PF): Baseline (n=58, 59)	66.29 (22.04)	75.00 (22.21)
PF: C2 D1 (n=51, 53)	67.45 (23.48)	75.47 (20.24)
PF: C3 D1 (n=45, 47)	65.78 (24.40)	78.16 (18.43)
PF: C4 D1 (n=37, 48)	67.88 (20.01)	73.78 (19.14)
PF: C5 D1 (n=34, 38)	61.18 (24.09)	75.09 (16.38)
PF: C6 D1 (n=31, 33)	65.86 (19.17)	73.94 (18.66)
PF: C7 D1 (n=27, 30)	66.42 (22.15)	74.89 (18.67)
PF: C8 D1 (n=22, 28)	67.27 (22.44)	77.14 (18.98)
PF: C9 D1 (n=18, 23)	66.30 (27.77)	74.57 (19.02)
PF: C10 D1 (n=17, 20)	68.63 (25.36)	81.33 (14.92)
PF: C11 D1 (n=15, 19)	60.67 (23.58)	78.25 (16.00)
PF: C12 D1 (n=10, 17)	71.33 (20.86)	78.43 (19.65)
PF: C13 D1 (n=8, 14)	66.67 (25.94)	79.05 (21.22)
PF: End of treatment (EOT) (n=27, 38)	62.96 (21.11)	64.91 (24.83)
Role functioning: Baseline (n=58, 58)	60.92 (31.15)	60.63 (31.79)
Role functioning: C2 D1 (n=51, 53)	64.38 (31.98)	65.41 (29.02)
Role functioning: C3 D1 (n=45, 47)	58.15 (34.01)	70.92 (28.55)
Role functioning: C4 D1 (n=37, 48)	67.12 (26.49)	67.36 (25.02)
Role functioning: C5 D1 (n=34, 38)	57.35 (29.64)	66.23 (29.12)
Role functioning: C6 D1 (n=31, 33)	62.90 (30.34)	67.68 (29.15)
Role functioning: C7 D1 (n=28, 30)	55.36 (32.41)	63.89 (27.01)
Role functioning: C8 D1 (n=22, 28)	65.15 (29.05)	71.43 (19.70)
Role functioning: C9 D1 (n=18, 23)	63.89 (37.60)	70.29 (18.77)
Role functioning: C10 D1 (n=17, 20)	66.67 (28.87)	70.83 (20.14)
Role functioning: C11 D1 (n=15, 19)	60.00 (29.41)	71.93 (21.55)
Role functioning: C12 D1 (n=10, 17)	75.00 (21.15)	70.59 (21.67)
Role functioning: C13 D1 (n=8, 14)	62.50 (33.04)	80.95 (20.52)
Role functioning: EOT (n=27, 38)	57.41 (32.47)	57.90 (31.18)
Emotional functioning: Baseline (n=57, 57)	69.74 (23.45)	63.74 (27.44)
Emotional functioning: C2 D1 (n=50, 53)	78.33 (21.76)	73.64 (22.81)
Emotional functioning: C3 D1 (n=45, 48)	75.19 (21.36)	78.76 (20.69)
Emotional functioning: C4 D1 (n=37, 48)	75.75 (20.17)	76.04 (23.23)
Emotional functioning: C5 D1 (n=32, 38)	77.60 (18.38)	78.51 (21.37)
Emotional functioning: C6 D1 (n=29, 32)	78.74 (18.97)	77.35 (23.40)
Emotional functioning: C7 D1 (n=28, 30)	78.57 (22.62)	79.45 (20.50)
Emotional functioning: C8 D1 (n=22, 28)	77.65 (19.14)	81.25 (18.09)
Emotional functioning: C9 D1 (n=18, 23)	74.07 (19.78)	78.50 (23.39)
Emotional functioning: C10 D1 (n=17, 20)	77.94 (18.85)	78.33 (13.36)
Emotional functioning: C11 D1 (n=15, 19)	70.00 (21.32)	82.46 (18.61)
Emotional functioning: C12 D1 (n=10, 17)	74.17 (27.90)	77.45 (20.57)
Emotional functioning: C13 D1 (n=8, 14)	77.08 (22.60)	83.93 (14.79)
Emotional functioning: EOT (n=27, 38)	68.52 (26.39)	70.18 (25.60)
Cognitive Functioning: Baseline (n=57, 57)	80.12 (24.28)	83.33 (19.16)
Cognitive Functioning: C2 D1 (n=50, 53)	84.00 (20.47)	84.28 (21.29)
Cognitive Functioning: C3 D1 (n=45, 48)	85.19 (22.81)	85.42 (20.81)
Cognitive Functioning: C4 D1 (n=37, 48)	84.68 (18.99)	82.64 (20.03)
Cognitive Functioning: C5 D1 (n=32, 38)	84.37 (19.83)	83.33 (24.51)
Cognitive Functioning: C6 D1 (n=29, 32)	86.78 (18.03)	81.25 (21.06)
Cognitive Functioning: C7 D1 (n=28, 30)	79.76 (19.43)	85.56 (18.94)
Cognitive Functioning: C8 D1 (n=22, 28)	89.39 (17.48)	88.69 (17.00)
Cognitive Functioning: C9 D1 (n=18, 23)	84.26 (15.63)	86.23 (20.51)
Cognitive Functioning: C10 D1 (n=17, 20)	88.23 (12.86)	90.00 (13.68)
Cognitive Functioning: C11 D1 (n=15, 19)	82.22 (18.33)	85.96 (18.64)
Cognitive Functioning: C12 D1 (n=10, 17)	90.00 (14.05)	87.25 (20.01)
Cognitive Functioning: C13 D1 (n=8, 14)	85.42 (13.91)	95.24 (12.10)
Cognitive Functioning: EOT (n=27, 38)	77.78 (23.57)	78.95 (22.82)
Social functioning: Baseline (n=57, 57)	71.35 (27.59)	65.50 (32.25)
Social functioning: C2 D1 (n=50, 52)	69.67 (30.06)	75.32 (25.24)
Social functioning: C3 D1 (n=45, 48)	71.11 (27.62)	74.65 (24.79)
Social functioning: C4 D1 (n=37, 48)	73.42 (24.99)	71.53 (29.77)
Social functioning: C5 D1 (n=32, 38)	65.10 (26.22)	75.88 (27.04)
Social functioning: C6 D1 (n=29, 32)	70.11 (26.49)	71.88 (26.92)
Social functioning: C7 D1 (n=28, 30)	64.88 (32.50)	72.22 (23.71)
Social functioning: C8 D1 (n=22, 28)	71.97 (24.87)	72.02 (24.45)
Social functioning: C9 D1 (n=18, 23)	74.07 (29.83)	81.16 (16.13)
Social functioning: C10 D1 (n=17, 20)	72.55 (32.24)	79.17 (20.14)
Social functioning: C11 D1 (n=15, 19)	66.67 (28.17)	78.95 (16.52)
Social functioning: C12 D1 (n=10, 17)	71.67 (20.86)	80.39 (20.61)
