Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine For Advanced Pancreatic Cancer.

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00471146
• Collaborator: (none)
• Enrollment: 630
• Locations: 205
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether investigational study drug, AG-013736, and gemcitabine are effective in the first-line treatment of advanced pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Pancreatic Ductal	Drug: AG-013736; Drug: Gemcitabine; Drug: Gemcitabine; Drug: placebo	Phase 3

Detailed Description

This study was prematurely discontinued for futility on 23 January 2009, based on a planned interim analysis by an independent Data Safety Monitoring Board (DSMB) that found no evidence of improvement in the primary endpoint (survival) in patients treated with axitinib and gemcitabine compared to gemcitabine alone. Enrollment on this study has been discontinued.

Study Design

• Study Type: Interventional
• Actual Enrollment: 630 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind Phase 3 Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine Plus Placebo For The First-Line Treatment Of Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer.
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: AG-013736; oral administration, starting dose 5 mg twice daily [BID] every day until unacceptable toxicity or tumor progression.; Drug: Gemcitabine; intravenous administration at 1,000 mg/m^2 day 1, day 8 and day 15 every 4 weeks (conventional dose) until unacceptable toxicity or tumor progression.
Active Comparator: B	Drug: Gemcitabine; intravenous administration at 1,000 mg/m^2 day 1, day 8 and day 15 every 4 weeks (conventional dose) until unacceptable toxicity or tumor progression.; Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Baseline until death or at least 1 year after the randomization of last participant]

   Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Baseline until disease progression or at least 1 year after the randomization of last participant]

   Time in weeks from randomization to the first documentation of objective tumor progression or death due to any cause. PFS was calculated as = (first event date minus randomization date plus 1) divided by 7. 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").

2. Percentage of Participants With Objective Response (OR) [Baseline, every 8 weeks until tumor progression or death]

   Percentage of participants with 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 was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

3. Duration of Response (DR) [Baseline until death or at least 1 year after the randomization of last participant]

   Time in weeks from the first documentation of objective tumor response 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 cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.

4. Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]

   EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, 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. Change from baseline=Cycle/Day score minus baseline score.

5. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]

   QLQ-PAN26 consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC). Questions include on altered bowel habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC. All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100; higher scores= greater degree of symptoms or treatment side effects and emotional issues.

6. Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]

   BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.

7. Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]

   EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

8. Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]

   EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.

9. Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736) [Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 23 months]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed, metastatic or locally-, advanced pancreatic adenocarcinoma not amenable to curative resection.

• Adequate renal, hepatic and bone marrow function.

• Performance status 0 or 1.

Exclusion Criteria:

• Prior treatment with any systemic chemotherapy for metastatic disease.

• Prior treatment with gemcitabine, AG-013736, or other vascular endothelial growth factor inhibitors.

• Current or recent bleeding, thromboembolic event and or use of a thrombolytic agent.