Social functioning: C13 D1 (n=8, 14)	56.25 (28.08)	80.95 (18.32)
Social functioning: EOT (n=27, 38)	69.14 (26.03)	65.79 (26.83)
Fatigue: Baseline (n=57, 58)	40.45 (23.94)	38.89 (28.02)
Fatigue: C2 D1 (n=51, 53)	43.57 (21.98)	36.48 (25.26)
Fatigue: C3 D1 (n=45, 47)	47.41 (22.77)	33.80 (19.38)
Fatigue: C4 D1 (n=37, 48)	42.34 (19.22)	37.85 (19.40)
Fatigue: C5 D1 (n=34, 38)	44.61 (21.73)	36.84 (22.83)
Fatigue: C6 D1 (n=31, 33)	45.16 (23.65)	33.50 (21.45)
Fatigue: C7 D1 (n=28, 30)	47.82 (27.27)	40.74 (21.11)
Fatigue: C8 D1 (n=22, 28)	44.95 (24.84)	32.14 (20.14)
Fatigue: C9 D1 (n=18, 23)	40.12 (29.80)	28.98 (20.03)
Fatigue: C10 D1 (n=17, 20)	41.83 (25.62)	30.00 (19.78)
Fatigue: C11 D1 (n=15, 19)	47.78 (32.52)	28.07 (14.52)
Fatigue: C12 D1 (n=10, 17)	37.78 (19.74)	29.41 (18.82)
Fatigue: C13 D1 (n=8, 14)	50.00 (24.49)	26.19 (22.05)
Fatigue: EOT (n=27, 38)	51.03 (24.51)	43.13 (27.57)
Nausea and vomiting: Baseline (n=57, 59)	8.77 (17.85)	9.89 (21.91)
Nausea and vomiting: C2 D1 (n=51, 53)	7.19 (13.02)	5.35 (12.56)
Nausea and vomiting: C3 D1 (n=45, 47)	11.11 (17.77)	5.67 (11.67)
Nausea and vomiting: C4 D1 (n=37, 48)	10.81 (16.77)	7.29 (11.86)
Nausea and vomiting: C5 D1 (n=34, 38)	13.24 (21.63)	7.46 (14.34)
Nausea and vomiting: C6 D1 (n=31, 33)	13.44 (21.26)	10.61 (17.59)
Nausea and vomiting: C7 D1 (n=28, 30)	15.48 (22.65)	9.44 (14.31)
Nausea and vomiting: C8 D1 (n=22, 28)	14.40 (22.00)	5.95 (12.18)
Nausea and vomiting: C9 D1 (n=18, 23)	9.26 (13.06)	5.07 (20.98)
Nausea and vomiting: C10 D1 (n=17, 20)	11.77 (15.33)	8.33 (16.67)
Nausea and vomiting: C11 D1 (n=15, 19)	14.45 (17.67)	5.26 (9.71)
Nausea and vomiting: C12 D1 (n=10, 17)	15.00 (16.57)	6.68 (14.50)
Nausea and vomiting: C13 D1 (n=8, 14)	12.50 (17.25)	5.95 (14.03)
Nausea and vomiting: EOT (n=27, 38)	16.05 (22.40)	7.90 (14.36)
Pain: Baseline (n=57, 59)	31.29 (31.82)	35.31 (30.02)
Pain: C2 D1 (n=51, 53)	29.74 (29.87)	28.30 (29.16)
Pain: C3 D1 (n=45, 48)	30.00 (27.43)	18.75 (18.07)
Pain: C4 D1 (n=37, 48)	26.58 (18.62)	25.35 (27.29)
Pain: C5 D1 (n=34, 38)	25.00 (18.91)	24.12 (24.72)
Pain: C6 D1 (n=31, 33)	31.18 (18.63)	25.25 (28.90)
Pain: C7 D1 (n=28, 30)	28.57 (28.99)	27.22 (26.07)
Pain: C8 D1 (n=22, 28)	28.03 (25.91)	22.62 (23.66)
Pain: C9 D1 (n=18, 23)	33.33 (22.14)	27.54 (31.22)
Pain: C10 D1 (n=17, 20)	30.39 (26.51)	24.17 (24.47)
Pain: C11 D1 (n=15, 19)	43.33 (28.03)	18.42 (21.44)
Pain: C12 D1 (n=10, 17)	35.00 (21.45)	23.53 (29.50)
Pain: C13 D1 (n=8, 14)	35.42 (24.30)	16.67 (21.68)
Pain: EOT (n=27, 38)	38.27 (33.27)	34.65 (30.36)
Dyspnoea: Baseline (n=56, 58)	32.74 (30.15)	36.21 (33.21)
Dyspnoea: C2 D1 (n=51, 52)	32.03 (28.25)	24.36 (31.04)
Dyspnoea: C3 D1 (n=45, 47)	38.52 (28.39)	19.15 (23.82)
Dyspnoea: C4 D1 (n=37, 48)	33.33 (30.43)	21.53 (25.25)
Dyspnoea: C5 D1 (n=34, 38)	36.27 (33.20)	23.68 (27.84)
Dyspnoea: C6 D1 (n=31, 33)	36.56 (31.45)	20.20 (23.48)
Dyspnoea: C7 D1 (n=28, 30)	38.09 (31.05)	21.11 (20.50)
Dyspnoea: C8 D1 (n=22, 28)	27.27 (28.43)	16.67 (19.24)
Dyspnoea: C9 D1 (n=18, 23)	25.93 (33.44)	21.74 (21.58)
Dyspnoea: C10 D1 (n=17, 20)	27.45 (31.70)	18.33 (17.01)
Dyspnoea: C11 D1 (n=15, 19)	37.78 (33.01)	17.54 (23.22)
Dyspnoea: C12 D1 (n=10, 17)	23.33 (27.44)	21.57 (23.40)
Dyspnoea: C13 D1 (n=8, 14)	37.50 (37.53)	19.05 (17.12)
Dyspnoea: EOT (n=27, 38)	35.80 (27.62)	33.33 (33.78)
Insomnia: Baseline (n=57, 58)	46.20 (33.19)	37.93 (31.50)
Insomnia: C2 D1 (n=51, 53)	36.60 (36.06)	28.30 (33.59)
Insomnia: C3 D1 (n=45, 47)	30.37 (33.20)	29.08 (33.06)
Insomnia: C4 D1 (n=37, 48)	24.32 (26.81)	27.08 (28.89)
Insomnia: C5 D1 (n=34, 38)	28.43 (24.80)	23.68 (31.87)
Insomnia: C6 D1 (n=31, 33)	24.73 (25.77)	24.24 (29.19)
Insomnia: C7 D1 (n=28, 30)	23.81 (28.48)	25.55 (24.26)
Insomnia: C8 D1 (n=22, 28)	21.21 (26.32)	19.05 (23.00)
Insomnia: C9 D1 (n=18, 23)	25.93 (31.43)	23.19 (27.40)
Insomnia: C10 D1 (n=17, 20)	27.45 (26.97)	20.00 (25.13)
Insomnia: C11 D1 (n=15, 19)	33.33 (28.17)	22.81 (24.97)
Insomnia: C12 D1 (n=10, 17)	26.67 (21.08)	23.53 (28.30)
Insomnia: C13 D1 (n=8, 14)	12.50 (17.25)	16.67 (17.29)
Insomnia: EOT (n=27, 37)	28.39 (27.28)	36.94 (30.21)
Loss of appetite: Baseline (n=57, 59)	29.82 (28.65)	31.64 (34.14)
Loss of appetite: C2 D1 (n=51, 53)	23.53 (26.91)	20.75 (29.40)
Loss of appetite: C3 D1 (n=44, 47)	33.33 (32.94)	17.02 (25.89)
Loss of appetite: C4 D1 (n=37, 48)	26.13 (26.22)	23.61 (27.47)
Loss of appetite: C5 D1 (n=34, 38)	30.39 (33.20)	21.05 (29.43)
Loss of appetite: C6 D1 (n=31, 33)	27.96 (31.15)	23.23 (26.98)
Loss of appetite: C7 D1 (n=28, 30)	39.29 (34.01)	24.44 (23.05)
Loss of appetite: C8 D1 (n=22, 28)	36.36 (28.93)	19.05 (21.14)
Loss of appetite: C9 D1 (n=18, 23)	31.48 (26.75)	13.04 (24.08)
Loss of appetite: C10 D1 (n=17, 20)	39.22 (31.70)	20.00 (25.13)
Loss of appetite: C11 D1 (n=15, 19)	33.33 (35.64)	15.79 (17.10)
Loss of appetite: C12 D1 (n=10, 17)	16.67 (23.57)	23.53 (30.65)
Loss of appetite: C13 D1 (n=8, 14)	29.17 (21.36)	16.67 (28.49)
Loss of appetite: EOT (n=27, 38)	39.51 (34.64)	37.72 (33.93)
Constipation: Baseline (n=56, 57)	15.48 (23.75)	21.05 (31.89)
Constipation: C2 D1 (n=50, 53)	21.33 (28.38)	20.13 (26.43)
Constipation: C3 D1 (n=45, 47)	18.52 (24.16)	14.89 (23.88)
Constipation: C4 D1 (n=36, 48)	18.52 (26.96)	13.19 (21.46)
Constipation: C5 D1 (n=32, 38)	18.75 (22.30)	21.05 (27.31)
Constipation: C6 D1 (n=28, 33)	22.62 (25.75)	19.19 (28.90)
Constipation: C7 D1 (n=28, 30)	25.00 (26.64)	7.78 (14.34)
Constipation: C8 D1 (n=22, 28)	19.70 (19.68)	2.38 (8.74)
Constipation: C9 D1 (n=18, 23)	9.26 (19.15)	5.80 (12.92)
Constipation: C10 D1 (n=17, 20)	17.65 (20.81)	5.00 (12.21)
Constipation: C11 D1 (n=15, 19)	22.22 (20.57)	8.77 (18.73)
Constipation: C12 D1 (n=10, 17)	20.00 (23.31)	5.88 (17.62)
Constipation: C13 D1 (n=8, 14)	16.67 (25.20)	4.76 (12.10)
Constipation: EOT (n=27, 38)	20.99 (29.45)	14.03 (24.05)
Diarrhoea: Baseline (n=55, 57)	6.67 (17.45)	5.85 (14.26)
Diarrhoea: C2 D1 (n=50, 53)	11.33 (17.31)	10.06 (21.27)
Diarrhoea: C3 D1 (n=45, 48)	15.55 (18.26)	9.72 (21.70)
Diarrhoea: C4 D1 (n=37, 47)	13.51 (19.97)	5.67 (12.66)
Diarrhoea: C5 D1 (n=32, 38)	22.92 (32.17)	7.89 (18.07)
Diarrhoea: C6 D1 (n=29, 32)	21.84 (28.56)	10.42 (19.74)
Diarrhoea: C7 D1 (n=28, 30)	16.67 (26.45)	11.11 (15.98)
Diarrhoea: C8 D1 (n=22, 28)	24.24 (31.17)	4.76 (11.88)
Diarrhoea: C9 D1 (n=18, 23)	27.78 (28.58)	5.80 (12.92)
Diarrhoea: C10 D1 (n=17, 20)	23.53 (30.65)	10.00 (19.04)
Diarrhoea: C11 D1 (n=15, 19)	31.11 (34.43)	0.00 (0.00)
Diarrhoea: C12 D1 (n=10, 17)	43.33 (16.10)	0.00 (0.00)
Diarrhoea: C13 D1 (n=8, 14)	33.33 (25.20)	7.14 (14.19)
Diarrhoea: EOT (n=27, 38)	23.46 (28.96)	3.51 (12.94)
Financial difficulties: Baseline (n=56, 57)	22.62 (31.85)	21.64 (27.09)
Financial difficulties: C2 D1 (n=49, 53)	21.77 (31.59)	20.12 (27.22)
Financial difficulties: C3 D1 (n=45, 48)	25.93 (30.89)	18.05 (23.78)
Financial difficulties: C4 D1 (n=37, 48)	21.62 (27.46)	20.83 (30.46)
Financial difficulties: C5 D1 (n=32, 38)	26.04 (30.21)	21.05 (28.39)
Financial difficulties: C6 D1 (n=29, 32)	26.44 (28.70)	20.83 (29.02)
Financial difficulties: C7 D1 (n=28, 30)	26.19 (31.89)	26.67 (30.83)
Financial difficulties: C8 D1 (n=21, 28)	28.57 (35.41)	21.43 (32.98)
Financial difficulties: C9 D1 (n=18, 23)	27.78 (36.60)	17.39 (29.93)
Financial difficulties: C10 D1 (n=17, 19)	27.45 (33.82)	24.56 (33.04)
Financial difficulties: C11 D1 (n=15, 19)	20.00 (30.34)	19.30 (27.92)
Financial difficulties: C12 D1 (n=10, 17)	13.33 (23.31)	17.65 (26.66)
Financial difficulties: C13 D1 (n=8, 14)	20.83 (35.36)	16.67 (28.49)
Financial difficulties: EOT (n=27, 37)	23.46 (27.45)	28.83 (32.55)
Global health status/QoL: Baseline (n=57, 57)	53.22 (22.03)	54.97 (21.06)
Global health status/QoL: C2 D1 (n=49, 53)	58.16 (20.38)	59.59 (17.78)
Global health status/QoL: C3 D1 (n=45, 48)	56.67 (20.07)	59.72 (16.34)
Global health status/QoL: C4 D1 (n=37, 47)	57.21 (18.02)	57.80 (18.17)
Global health status/QoL: C5 D1 (n=32, 38)	58.07 (21.94)	61.84 (17.61)
Global health status/QoL: C6 D1 (n=29, 32)	53.45 (17.75)	60.94 (17.51)
Global health status/QoL: C7 D1 (n=28, 30)	55.65 (20.17)	58.61 (15.39)
Global health status/QoL: C8 D1 (n=22, 28)	56.82 (17.18)	60.71 (15.36)
Global health status/QoL: C9 D1 (n=18, 22)	56.48 (23.14)	64.40 (15.89)
Global health status/QoL: C10 D1 (n=17, 20)	55.39 (17.91)	62.50 (14.93)
Global health status/QoL: C11 D1 (n=15, 19)	47.78 (19.02)	63.60 (15.52)
Global health status/QoL: C12 D1 (n=10, 17)	54.17 (19.35)	63.73 (12.48)
Global health status/QoL: C13 D1 (n=8, 14)	53.13 (19.89)	58.33 (15.68)
Global health status/QoL: EOT (n=27, 38)	49.38 (20.92)	50.22 (21.62)

7. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score
Description	QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnoea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). 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.
Time Frame	Day 1 of every cycle then every 3 weeks until final study visit (up to 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population included participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or different drug from which they were randomized. 'n' signifies those participants evaluated for this measure at specific time point for each group respectively.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	60
Cough: Baseline (n=56, 59)	37.50 (31.18)	38.42 (24.62)
Cough: C2 D1 (n=50, 53)	30.67 (24.13)	30.19 (20.94)
Cough: C3 D1 (n=46, 47)	28.98 (25.92)	28.37 (23.03)
Cough: C4 D1 (n=37, 48)	29.73 (25.80)	27.08 (20.23)
Cough: C5 D1 (n=33, 38)	22.22 (18.00)	28.07 (23.92)
Cough: C6 D1 (n=29, 33)	26.44 (24.20)	26.26 (23.21)
Cough: C7 D1 (n=28, 29)	25.00 (21.52)	25.29 (24.65)
Cough: C8 D1 (n=22, 27)	21.21 (19.37)	19.75 (21.20)
Cough: C9 D1 (n=18, 23)	20.37 (20.26)	24.64 (25.06)
Cough: C10 D1 (n=17, 20)	23.53 (25.73)	21.67 (22.36)
Cough: C11 D1 (n=15, 19)	24.44 (23.46)	26.31 (23.78)
Cough: C12 D1 (n=10, 17)	26.66 (14.05)	29.41 (30.92)
Cough: C13 D1 (n=8, 14)	33.33 (25.20)	21.43 (21.11)
Cough: End of treatment (EOT) (n=26, 38)	33.33 (21.08)	33.33 (29.00)
Haemoptysis: Baseline (n=56, 59)	2.98 (11.51)	3.39 (10.16)
Haemoptysis: C2 D1 (n=50, 53)	2.67 (9.13)	1.89 (7.78)
Haemoptysis: C3 D1 (n=44, 47)	0.76 (5.02)	5.67 (14.44)
Haemoptysis: C4 D1 (n=36, 48)	0.93 (5.56)	3.47 (10.29)
Haemoptysis: C5 D1 (n=33, 38)	1.01 (5.80)	3.51 (12.94)
Haemoptysis: C6 D1 (n=29, 33)	3.45 (13.64)	3.03 (12.81)
Haemoptysis: C7 D1 (n=27, 29)	0.00 (0.00)	3.45 (10.33)
Haemoptysis: C8 D1 (n=22, 27)	0.00 (0.00)	1.23 (6.41)
Haemoptysis: C9 D1 (n=18, 23)	0.00 (0.00)	0.00 (0.00)
Haemoptysis: C10 D1 (n=17, 20)	0.00 (0.00)	0.00 (0.00)
Haemoptysis: C11 D1 (n=15, 19)	0.00 (0.00)	0.00 (0.00)
Haemoptysis: C12 D1 (n=10, 17)	0.00 (0.00)	0.00 (0.00)
Haemoptysis: C13 D1 (n=8, 14)	4.17 (11.78)	0.00 (0.00)
Haemoptysis: EOT (n=26, 38)	0.00 (0.00)	5.26 (16.49)
Dyspnoea: Baseline (n=56, 58)	29.17 (20.60)	31.42 (28.85)
Dyspnoea: C2 D1 (n=48, 53)	29.86 (25.23)	23.90 (21.51)
Dyspnoea: C3 D1 (n=45, 43)	33.83 (22.09)	20.41 (18.61)
Dyspnoea: C4 D1 (n=36, 45)	32.10 (20.01)	24.69 (21.57)
Dyspnoea: C5 D1 (n=33, 37)	30.30 (21.21)	23.12 (19.84)
Dyspnoea: C6 D1 (n=28, 31)	35.32 (24.76)	21.86 (18.70)
Dyspnoea: C7 D1 (n=27, 27)	30.45 (25.52)	20.16 (16.02)
Dyspnoea: C8 D1 (n=22, 26)	24.75 (21.94)	21.37 (16.61)
Dyspnoea: C9 D1 (n=18, 22)	27.78 (29.83)	18.69 (14.70)
Dyspnoea: C10 D1 (n=17, 19)	28.76 (27.80)	19.88 (15.08)
Dyspnoea: C11 D1 (n=15, 18)	27.41 (24.80)	19.75 (15.51)
Dyspnoea: C12 D1 (n=10, 17)	23.33 (22.50)	22.22 (19.25)
Dyspnoea: C13 D1 (n=8, 14)	37.50 (31.95)	16.67 (16.16)
Dyspnoea: EOT (n=25, 37)	34.22 (23.33)	33.63 (28.39)
Sore Mouth: Baseline (n=56, 58)	3.57 (12.19)	1.15 (6.13)
Sore Mouth: C2 D1 (n=51, 53)	18.95 (26.88)	9.43 (23.00)
Sore Mouth: C3 D1 (n=45, 47)	18.52 (28.03)	9.22 (21.65)
Sore Mouth: C4 D1 (n=37, 48)	21.62 (31.64)	8.33 (21.19)
Sore Mouth: C5 D1 (n=33, 38)	23.23 (36.79)	11.40 (23.60)
Sore Mouth: C6 D1 (n=28, 33)	16.67 (30.77)	6.06 (19.46)
Sore Mouth: C7 D1 (n=28, 29)	17.86 (27.94)	6.90 (16.38)
Sore Mouth: C8 D1 (n=22, 27)	16.67 (30.43)	3.70 (10.67)
Sore Mouth: C9 D1 (n=18, 23)	9.26 (15.36)	5.80 (16.37)
Sore Mouth: C10 D1 (n=17, 20)	19.61 (33.46)	10.00 (26.71)
Sore Mouth: C11 D1 (n=15, 19)	22.22 (37.09)	8.77 (24.45)
Sore Mouth: C12 D1 (n=10, 17)	16.67 (23.57)	7.84 (18.74)
Sore Mouth: C13 D1 (n=8, 14)	25.00 (38.83)	4.76 (12.10)
Sore Mouth: EOT (n=26, 38)	8.97 (24.14)	4.39 (13.80)
Dysphagia: Baseline (n=56, 59)	6.55 (17.31)	6.78 (14.88)
Dysphagia: C2 D1 (n=51, 53)	11.76 (22.92)	6.92 (17.73)
Dysphagia: C3 D1 (n=46, 47)	13.77 (20.58)	4.96 (11.99)
Dysphagia: C4 D1 (n=37, 48)	9.91 (20.59)	2.78 (9.31)
Dysphagia: C5 D1 (n=32, 38)	12.50 (26.44)	4.39 (11.42)
Dysphagia: C6 D1 (n=28, 33)	13.10 (27.73)	7.07 (16.15)
Dysphagia: C7 D1 (n=28, 28)	11.90 (26.00)	5.95 (15.85)
Dysphagia: C8 D1 (n=22, 27)	16.67 (26.73)	1.23 (6.41)
Dysphagia: C9 D1 (n=18, 23)	9.26 (15.36)	1.45 (6.95)
Dysphagia: C10 D1 (n=17, 20)	21.57 (26.20)	6.67 (17.44)
Dysphagia: C11 D1 (n=15, 19)	24.44 (29.46)	1.75 (7.65)
Dysphagia: C12 D1 (n=10, 17)	6.67 (14.05)	3.92 (16.17)
Dysphagia: C13 D1 (n=8, 14)	20.83 (24.80)	4.76 (17.82)
Dysphagia: EOT (n=26, 38)	7.69 (21.72)	7.89 (19.66)
Peripheral neuropathy: Baseline (n=56, 59)	9.52 (19.81)	15.25 (26.50)
Peripheral neuropathy: C2 D1 (n=51, 53)	24.84 (30.44)	33.96 (33.01)
Peripheral neuropathy: C3 D1 (n=46, 47)	37.68 (34.15)	34.75 (36.09)
Peripheral neuropathy: C4 D1 (n=37, 48)	45.05 (37.86)	38.19 (32.97)