• Inability to take oral medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Antioch	California	United States	94531
2	Pfizer Investigational Site	Corona	California	United States	92878
3	Pfizer Investigational Site	Glendora	California	United States	91741
4	Pfizer Investigational Site	La Jolla	California	United States	92037
5	Pfizer Investigational Site	La Jolla	California	United States	92093
6	Pfizer Investigational Site	LaVerne	California	United States	91750
7	Pfizer Investigational Site	Pamona	California	United States	91105
8	Pfizer Investigational Site	Pasadena	California	United States	91105
9	Pfizer Investigational Site	Pleasent Hill	California	United States	94523
10	Pfizer Investigational Site	Pomona	California	United States	91767
11	Pfizer Investigational Site	Rancho Cucamonga	California	United States	91730
12	Pfizer Investigational Site	Rancho Mirage	California	United States	92270
13	Pfizer Investigational Site	Redlands	California	United States	92374
14	Pfizer Investigational Site	San Diego	California	United States	92103
15	Pfizer Investigational Site	San Diego	California	United States	92161
16	Pfizer Investigational Site	San Leandro	California	United States	94578
17	Pfizer Investigational Site	West Covina	California	United States	91790
18	Pfizer Investigational Site	Hollywood	Florida	United States	33021
19	Pfizer Investigational Site	Pembroke Pines	Florida	United States	33028
20	Pfizer Investigational Site	Stuart	Florida	United States	34994
21	Pfizer Investigational Site	Tampa	Florida	United States	33612
22	Pfizer Investigational Site	Atlanta	Georgia	United States	30309
23	Pfizer Investigational Site	Augusta	Georgia	United States	30901
24	Pfizer Investigational Site	Augusta	Georgia	United States	30909
25	Pfizer Investigational Site	Coeur D'Alene	Idaho	United States	83814
26	Pfizer Investigational Site	Alton	Illinois	United States	62002
27	Pfizer Investigational Site	Chicago	Illinois	United States	60637
28	Pfizer Investigational Site	Beech Grove	Indiana	United States	46107
29	Pfizer Investigational Site	Indianapolis	Indiana	United States	46237
30	Pfizer Investigational Site	Indianapolis	Indiana	United States	46260
31	Pfizer Investigational Site	Jeffersonville	Indiana	United States	47130
32	Pfizer Investigational Site	Louisville	Kentucky	United States	40202
33	Pfizer Investigational Site	Louisville	Kentucky	United States	40207
34	Pfizer Investigational Site	Louisville	Kentucky	United States	40217
35	Pfizer Investigational Site	Louisville	Kentucky	United States	40241
36	Pfizer Investigational Site	Shelbyville	Kentucky	United States	40065
37	Pfizer Investigational Site	Baton Rouge	Louisiana	United States	70806
38	Pfizer Investigational Site	Baton Rouge	Louisiana	United States	70809
39	Pfizer Investigational Site	Annapolis	Maryland	United States	21401
40	Pfizer Investigational Site	Burlington	Massachusetts	United States	01805
41	Pfizer Investigational Site	Peabody	Massachusetts	United States	01960
42	Pfizer Investigational Site	Kalamazoo	Michigan	United States	49007
43	Pfizer Investigational Site	Columbus	Mississippi	United States	39705
44	Pfizer Investigational Site	Corinth	Mississippi	United States	38834
45	Pfizer Investigational Site	Southaven	Mississippi	United States	38671
46	Pfizer Investigational Site	Tupelo	Mississippi	United States	38801
47	Pfizer Investigational Site	St. Louis	Missouri	United States	63136
48	Pfizer Investigational Site	Billings	Montana	United States	59101
49	Pfizer Investigational Site	Lincoln	Nebraska	United States	68510
50	Pfizer Investigational Site	Las Vegas	Nevada	United States	89135
51	Pfizer Investigational Site	Mineola	New York	United States	11501
52	Pfizer Investigational Site	Syracuse	New York	United States	13210
53	Pfizer Investigational Site	Canton	Ohio	United States	44718
54	Pfizer Investigational Site	Columbus	Ohio	United States	43214
55	Pfizer Investigational Site	Sylvania	Ohio	United States	43560
56	Pfizer Investigational Site	Portland	Oregon	United States	97227-1191
57	Pfizer Investigational Site	Knoxville	Tennessee	United States	37916
58	Pfizer Investigational Site	Knoxville	Tennessee	United States	37920
59	Pfizer Investigational Site	Knoxville	Tennessee	United States	37934
60	Pfizer Investigational Site	Memphis	Tennessee	United States	38104
61	Pfizer Investigational Site	Memphis	Tennessee	United States	38120
62	Pfizer Investigational Site	Austin	Texas	United States	78705
63	Pfizer Investigational Site	Austin	Texas	United States	78745
64	Pfizer Investigational Site	Austin	Texas	United States	78758
65	Pfizer Investigational Site	Austin	Texas	United States	78759
66	Pfizer Investigational Site	Dallas	Texas	United States	75325-7786
67	Pfizer Investigational Site	Dallas	Texas	United States	75325
68	Pfizer Investigational Site	Dallas	Texas	United States	75390
69	Pfizer Investigational Site	Round Rock	Texas	United States	78664
70	Pfizer Investigational Site	Salt Lake City	Utah	United States	84112
71	Pfizer Investigational Site	Lynchburg	Virginia	United States	24501
72	Pfizer Investigational Site	Everett	Washington	United States	98201
73	Pfizer Investigational Site	Federal Way	Washington	United States	98003
74	Pfizer Investigational Site	Kennewick	Washington	United States	99336
75	Pfizer Investigational Site	Lakewood	Washington	United States	98499
76	Pfizer Investigational Site	Puyallup	Washington	United States	98372
77	Pfizer Investigational Site	Tacoma	Washington	United States	98405
78	Pfizer Investigational Site	Bahia Blanca	Buenos Aires	Argentina	B8000FJI
79	Pfizer Investigational Site	La Plata	Buenos Aires	Argentina	B1900AVG
80	Pfizer Investigational Site	Ciudad Autonoma de Buenos Aires		Argentina	C1426ANZ
81	Pfizer Investigational Site	Santa Fe		Argentina	3000
82	Pfizer Investigational Site	St. Leonards	New South Wales	Australia	2065
83	Pfizer Investigational Site	Wollongong	New South Wales	Australia	2500
84	Pfizer Investigational Site	Clayton	Victoria	Australia	3168
85	Pfizer Investigational Site	East Bentleigh	Victoria	Australia	3165
86	Pfizer Investigational Site	Salzburg		Austria	A-5020
87	Pfizer Investigational Site	Wels		Austria	A-4600
88	Pfizer Investigational Site	Wien		Austria	1030
89	Pfizer Investigational Site	Wien		Austria	1090
90	Pfizer Investigational Site	Wien		Austria	A-1090
91	Pfizer Investigational Site	Brussel		Belgium	1090
92	Pfizer Investigational Site	Bruxelles		Belgium	1000
93	Pfizer Investigational Site	Bruxelles		Belgium	1200
94	Pfizer Investigational Site	Gent		Belgium	9000
95	Pfizer Investigational Site	Leuven		Belgium	3000
96	Pfizer Investigational Site	Wilrijk		Belgium	2610
97	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 1Z2
98	Pfizer Investigational Site	Kelowna	British Columbia	Canada	V1Y 5L3
99	Pfizer Investigational Site	Victoria	British Columbia	Canada	V8R 6V5
100	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R2H 2A6
101	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3E 0V9
102	Pfizer Investigational Site	Moncton	New Brunswick	Canada	E1C 6Z8
103	Pfizer Investigational Site	Kingston	Ontario	Canada	K7L 2V7
104	Pfizer Investigational Site	Kingston	Ontario	Canada	K7L 5P9
105	Pfizer Investigational Site	Oshawa	Ontario	Canada	L1G 2B9
106	Pfizer Investigational Site	Toronto	Ontario	Canada	M4N 3M5
107	Pfizer Investigational Site	Montreal	Quebec	Canada	H1T 2M4
108	Pfizer Investigational Site	Montreal	Quebec	Canada	H2X 3J4
109	Pfizer Investigational Site	Montreal	Quebec	Canada	H4J 1C5
110	Pfizer Investigational Site	Clichy cedex		France	92118
111	Pfizer Investigational Site	La Chaussee Saint Victor		France	41260
112	Pfizer Investigational Site	Marseille		France	13385 CEDEX 5
113	Pfizer Investigational Site	Montpellier Cedex 02		France	34298
114	Pfizer Investigational Site	PARIS Cedex 13		France	75651
115	Pfizer Investigational Site	Paris		France	75015
116	Pfizer Investigational Site	Pessac Cedex		France	33600
117	Pfizer Investigational Site	Rouen		France	76041
118	Pfizer Investigational Site	St Herblain Cedex		France	44805
119	Pfizer Investigational Site	Berlin		Germany	13353
120	Pfizer Investigational Site	Dresden		Germany	01307
121	Pfizer Investigational Site	Essen		Germany	45136
122	Pfizer Investigational Site	Greifswald		Germany	17475
123	Pfizer Investigational Site	Magdeburg		Germany	39130
124	Pfizer Investigational Site	Mannheim		Germany	68167
125	Pfizer Investigational Site	Muenchen		Germany	81377
126	Pfizer Investigational Site	Oldenburg		Germany	26133
127	Pfizer Investigational Site	Ulm		Germany	89081
128	Pfizer Investigational Site	Shatin	NT	Hong Kong
129	Pfizer Investigational Site	Budapest		Hungary	1097
130	Pfizer Investigational Site	Budapest		Hungary	1106
131	Pfizer Investigational Site	Budapest		Hungary	1122
132	Pfizer Investigational Site	Kaposvar		Hungary	7400
133	Pfizer Investigational Site	Szentes		Hungary	6600
134	Pfizer Investigational Site	Zalaegerszeg		Hungary	8900