Peripheral neuropathy: C5 D1 (n=33, 38)	50.51 (39.19)	42.11 (33.50)
Peripheral neuropathy: C6 D1 (n=29, 33)	55.17 (39.11)	52.53 (33.37)
Peripheral neuropathy: C7 D1 (n=28, 29)	48.81 (37.93)	54.02 (33.82)
Peripheral neuropathy: C8 D1 (n=22, 27)	57.58 (40.08)	50.62 (36.25)
Peripheral neuropathy: C9 D1 (n=17, 23)	45.10 (40.73)	56.52 (36.84)
Peripheral neuropathy: C10 D1 (n=17, 20)	45.10 (42.40)	48.33 (38.20)
Peripheral neuropathy: C11 D1 (n=14, 19)	50.00 (42.87)	49.12 (35.78)
Peripheral neuropathy: C12 D1 (n=9, 17)	55.56 (40.83)	54.90 (38.98)
Peripheral neuropathy: C13 D1 (n=8, 14)	58.33 (42.73)	47.62 (38.60)
Peripheral neuropathy: EOT (n=25, 38)	37.33 (35.12)	40.35 (38.87)
Alopecia: Baseline (n=56, 59)	2.98 (11.51)	2.26 (10.48)
Alopecia: C2 D1 (n=50, 53)	69.33 (33.56)	71.70 (32.29)
Alopecia: C3 D1 (n=46, 45)	73.91 (37.13)	68.89 (38.53)
Alopecia: C4 D1 (n=37, 45)	65.77 (40.43)	60.00 (42.40)
Alopecia: C5 D1 (n=33, 35)	61.62 (44.19)	64.76 (44.24)
Alopecia: C6 D1 (n=28, 32)	69.05 (42.48)	61.46 (45.68)
Alopecia: C7 D1 (n=28, 28)	39.29 (46.31)	40.48 (45.68)
Alopecia: C8 D1 (n=21, 27)	42.86 (44.90)	44.44 (48.92)
Alopecia: C9 D1 (n=18, 23)	27.78 (43.16)	31.88 (44.36)
Alopecia: C10 D1 (n=17, 20)	31.37 (43.25)	11.67 (29.17)
Alopecia: C11 D1 (n=14, 18)	16.67 (36.40)	16.67 (34.77)
Alopecia: C12 D1 (n=10, 17)	13.33 (28.11)	9.80 (28.30)
Alopecia: C13 D1 (n=8, 14)	8.33 (23.57)	7.14 (26.73)
Alopecia: EOT (n=26, 37)	33.33 (42.16)	27.03 (39.94)
Chest pain: Baseline (n=56, 59)	23.81 (28.93)	20.90 (25.45)
Chest pain: C2 D1 (n=51, 53)	18.95 (27.69)	10.06 (18.00)
Chest pain: C3 D1 (n=45, 47)	14.81 (25.18)	5.67 (12.66)
Chest pain: C4 D1 (n=36, 48)	14.81 (24.49)	9.03 (19.13)
Chest pain: C5 D1 (n=33, 38)	11.11 (19.84)	3.51 (10.37)
Chest pain: C6 D1 (n=28, 33)	15.48 (21.24)	1.01 (5.80)
Chest pain: C7 D1 (n=28, 28)	11.90 (18.62)	3.57 (10.50)
Chest pain: C8 D1 (n=22, 27)	13.64 (16.77)	3.70 (10.67)
Chest pain: C9 D1 (n=18, 23)	12.96 (20.26)	7.25 (14.06)
Chest pain: C10 D1 (n=17, 20)	13.72 (16.91)	8.33 (18.34)
Chest pain: C11 D1 (n=15, 19)	24.44 (29.46)	7.02 (13.96)
Chest pain: C12 D1 (n=10, 16)	13.33 (17.21)	2.08 (8.33)
Chest pain: C13 D1 (n=7, 14)	19.05 (26.23)	4.76 (12.10)
Chest pain: EOT (n=26, 37)	30.77 (33.89)	15.31 (24.34)
Arm/shoulder pain: Baseline (n=56, 59)	20.83 (27.39)	20.34 (29.04)
Arm/shoulder pain: C2 D1 (n=51, 53)	20.91 (28.25)	20.75 (24.66)
Arm/shoulder pain: C3 D1 (n=45, 47)	14.81 (25.18)	5.67 (12.66)
Arm/shoulder pain: C4 D1 (n=37, 47)	18.92 (25.51)	17.02 (30.19)
Arm/shoulder pain: C5 D1 (n=33, 38)	14.14 (26.39)	14.91 (26.51)
Arm/shoulder pain: C6 D1 (n=29, 33)	16.09 (26.16)	5.05 (12.14)
Arm/shoulder pain: C7 D1 (n=28, 29)	15.48 (23.10)	14.94 (22.86)
Arm/shoulder pain: C8 D1 (n=22, 26)	16.67 (26.73)	14.10 (19.26)
Arm/shoulder pain: C9 D1 (n=18, 23)	14.81 (23.49)	13.04 (19.43)
Arm/shoulder pain: C10 D1 (n=17, 20)	13.73 (23.74)	20.00 (27.36)
Arm/shoulder pain: C11 D1 (n=14, 19)	26.19 (29.75)	15.79 (23.22)
Arm/shoulder pain: C12 D1 (n=10, 17)	23.33 (22.50)	25.49 (32.34)
Arm/shoulder pain: C13 D1 (n=8, 14)	20.83 (24.80)	19.05 (25.20)
Arm/shoulder pain: EOT (n=26, 38)	21.80 (33.92)	23.68 (31.87)
Other pain: Baseline (n=52, 57)	28.85 (32.36)	25.15 (34.09)
Other pain: C2 D1 (n=49, 50)	26.53 (28.85)	32.67 (31.94)
Other pain: C3 D1 (n=46, 47)	34.06 (31.81)	23.40 (31.79)
Other pain: C4 D1 (n=36, 45)	25.93 (27.73)	28.15 (30.11)
Other pain: C5 D1 (n=32, 38)	25.00 (29.33)	26.32 (33.02)
Other pain: C6 D1 (n=28, 33)	29.76 (26.20)	27.27 (33.80)
Other pain: C7 D1 (n=28, 28)	32.14 (35.70)	35.71 (36.21)
Other pain: C8 D1 (n=22, 26)	16.67 (28.64)	25.64 (33.08)
Other pain: C9 D1 (n=15, 23)	31.11 (34.43)	31.88 (34.05)
Other pain: C10 D1 (n=16, 19)	25.00 (28.55)	22.81 (31.53)
Other pain: C11 D1 (n=14, 18)	42.86 (33.15)	25.93 (33.44)
Other pain: C12 D1 (n=10, 17)	33.33 (27.22)	27.45 (33.82)
Other pain: C13 D1 (n=8, 14)	29.17 (27.82)	26.19 (29.75)
Other pain: EOT (n=25, 37)	34.67 (32.60)	29.73 (36.67)
Medicine for pain: Baseline (n=37, 35)	60.36 (29.23)	66.67 (28.01)
Medicine for pain: C3 D1 (n=29, 24)	65.52 (31.48)	68.06 (31.82)
Medicine for pain: C4 D1 (n=19, 29)	63.16 (26.98)	72.41 (23.69)
Medicine for pain: C5 D1 (n=17, 22)	70.59 (26.04)	72.73 (22.15)
Medicine for pain: C6 D1 (n=16, 17)	66.67 (29.81)	72.55 (24.25)
Medicine for pain: C7 D1 (n=15, 14)	75.56 (26.63)	66.67 (29.24)
Medicine for pain: C8 D1 (n=13, 16)	66.67 (27.22)	75.00 (25.82)
Medicine for pain: C9 D1 (n=6, 14)	72.23 (13.61)	69.05 (20.52)
Medicine for pain: C10 D1 (n=10, 10)	73.34 (14.05)	60.00 (26.30)
Medicine for pain: C11 D1 (n=9, 9)	48.15 (17.57)	81.48 (17.57)
Medicine for pain: C12 D1 (n=6, 9)	55.56 (17.22)	70.37 (20.03)
Medicine for pain: C13 D1 (n=0, 0)	NA (NA)	NA (NA)
Medicine for pain: EOT (n=15, 19)	60.00 (22.54)	66.67 (29.40)
Medicine for pain: C2 D1 (n=30, 35)	62.22 (22.72)	71.43 (26.99)

8. Secondary Outcome

Title	Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile in Whole Blood
Description	RNA expression profiles of genes which were associated with tumor growth, angiogenesis and metastases were collected and correlated with efficacy.
Time Frame	Baseline, C1 D1, C1 D15, C2 D1, C3 D1, C4 D1 and C5 D1

Outcome Measure Data

Analysis Population Description

Data was not generated but sample was collected for banking and moved to a separate exploratory research database for future research.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	0	0

9. Secondary Outcome

Title	Circulating Endothelial Cells (CEC) in Blood: Total CEC
Description	Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs.
Time Frame	Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1

Outcome Measure Data

Analysis Population Description

ITT population: participants randomized with study drug designated according to initial randomization, regardless of whether participants received study drug or different drug. 'n': participants evaluated at specific time point for each group respectively. 'N' (Number of participants analyzed) signifies participants evaluable for the measure.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	59
Baseline (n=39, 37)	46815.38 (131531.755)	16960.41 (25527.526)
C1 D15 (n=27, 29)	11780.15 (13127.847)	21882.41 (67578.781)
C2 D1 (n=32, 28)	29229.09 (55724.997)	40507.36 (82161.060)
C3 D1 (n=24, 30)	19517.50 (19793.722)	25215.70 (42932.747)
C4 D1 (n=20, 27)	24556.05 (22434.011)	41944.59 (70239.938)
C5 D1 (n=18, 23)	28266.22 (39480.209)	37468.13 (82647.380)
C7 D1 (n=11, 14)	71770.91 (94182.032)	36964.36 (60577.084)
C9 D1 (n=7, 7)	58680.00 (78138.794)	107978.14 (206314.489)
C11 D1 (n=6, 6)	116620.83 (129577.280)	120847.67 (140674.394)

10. Secondary Outcome

Title	Circulating Endothelial Cells (CEC) in Blood
Description	Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs.
Time Frame	Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1

Outcome Measure Data

Analysis Population Description

ITT population: participants randomized with study drug designated according to initial randomization, regardless of whether participants received study drug or different drug. 'n': participants evaluated at specific time point for each group respectively. 'N' (Number of participants analyzed) signifies participants evaluable for the measure.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	58	59
Baseline (pVEGFR2+) (n=50, 42)	1936317.98 (1252665.900)	1764577.67 (1331540.549)
C1 D15 (pVEGFR2+) (n=38, 37)	1822095.74 (1678888.153)	1810049.32 (1330590.809)
C2 D1 (pVEGFR2+) (n=41, 35)	1767065.44 (1442193.213)	2090673.60 (1659128.892)
C3 D1 (pVEGFR2+) (n=33, 34)	1715569.39 (1515661.662)	1578940.53 (1274415.109)
C4 D1 (pVEGFR2+) (n=25, 32)	1472447.68 (970463.341)	1815402.16 (1263516.725)
C5 D1 (pVEGFR2+) (n=24, 26)	2208801.96 (3098289.400)	1794843.58 (1458412.725)
C7 D1 (pVEGFR2+) (n=16, 16)	1405048.00 (879770.893)	1634128.00 (1443612.089)
C9 D1 (pVEGFR2+) (n=12, 11)	2280989.75 (1050678.808)	2283985.00 (1093158.760)
C11 D1 (pVEGFR2+) (n=10, 9)	1828224.90 (1179020.490)	2354939.11 (1116283.011)
Baseline (VEGFR2+) (n=50, 42)	1694522.56 (1534520.504)	1841618.36 (1300088.201)
C1 D15 (VEGFR2+) (n=38, 37)	1634956.89 (1285333.248)	1740268.05 (1444881.394)
C2 D1 (VEGFR2+) (n=41, 35)	1597041.59 (865675.123)	1444404.94 (1097875.465)
C3 D1 (VEGFR2+) (n=33, 34)	1443986.61 (843071.909)	1504595.71 (1163469.112)
C4 D1 (VEGFR2+) (n=25, 32)	1181666.88 (673860.407)	1259913.44 (765707.741)
C5 D1 (VEGFR2+) (n=24, 25)	1371956.00 (948166.942)	1447188.88 (885864.695)
C7 D1 (VEGFR2+) (n=16, 16)	1028231.44 (495059.378)	1317560.13 (720095.027)
C9 D1 (VEGFR2+) (n=12, 11)	1485819.58 (953884.288)	1476621.00 (1688887.819)
C11 D1 (VEGFR2+) (n=10, 9)	1573298.80 (1152155.993)	1332064.78 (668964.428)
Baseline (pPDGFRB+) (n=50, 42)	1646702.34 (1482336.244)	1734853.24 (1485338.326)
C1 D15 (pPDGFRB+) (n=38, 37)	1253893.97 (894629.298)	1599671.65 (1669690.889)
C2 D1 (pPDGFRB+) (n=41, 35)	1395311.88 (1111766.454)	1885684.31 (1356916.305)
C3 D1 (pPDGFRB+) (n=33, 34)	1470448.94 (841336.398)	1285439.44 (1083860.541)
C4 D1 (pPDGFRB+) (n=25, 32)	1046445.72 (588769.375)	1514713.97 (1150805.007)
C5 D1 (pPDGFRB+) (n=24, 26)	2253114.67 (3314986.569)	2299459.38 (5140939.706)
C7 D1 (pPDGFRB+) (n=16, 16)	1380133.19 (1002147.826)	2163313.88 (3720352.717)
C9 D1 (pPDGFRB+) (n=12, 11)	2172539.75 (2323386.087)	2225289.18 (1126401.528)
C11 D1 (pPDGFRB+) (n=10, 9)	1580028.90 (927582.364)	3127640.22 (2817719.865)
Baseline (PDGFRB+) (n=50, 42)	1775826.12 (1485762.540)	3176459.69 (3222201.986)
C1 D15 (PDGFRB+) (n=38, 37)	1589914.37 (985828.939)	1819988.05 (1807664.991)
C2 D1 (PDGFRB+) (n=41, 35)	1840677.73 (1315688.806)	1586256.17 (1092406.544)
C3 D1 (PDGFRB+) (n=33, 34)	1690163.33 (1064816.034)	1518360.71 (1286285.813)
C4 D1 (PDGFRB+) (n=25, 32)	1288624.64 (641546.254)	1408366.91 (1013859.813)
C5 D1 (PDGFRB+) (n=24, 26)	1309639.50 (975890.557)	1364500.50 (1058758.211)
C7 D1 (PDGFRB+) (n=16, 16)	1049351.00 (587546.139)	1287039.25 (922009.811)
C9 D1 (PDGFRB+) (n=12, 11)	1666413.67 (1465165.325)	1625161.64 (1467355.491)
C11 D1 (PDGFRB+) (n=10, 9)	1533606.00 (1258733.501)	1959067.11 (1973194.943)

11. Secondary Outcome

Title	Plasma Concentration of Soluble Proteins
Description	Plasma concentrations of soluble proteins (soluble- stem-cell factor receptor (sKIT) vascular endothelial growth factor [VEGF], and vascular endothelial growth factor receptor-2 [VEGFR2], VEGFR3) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline.
Time Frame	Baseline, C1D1, C1D15, C2D1, C3D1, C4D1, C5D1, C7D1, C9D1 and C11D1