135	Pfizer Investigational Site	Ahmedabad	Gujarat	India	380 009
136	Pfizer Investigational Site	Bangalore	Karnataka	India	560 078
137	Pfizer Investigational Site	Cochin	Kerala	India	682 304
138	Pfizer Investigational Site	Andhra	Pradesh	India	500 034
139	Pfizer Investigational Site	Chennai	Tamil Nadu	India	600035
140	Pfizer Investigational Site	Dublin 24		Ireland
141	Pfizer Investigational Site	Dublin		Ireland	4
142	Pfizer Investigational Site	Bologna		Italy	40138
143	Pfizer Investigational Site	Catania		Italy	95122
144	Pfizer Investigational Site	Milano		Italy	20132
145	Pfizer Investigational Site	Milano		Italy	20133
146	Pfizer Investigational Site	Padova		Italy	35128
147	Pfizer Investigational Site	Verona		Italy	37134
148	Pfizer Investigational Site	Nagoya	Aichi	Japan
149	Pfizer Investigational Site	Chiba-shi	Chiba-ken	Japan
150	Pfizer Investigational Site	Chiba city	Chiba	Japan
151	Pfizer Investigational Site	Kashiwa-shi	Chiba	Japan
152	Pfizer Investigational Site	Fukuoka-shi	Fukuoka-ken	Japan
153	Pfizer Investigational Site	Yokohama-shi	Kanagawa	Japan
154	Pfizer Investigational Site	Osaka-shi	Osaka-fu	Japan
155	Pfizer Investigational Site	Suntougun	Shizuoka	Japan
156	Pfizer Investigational Site	Chuo-ku	Tokyo	Japan
157	Pfizer Investigational Site	Seoul		Korea, Republic of	110-744
158	Pfizer Investigational Site	Seoul		Korea, Republic of	135-710
159	Pfizer Investigational Site	Seoul		Korea, Republic of	136-705
160	Pfizer Investigational Site	Seoul		Korea, Republic of	138-736
161	Pfizer Investigational Site	Amsterdam	Noord Holland	Netherlands	1105 AZ
162	Pfizer Investigational Site	Amsterdam		Netherlands	1081 HV
163	Pfizer Investigational Site	Moscow		Russian Federation	115478
164	Pfizer Investigational Site	Moscow		Russian Federation	125376
165	Pfizer Investigational Site	Moscow		Russian Federation	129128
166	Pfizer Investigational Site	Omsk		Russian Federation	644013
167	Pfizer Investigational Site	Sochi		Russian Federation	354057
168	Pfizer Investigational Site	St. Petersburg		Russian Federation	191104
169	Pfizer Investigational Site	St. Petersburg		Russian Federation	198255
170	Pfizer Investigational Site	Singapore		Singapore	119074
171	Pfizer Investigational Site	Singapore		Singapore	16910
172	Pfizer Investigational Site	Cape Town		South Africa	7500
173	Pfizer Investigational Site	Observatory		South Africa	7925
174	Pfizer Investigational Site	Parktown		South Africa	2193
175	Pfizer Investigational Site	Port Elizabeth		South Africa	6001
176	Pfizer Investigational Site	Pretoria		South Africa	0181
177	Pfizer Investigational Site	Sandton		South Africa	2199
178	Pfizer Investigational Site	Palma de Mallorca	Islas Baleares	Spain	07198
179	Pfizer Investigational Site	Mostoles	Madrid	Spain	28935
180	Pfizer Investigational Site	Pamplona	Navarra	Spain	31008
181	Pfizer Investigational Site	Barcelona		Spain	08035
182	Pfizer Investigational Site	Barcelona		Spain	08036
183	Pfizer Investigational Site	Las Palmas de Gran Canaria		Spain	35020
184	Pfizer Investigational Site	Madrid		Spain	28046
185	Pfizer Investigational Site	Malaga		Spain	29010
186	Pfizer Investigational Site	Santa Cruz de Tenerife		Spain	38320
187	Pfizer Investigational Site	Toledo		Spain	45004
188	Pfizer Investigational Site	Lund		Sweden	221 85
189	Pfizer Investigational Site	Uppsala		Sweden	751 85
190	Pfizer Investigational Site	Winterthur		Switzerland	8401
191	Pfizer Investigational Site	Kuei-Shan Jsoamg	Taoyuan County	Taiwan	333
192	Pfizer Investigational Site	Taichung		Taiwan	404
193	Pfizer Investigational Site	Taipei		Taiwan	112
194	Pfizer Investigational Site	Whitchurch	Cardiff	United Kingdom	CF14 2TL
195	Pfizer Investigational Site	Maidstone	Kent	United Kingdom	ME16 9QQ
196	Pfizer Investigational Site	Leicester	Leicestershire	United Kingdom	LE1 5WW
197	Pfizer Investigational Site	Withington	Manchester	United Kingdom	M20 4BX
198	Pfizer Investigational Site	Northwood	Middlesex	United Kingdom	HA6 2RN
199	Pfizer Investigational Site	Birmingham		United Kingdom	B15 2TA
200	Pfizer Investigational Site	Birmingham		United Kingdom	B15 2TT
201	Pfizer Investigational Site	Edinburgh		United Kingdom	EH4 2XU
202	Pfizer Investigational Site	London		United Kingdom	EC1A 7BE
203	Pfizer Investigational Site	London		United Kingdom	W12 OHS
204	Pfizer Investigational Site	Manchester		United Kingdom	M20 4BX
205	Pfizer Investigational Site	Southhampton		United Kingdom	S016 6YD