Outcome Measure Data

Analysis Population Description

ITT population: participants randomized with study drug designated according to initial randomization, regardless of whether participants received study drug or different drug. 'n': participants evaluated at specific time point for each group respectively. 'N' (Number of participants analyzed) signifies participants evaluable for the measure.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.	Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
Measure Participants	57	58
Baseline (SKIT) (n=52, 47)	49740.29 (16998.69)	49544.15 (14803.62)
C1 D15 (SKIT) (n=42, 36)	53095.48 (18233.85)	55801.39 (22058.63)
C2 D1 (SKIT) (n=41, 43)	52979.39 (18018.73)	55729.65 (21476.66)
C3 D1 (SKIT) (n=40, 38)	53817.75 (19638.72)	65634.14 (27097.91)
C4 D1 (SKIT) (n=32, 38)	56961.41 (20828.07)	72671.32 (33207.22)
C5 D1 (SKIT) (n=27, 34)	58305.00 (20311.85)	68677.21 (30073.83)
C7 D1 (SKIT) (n=18, 23)	50701.11 (17927.98)	75547.61 (24458.54)
C9 D1 (SKIT) (n=12, 16)	48680.42 (14791.32)	65990.78 (17003.08)
C11 D1 (SKIT) (n=11, 13)	49251.82 (19469.45)	66920.38 (12261.25)
Baseline (VEGF) (n=50, 48)	95.14 (66.60)	121.83 (141.22)
C1 D15 (VEGF) (n=40, 37)	117.08 (98.05)	287.19 (171.77)
C2 D1 (VEGF) (n=39, 43)	127.46 (128.06)	324.33 (153.65)
C3 D1 (VEGF) (n=39, 38)	148.06 (159.80)	368.23 (151.20)
C4 D1 (VEGF) (n=30, 38)	197.16 (282.49)	405.13 (173.86)
C5 D1 (VEGF) (n=25, 34)	184.77 (175.32)	400.16 (165.69)
C7 D1 (VEGF) (n=18, 23)	226.62 (202.53)	433.30 (172.14)
C9 D1 (VEGF) (n=12, 16)	273.17 (207.22)	422.38 (157.76)
C11 D1 (VEGF) (n=11, 13)	339.86 (303.71)	449.92 (144.50)
Baseline (VEGFR2) (n=52, 48)	9587.31 (1570.27)	9995.00 (2185.61)
C1 D15 (VEGFR2) (n=42, 37)	7828.10 (1959.39)	10781.35 (2311.90)
C2 D1 (VEGFR2) (n=41, 43)	7477.80 (2146.89)	10330.00 (2511.23)
C3 D1 (VEGFR2) (n=40, 38)	7058.50 (2037.12)	10129.47 (2244.65)
C4 D1 (VEGFR2) (n=32, 38)	6885.94 (1754.19)	9934.21 (1785.78)
C5 D1 (VEGFR2) (n=27, 34)	6565.93 (1755.75)	10140.59 (2056.40)
C7 D1 (VEGFR2) (n=18, 23)	6401.11 (2360.24)	10339.57 (1897.95)
C9 D1 (VEGFR2) (n=12, 16)	6291.67 (2235.24)	9421.25 (2446.42)
C11 D1 (VEGFR2) (n=11, 13)	5696.36 (2724.57)	9222.31 (2727.04)
Baseline (VEGFR3) (n=52, 48)	44390.77 (75118.17)	24718.33 (12494.07)
C1 D15 (VEGFR3) (n=42, 37)	33684.29 (52617.02)	17693.51 (9679.53)
C2 D1 (VEGFR3) (n=41, 43)	35780.49 (68287.68)	17798.37 (9710.23)
C3 D1 (VEGFR3) (n=40, 38)	34147.00 (74220.30)	15901.32 (8062.41)
C4 D1 (VEGFR3) (n=32, 38)	19730.94 (9237.69)	16307.37 (7409.61)
C5 D1 (VEGFR3) (n=27, 34)	17452.59 (8614.99)	16381.47 (6707.41)
C7 D1 (VEGFR3) (n=18, 23)	17896.67 (8360.82)	15626.30 (8873.31)
C9 D1 (VEGFR3) (n=12, 16)	21449.17 (12806.75)	14733.44 (6441.61)
C11 D1 (VEGFR3) (n=11, 13)	22332.73 (12408.37)	16048.46 (7064.47)

12. Other Pre-specified Outcome

Title	Plasma Concentration Change in the Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1) Genotype
Description	UGT1A1 an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.
Time Frame	Baseline (Day 1 of Cycle 1)

Outcome Measure Data

Analysis Population Description

Data was reported in listings but not summarized due to statistical constraints.