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: NCT00471146
• Other Study ID Numbers: A4061028
• First Posted: May 9, 2007
• Last Update Posted: Jul 16, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Pfizer: Randomized Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine Plus Placebo For Advanced Pancreatic Cancer.
• Additional relevant MeSH terms: Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Gemcitabine; Axitinib

Study Results

Participant Flow

Arm/Group Title	Axitinib + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) in cycles of 4 weeks. Gemcitabine 1000 mg per square meter (mg/m^2) 30 minutes intravenous (IV) infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Period Title: Overall Study
STARTED	314	316
Treated	305	308
COMPLETED	142	142
NOT COMPLETED	172	174

Baseline Characteristics

Arm/Group Title	Axitinib + Gemcitabine	Placebo + Gemcitabine	Total
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Total of all reporting groups
Overall Participants	314	316	630
Age, Customized (Number) [Number]
Less than 65 years	203 64.6%	179 56.6%	382 60.6%
Greater than or equal to 65 years	111 35.4%	137 43.4%	248 39.4%
Sex: Female, Male (Count of Participants)
Female	123 39.2%	128 40.5%	251 39.8%
Male	191 60.8%	188 59.5%	379 60.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. 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 until death or at least 1 year after the randomization of last participant

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Median (95% Confidence Interval) [Weeks]	36.9	35.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Gemcitabine, Placebo + Gemcitabine
	Comments	Differences in OS between treatment arms was analyzed by 1-sided log rank test, stratified for extent of disease (locally advanced cancer versus metastatic cancer).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5436
	Comments	One-sided log-rank test at alpha = 0.025 significance level was used.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.014
	Confidence Interval	(2-Sided) 95%; 0.786 to 1.309
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Time in weeks from randomization to the first documentation of objective tumor progression or death due to any cause. PFS was calculated as = (first event date minus randomization date plus 1) divided by 7. 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 until disease progression or at least 1 year after the randomization of last participant

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Median (95% Confidence Interval) [Weeks]	19.1	18.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Gemcitabine, Placebo + Gemcitabine
	Comments	Differences in PFS between treatment arms was analyzed by 1-sided log rank test, stratified for extent of disease (locally advanced cancer versus metastatic cancer).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5203
	Comments	One-sided log-rank test at alpha = 0.025 significance level was used.The p-value was not adjusted for multiple testing.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.006
	Confidence Interval	(2-Sided) 95%; 0.779 to 1.298
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with 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 was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.
Time Frame	Baseline, every 8 weeks until tumor progression or death

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Number (95% Confidence Interval) [Percentage of participants]	4.9 1.6%	1.6 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Gemcitabine, Placebo + Gemcitabine
	Comments	Differences in OR between treatment arms was analyzed by 1-sided Cochran-Mantel-Haenszel (CMH) test, stratified for extent of disease (locally advanced cancer versus metastatic cancer).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; 1.0 to 10.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in weeks from the first documentation of objective tumor response 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 cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.
Time Frame	Baseline until death or at least 1 year after the randomization of last participant

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	12	4
Median (95% Confidence Interval) [Weeks]	33.1	NA

5. Secondary Outcome

Title	Change From Baseline in 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 (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, 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. Change from baseline=Cycle/Day score minus baseline score.
Time Frame	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Physical functioning: Baseline (n=295, 289)	77.445 (20.3052)	78.546 (18.9192)
Physical functioning: Change at C2 D1 (n=233, 233)	-2.713 (16.7682)	-3.261 (15.0742)
Physical functioning: Change at C3 D1 (n=173, 179)	-5.897 (19.3522)	-1.565 (16.2738)
Physical functioning: Change at C4 D1 (n=134, 133)	-5.671 (18.8623)	-1.453 (17.1209)
Physical functioning: Change at C5 D1 (n=96, 82)	-2.498 (21.8687)	-0.076 (16.9709)
Physical functioning: Change at C6 D1 (n=59, 58)	-5.193 (19.6995)	-1.719 (15.5260)
Physical functioning: Change at C7 D1 (n=38, 37)	-1.924 (14.2726)	0.011 (18.9261)
Physical functioning: Change at C8 D1 (n=15, 21)	-4.000 (16.8759)	0.014 (13.8428)
Physical functioning: Change at C9 D1 (n=9, 9)	0.033 (15.2534)	-12.578 (20.9490)
Physical functioning: Change at C10 D1 (n=3, 4)	6.667 (17.5754)	-1.675 (22.0563)
Physical functioning: Change at C11 D1 (n=1, 1)	0.000 (NA)	-6.600 (NA)
Physical functioning: Change at C12 D1 (n=1, 0)	0.000 (NA)	NA (NA)
Physical functioning: Change at C13 D1 (n=1, 0)	0.000 (NA)	NA (NA)
Physical functioning:Change at followup (n=67, 70)	-17.713 (23.8263)	-11.523 (21.0513)
Role functioning: Baseline (n=297, 295)	66.3 (30.09)	68.1 (30.72)
Role functioning: Change at C2 D1 (n=239, 242)	-2.2 (30.95)	-2.8 (25.75)
Role functioning: Change at C3 D1 (n=177, 185)	-4.6 (32.65)	1.5 (26.90)
Role functioning: Change at C4 D1 (n=135, 136)	-4.3 (32.13)	1.2 (27.18)
Role functioning: Change at C5 D1 (n=99, 81)	-0.5 (34.95)	-2.7 (29.63)
Role functioning: Change at C6 D1 (n=60, 58)	-4.4 (29.25)	-2.3 (24.27)
Role functioning: Change at C7 D1 (n=38, 37)	-3.1 (25.07)	-1.3 (26.75)
Role functioning: Change at C8 D1 (n=16, 21)	-6.2 (20.05)	0.0 (31.63)
Role functioning: Change at C9 D1 (n=9, 9)	1.9 (28.21)	-20.4 (33.11)
Role functioning: Change at C10 D1 (n=3, 4)	5.6 (9.64)	-4.2 (28.46)
Role functioning: Change at C11 D1 (n=1, 1)	0.0 (NA)	-50.0 (NA)
Role functioning: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Role functioning: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Role functioning: Change at follow-up (n=66, 72)	-20.0 (31.52)	-14.1 (32.34)
Emotional functioning (EF): Baseline (n=294, 287)	70.8 (22.01)	71.7 (22.47)
EF: Change at C2 D1 (n=233, 229)	5.0 (21.48)	5.0 (18.92)
EF: Change at C3 D1 (n=170, 180)	3.7 (20.19)	3.4 (18.95)
EF: Change at C4 D1 (n=134, 131)	3.0 (22.54)	5.2 (21.12)
EF: Change at C5 D1 (n=96, 80)	4.3 (21.09)	5.9 (17.24)
EF: Change at C6 D1 (n=60, 56)	4.0 (19.31)	6.7 (17.43)
EF: Change at C7 D1 (n=37, 34)	0.0 (18.84)	3.2 (16.28)
EF: Change at C8 D1 (n=17, 19)	-2.9 (22.05)	5.3 (14.74)
EF: Change at C9 D1 (n=9, 9)	3.7 (16.72)	-4.6 (15.07)
EF: Change at C10 D1 (n=3, 4)	13.9 (12.73)	2.1 (18.50)
EF: Change at C11 D1 (n=1, 1)	0.0 (NA)	-16.6 (NA)
EF: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
EF: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
EF: Change at follow-up (n=65, 71)	-7.3 (23.51)	-2.7 (23.14)
Cognitive Functioning (CF): Baseline (n=293, 288)	78.7 (22.26)	80.9 (21.50)
CF: Change at C2 D1 (n=234, 234)	-1.1 (19.86)	-0.3 (17.74)
CF: Change at C3 D1 (n=172, 179)	-2.1 (20.43)	-0.9 (18.67)
CF: Change at C4 D1 (n=134, 134)	-4.2 (19.98)	2.0 (18.62)
CF: Change at C5 D1 (n=97, 80)	-1.4 (20.21)	1.7 (18.86)
CF: Change at C6 D1 (n=60, 56)	-3.1 (19.27)	-4.5 (19.97)
CF: Change at C7 D1 (n=38, 34)	-4.4 (18.45)	0.5 (14.50)
CF: Change at C8 D1 (n=17, 17)	-8.8 (22.15)	-2.9 (23.74)