Arm/Group Title	Axitinib + Paclitaxel + Carboplatin	Bevacizumab+ Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive Axitinib (AG-013736) BID maintenance therapy.	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive Axitinib (AG-013736) BID maintenance therapy.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Axitinib + Paclitaxel + Carboplatin		Bevacizumab + Paclitaxel + Carboplatin
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet administered orally BID along with IV infusion of paclitaxel 200 mg per square meter (mg/m^2) over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive axitinib (AG-013736) BID maintenance therapy.		Bevacizumab 15 mg/kg infusion over 90 minutes every 3 weeks along with infusion of paclitaxel 200 mg/m^2 over 3 hours and carboplatin AUC of 6 mg*min/mL infusion over 30 minutes in cycles of 3 weeks. After completion or discontinuation of treatment for reasons other than disease progression, participants continued to receive bevacizumab maintenance therapy every 3 weeks.
All Cause Mortality
	Axitinib + Paclitaxel + Carboplatin		Bevacizumab + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Axitinib + Paclitaxel + Carboplatin		Bevacizumab + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/58 (53.4%)		19/59 (32.2%)
Blood and lymphatic system disorders
Anaemia	1/58 (1.7%)		0/59 (0%)
Febrile neutropenia	0/58 (0%)		1/59 (1.7%)
Leukopenia	1/58 (1.7%)		1/59 (1.7%)
Neutropenia	1/58 (1.7%)		2/59 (3.4%)
Pancytopenia	1/58 (1.7%)		0/59 (0%)
Thrombocytopenia	1/58 (1.7%)		1/59 (1.7%)
Cardiac disorders
Acute myocardial infarction	1/58 (1.7%)		0/59 (0%)
Atrial fibrillation	1/58 (1.7%)		1/59 (1.7%)
Cardiac arrest	1/58 (1.7%)		0/59 (0%)
Myocardial infarction	2/58 (3.4%)		0/59 (0%)
Pericardial effusion	1/58 (1.7%)		0/59 (0%)
Supraventricular tachycardia	1/58 (1.7%)		0/59 (0%)
Tachycardia	0/58 (0%)		1/59 (1.7%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion	1/58 (1.7%)		0/59 (0%)
Gastrointestinal disorders
Anal fissure	0/58 (0%)		1/59 (1.7%)
Diarrhoea	1/58 (1.7%)		0/59 (0%)
Oesophagitis	0/58 (0%)		2/59 (3.4%)
Vomiting	1/58 (1.7%)		1/59 (1.7%)
General disorders
Asthenia	3/58 (5.2%)		0/59 (0%)
Chest pain	0/58 (0%)		1/59 (1.7%)
Chills	0/58 (0%)		1/59 (1.7%)
Death	1/58 (1.7%)		0/59 (0%)
Disease progression	7/58 (12.1%)		3/59 (5.1%)
Fatigue	1/58 (1.7%)		2/59 (3.4%)
General physical health deterioration	0/58 (0%)		1/59 (1.7%)
Mucosal inflammation	1/58 (1.7%)		0/59 (0%)
Pain	1/58 (1.7%)		0/59 (0%)
Pyrexia	1/58 (1.7%)		0/59 (0%)
Immune system disorders
Anaphylactic reaction	1/58 (1.7%)		0/59 (0%)
Infections and infestations
Device related infection	1/58 (1.7%)		0/59 (0%)
Diverticulitis	1/58 (1.7%)		1/59 (1.7%)
Endocarditis bacterial	0/58 (0%)		1/59 (1.7%)
Lower respiratory tract infection	0/58 (0%)		2/59 (3.4%)
Neutropenic sepsis	1/58 (1.7%)		0/59 (0%)
Pneumonia	1/58 (1.7%)		1/59 (1.7%)
Sepsis	2/58 (3.4%)		0/59 (0%)
Staphylococcal infection	1/58 (1.7%)		0/59 (0%)
Urinary tract infection	1/58 (1.7%)		0/59 (0%)
Febrile infection	1/58 (1.7%)		0/59 (0%)
Investigations
Alanine aminotransferase increased	1/58 (1.7%)		0/59 (0%)
Aspartate aminotransferase increased	1/58 (1.7%)		0/59 (0%)
Blood alkaline phosphatase increased	1/58 (1.7%)		0/59 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/58 (0%)		1/59 (1.7%)
Dehydration	4/58 (6.9%)		0/59 (0%)
Hyperkalaemia	0/58 (0%)		1/59 (1.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/58 (0%)		1/59 (1.7%)
Myalgia	0/58 (0%)		1/59 (1.7%)
Nervous system disorders
Cerebral infarction	1/58 (1.7%)		0/59 (0%)
Headache	0/58 (0%)		1/59 (1.7%)
Loss of consciousness	0/58 (0%)		1/59 (1.7%)
Meningeal disorder	1/58 (1.7%)		0/59 (0%)
Psychiatric disorders
Anxiety	0/58 (0%)		1/59 (1.7%)
Confusional state	1/58 (1.7%)		1/59 (1.7%)
Hallucination	0/58 (0%)		1/59 (1.7%)
Mental status changes	1/58 (1.7%)		0/59 (0%)
Renal and urinary disorders
Renal failure acute	1/58 (1.7%)		1/59 (1.7%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/58 (0%)		1/59 (1.7%)
Dyspnoea	1/58 (1.7%)		1/59 (1.7%)
Haemoptysis	1/58 (1.7%)		1/59 (1.7%)
Pneumonia aspiration	1/58 (1.7%)		0/59 (0%)
Pneumothorax	1/58 (1.7%)		0/59 (0%)
Pulmonary embolism	1/58 (1.7%)		1/59 (1.7%)
Respiratory distress	1/58 (1.7%)		0/59 (0%)
Vascular disorders
Deep vein thrombosis	0/58 (0%)		1/59 (1.7%)
Hypertension	1/58 (1.7%)		0/59 (0%)
Hypotension	1/58 (1.7%)		0/59 (0%)
Peripheral ischaemia	0/58 (0%)		1/59 (1.7%)
Other (Not Including Serious) Adverse Events
	Axitinib + Paclitaxel + Carboplatin		Bevacizumab + Paclitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/58 (93.1%)		58/59 (98.3%)
Blood and lymphatic system disorders
Anaemia	12/58 (20.7%)		15/59 (25.4%)
Leukopenia	7/58 (12.1%)		5/59 (8.5%)
Neutropenia	18/58 (31%)		15/59 (25.4%)
Thrombocytopenia	12/58 (20.7%)		11/59 (18.6%)
Endocrine disorders
Hypothyroidism	9/58 (15.5%)		2/59 (3.4%)
Gastrointestinal disorders
Abdominal pain	6/58 (10.3%)		3/59 (5.1%)
Abdominal pain upper	3/58 (5.2%)		4/59 (6.8%)
Constipation	16/58 (27.6%)		17/59 (28.8%)
Diarrhoea	27/58 (46.6%)		20/59 (33.9%)
Dyspepsia	8/58 (13.8%)		2/59 (3.4%)
Nausea	21/58 (36.2%)		19/59 (32.2%)
Stomatitis	8/58 (13.8%)		6/59 (10.2%)
Vomiting	14/58 (24.1%)		11/59 (18.6%)
General disorders
Asthenia	17/58 (29.3%)		6/59 (10.2%)
Chest pain	8/58 (13.8%)		3/59 (5.1%)
Fatigue	20/58 (34.5%)		22/59 (37.3%)
Malaise	3/58 (5.2%)		0/59 (0%)
Mucosal inflammation	5/58 (8.6%)		3/59 (5.1%)
Pain	6/58 (10.3%)		6/59 (10.2%)
Pyrexia	6/58 (10.3%)		9/59 (15.3%)
Oedema peripheral	2/58 (3.4%)		6/59 (10.2%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/58 (0%)		3/59 (5.1%)
Infections and infestations
Lower respiratory tract infection	4/58 (6.9%)		6/59 (10.2%)
Urinary tract infection	4/58 (6.9%)		3/59 (5.1%)
Nasopharyngitis	0/58 (0%)		3/59 (5.1%)
Respiratory tract infection	2/58 (3.4%)		4/59 (6.8%)
Upper respiratory tract infection	0/58 (0%)		3/59 (5.1%)
Investigations
Weight decreased	10/58 (17.2%)		6/59 (10.2%)
Metabolism and nutrition disorders
Decreased appetite	25/58 (43.1%)		12/59 (20.3%)
Dehydration	3/58 (5.2%)		1/59 (1.7%)
Hypokalaemia	3/58 (5.2%)		3/59 (5.1%)
Hyponatraemia	4/58 (6.9%)		3/59 (5.1%)
Hyperglycaemia	2/58 (3.4%)		3/59 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	13/58 (22.4%)		11/59 (18.6%)
Back pain	10/58 (17.2%)		5/59 (8.5%)
Bone pain	5/58 (8.6%)		7/59 (11.9%)
Musculoskeletal chest pain	4/58 (6.9%)		1/59 (1.7%)
Musculoskeletal pain	3/58 (5.2%)		4/59 (6.8%)
Myalgia	7/58 (12.1%)		7/59 (11.9%)
Neck pain	4/58 (6.9%)		1/59 (1.7%)
Pain in extremity	4/58 (6.9%)		10/59 (16.9%)
Nervous system disorders
Dizziness	5/58 (8.6%)		4/59 (6.8%)
Dysgeusia	4/58 (6.9%)		6/59 (10.2%)
Headache	11/58 (19%)		4/59 (6.8%)
Lethargy	4/58 (6.9%)		5/59 (8.5%)
Neuropathy peripheral	15/58 (25.9%)		15/59 (25.4%)
Paraesthesia	6/58 (10.3%)		8/59 (13.6%)
Peripheral sensory neuropathy	3/58 (5.2%)		1/59 (1.7%)
Polyneuropathy	3/58 (5.2%)		2/59 (3.4%)
Syncope	3/58 (5.2%)		0/59 (0%)
Neurotoxicity	2/58 (3.4%)		5/59 (8.5%)
Psychiatric disorders
Anxiety	4/58 (6.9%)		4/59 (6.8%)
Depression	4/58 (6.9%)		0/59 (0%)
Insomnia	10/58 (17.2%)		8/59 (13.6%)
Renal and urinary disorders
Proteinuria	6/58 (10.3%)		6/59 (10.2%)
Respiratory, thoracic and mediastinal disorders
Cough	9/58 (15.5%)		9/59 (15.3%)
Dysphonia	7/58 (12.1%)		8/59 (13.6%)
Dyspnoea	17/58 (29.3%)		15/59 (25.4%)
Epistaxis	8/58 (13.8%)		10/59 (16.9%)
Haemoptysis	3/58 (5.2%)		6/59 (10.2%)
Oropharyngeal pain	3/58 (5.2%)		3/59 (5.1%)
Skin and subcutaneous tissue disorders
Alopecia	21/58 (36.2%)		27/59 (45.8%)
Palmar-plantar erythrodysaesthesia syndrome	3/58 (5.2%)		1/59 (1.7%)
Rash	6/58 (10.3%)		6/59 (10.2%)
Pruritus	2/58 (3.4%)		3/59 (5.1%)
Rash pruritic	0/58 (0%)		3/59 (5.1%)
Vascular disorders
Hypertension	24/58 (41.4%)		25/59 (42.4%)
Hypotension	6/58 (10.3%)		1/59 (1.7%)

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