CF: Change at C9 D1 (n=9, 9)	-0.0 (25.03)	-1.8 (24.22)
CF: Change at C10 D1 (n=3, 4)	-5.6 (9.64)	8.3 (28.88)
CF: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
CF: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
CF: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
CF: Change at follow-up (n=65, 71)	-12.6 (25.01)	-7.5 (25.47)
Social functioning: Baseline (n=289, 286)	68.9 (27.98)	69.7 (28.83)
Social functioning: Change at C2 D1 (n=232, 230)	1.3 (24.73)	0.9 (26.35)
Social functioning: Change at C3 D1 (n=169, 178)	-1.3 (29.38)	3.2 (27.31)
Social functioning: Change at C4 D1 (n=132, 134)	0.1 (25.51)	0.6 (26.83)
Social functioning: Change at C5 D1 (n=95, 80)	2.1 (27.31)	0.8 (27.93)
Social functioning: Change at C6 D1 (n=58, 56)	-4.9 (28.79)	1.5 (29.52)
Social functioning: Change at C7 D1 (n=37, 35)	-5.4 (20.05)	2.4 (29.47)
Social functioning: Change at C8 D1 (n=17, 19)	4.9 (29.91)	-1.7 (27.72)
Social functioning: Change at C9 D1 (n=9, 9)	-0.0 (32.29)	-1.8 (28.20)
Social functioning: Change at C10 D1 (n=3, 4)	5.6 (9.64)	12.5 (43.83)
Social functioning: Change at C11 D1 (n=1, 1)	0.0 (NA)	33.4 (NA)
Social functioning: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Social functioning: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Social functioning: Change at follow-up (n=64, 70)	-13.3 (33.75)	-2.6 (33.88)
Fatigue: Baseline (n=293, 289)	41.0 (23.87)	40.1 (25.12)
Fatigue: Change at C2 D1 (n=227, 228)	2.8 (21.15)	2.1 (20.12)
Fatigue: Change at C3 D1 (n=170, 181)	3.4 (21.94)	-0.9 (21.76)
Fatigue: Change at C4 D1 (n=132, 132)	5.6 (23.97)	-1.1 (22.77)
Fatigue: Change at C5 D1 (n=97, 80)	-0.0 (24.39)	1.1 (21.92)
Fatigue: Change at C6 D1 (n=60, 57)	5.0 (21.31)	0.0 (21.22)
Fatigue: Change at C7 D1 (n=38, 36)	1.8 (20.61)	2.2 (19.12)
Fatigue: Change at C8 D1 (n=17, 20)	7.2 (22.89)	4.4 (22.05)
Fatigue: Change at C9 D1 (n=9, 9)	-6.2 (21.63)	14.8 (24.21)
Fatigue: Change at C10 D1 (n=3, 4)	-11.1 (19.28)	-5.5 (27.98)
Fatigue: Change at C11 D1 (n=1, 1)	0.0 (NA)	11.1 (NA)
Fatigue: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Fatigue: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Fatigue: Change at follow-up (n=63, 71)	13.1 (25.93)	12.1 (25.95)
Nausea and vomiting: Baseline (n=295, 294)	12.9 (19.19)	13.1 (19.75)
Nausea and vomiting: Change at C2 D1 (n=238, 239)	3.7 (20.69)	2.9 (22.93)
Nausea and vomiting: Change at C3 D1 (n=176, 185)	1.9 (20.38)	-0.4 (19.54)
Nausea and vomiting: Change at C4 D1 (n=133, 135)	3.5 (20.82)	0.4 (19.68)
Nausea and vomiting: Change at C5 D1 (n=98, 81)	4.6 (22.16)	1.0 (18.88)
Nausea and vomiting: Change at C6 D1 (n=60, 59)	6.9 (22.61)	2.8 (20.33)
Nausea and vomiting: Change at C7 D1 (n=38, 37)	1.3 (19.52)	2.7 (20.24)
Nausea and vomiting: Change at C8 D1 (n=17, 21)	-4.9 (18.41)	0.8 (22.66)
Nausea and vomiting: Change at C9 D1 (n=9, 9)	-13.0 (32.02)	-5.6 (18.64)
Nausea and vomiting: Change at C10 D1 (n=3, 4)	-11.1 (19.23)	8.3 (9.58)
Nausea and vomiting: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Nausea and vomiting: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Nausea and vomiting: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Nausea and vomiting: Change at followup (n=68, 73)	9.8 (25.63)	7.5 (22.40)
Pain: Baseline (n=291, 291)	40.7 (30.16)	36.9 (29.57)
Pain: Change at C2 D1 (n=231, 234)	-10.1 (29.47)	-7.9 (25.28)
Pain: Change at C3 D1 (n=169, 181)	-13.6 (29.81)	-11.2 (26.63)
Pain: Change at C4 D1 (n=131, 135)	-12.2 (32.48)	-7.8 (27.14)
Pain: Change at C5 D1 (n=97, 80)	-10.5 (32.75)	-6.9 (26.21)
Pain: Change at C6 D1 (n=59, 58)	-11.9 (27.51)	-7.5 (29.48)
Pain: Change at C7 D1 (n=38, 35)	-14.0 (27.81)	-9.5 (24.67)
Pain: Change at C8 D1 (n=17, 20)	-9.8 (26.39)	-6.7 (29.32)
Pain: Change at C9 D1 (n=9, 9)	-22.2 (43.29)	-5.6 (39.08)
Pain: Change at C10 D1 (n=3, 4)	-33.3 (33.30)	-4.2 (45.88)
Pain: Change at C11 D1 (n=1, 1)	0.0 (NA)	-33.3 (NA)
Pain: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pain: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pain: Change at follow-up (n=66, 72)	3.3 (37.01)	3.5 (31.14)
Dyspnoea: Baseline (n=295, 295)	16.1 (22.30)	14.8 (23.55)
Dyspnoea: Change at C2 D1 (n=238, 240)	5.5 (23.58)	2.1 (20.91)
Dyspnoea: Change at C3 D1 (n=175, 186)	5.7 (26.84)	3.9 (24.67)
Dyspnoea: Change at C4 D1 (n=135, 135)	7.7 (26.99)	4.4 (21.08)
Dyspnoea: Change at C5 D1 (n=98, 82)	4.4 (26.05)	2.8 (18.29)
Dyspnoea: Change at C6 D1 (n=60, 59)	9.4 (26.09)	-0.0 (16.37)
Dyspnoea: Change at C7 D1 (n=37, 37)	6.3 (24.63)	5.4 (20.05)
Dyspnoea: Change at C8 D1 (n=16, 21)	4.2 (20.62)	12.7 (24.66)
Dyspnoea: Change at C9 D1 (n=9, 9)	11.1 (47.14)	14.8 (29.39)
Dyspnoea: Change at C10 D1 (n=3, 4)	-11.1 (50.92)	0.0 (27.19)
Dyspnoea: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Dyspnoea: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Dyspnoea: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Dyspnoea: Change at follow-up (n=68, 73)	13.2 (28.30)	8.7 (24.23)
Insomnia: Baseline (n=297, 295)	36.8 (31.95)	32.2 (32.17)
Insomnia: Change at C2 D1 (n=240, 241)	-13.6 (33.55)	-7.3 (33.16)
Insomnia: Change at C3 D1 (n=178, 185)	-13.5 (33.33)	-8.7 (33.30)
Insomnia: Change at C4 D1 (n=134, 134)	-12.7 (38.52)	-11.2 (27.41)
Insomnia: Change at C5 D1 (n=99, 82)	-14.5 (33.05)	-7.3 (28.70)
Insomnia: Change at C6 D1 (n=60, 59)	-8.3 (30.46)	-2.3 (30.86)
Insomnia: Change at C7 D1 (n=37, 37)	-11.7 (36.19)	-2.7 (19.84)
Insomnia: Change at C8 D1 (n=17, 21)	5.9 (35.82)	-3.2 (20.82)
Insomnia: Change at C9 D1 (n=9, 9)	-14.8 (24.23)	-0.0 (23.56)
Insomnia: Change at C10 D1 (n=3, 4)	11.1 (19.23)	-0.0 (27.23)
Insomnia: Change at C11 D1 (n=1, 1)	0.0 (NA)	33.3 (NA)
Insomnia: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Insomnia: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Insomnia: Change at follow-up (n=68, 73)	1.5 (36.63)	1.4 (28.02)
Loss of appetite: Baseline (n=297, 295)	39.6 (35.49)	37.5 (33.36)
Loss of appetite: Change at C2 D1 (n=240, 240)	-2.1 (34.24)	-2.6 (27.91)
Loss of appetite: Change at C3 D1 (n=178, 186)	-1.3 (31.57)	-5.9 (31.50)
Loss of appetite: Change at C4 D1 (n=135, 135)	0.0 (35.27)	-6.7 (29.88)
Loss of appetite: Change at C5 D1 (n=99, 82)	1.7 (35.76)	-4.5 (30.44)
Loss of appetite: Change at C6 D1 (n=60, 59)	2.8 (33.22)	-4.5 (29.34)
Loss of appetite: Change at C7 D1 (n=38, 37)	0.9 (35.92)	-7.2 (27.37)
Loss of appetite: Change at C8 D1 (n=17, 20)	7.8 (25.07)	-1.7 (29.57)
Loss of appetite: Change at C9 D1 (n=9, 9)	-14.8 (29.41)	-7.4 (36.44)
Loss of appetite: Change at C10 D1 (n=3, 4)	-22.2 (19.23)	0.0 (38.48)
Loss of appetite: Change at C11 D1 (n=1, 1)	0.0 (NA)	33.3 (NA)
Loss of appetite: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Loss of appetite: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Loss of appetite: Change at follow-up (n=67, 73)	7.0 (39.17)	7.8 (36.24)
Constipation: Baseline (n=293, 289)	30.7 (32.13)	29.6 (32.66)
Constipation: Change at C2 D1 (n=234, 235)	-4.8 (32.18)	-2.8 (33.21)
Constipation: Change at C3 D1 (n =173, 181)	-7.3 (32.12)	-6.1 (36.43)
Constipation: Change at C4 D1 (n=134, 135)	-6.5 (35.99)	-10.6 (36.80)
Constipation: Change at C5 D1 (n=97, 80)	-11.0 (33.59)	-8.7 (29.88)
Constipation: Change at C6 D1 (n=60, 58)	-5.6 (37.42)	-9.8 (32.45)
Constipation: Change at C7 D1 (n=38, 36)	-2.6 (31.37)	-13.0 (32.15)
Constipation: Change at C8 D1 (n=17, 20)	0.0 (28.87)	-16.7 (39.74)
Constipation: Change at C9 D1 (n=9, 9)	-18.5 (33.79)	-29.6 (35.14)
Constipation: Change at C10 D1 (n=3, 4)	-11.1 (19.23)	-50.0 (43.04)
Constipation: Change at C11 D1 (n=1, 1)	0.0 (NA)	-66.7 (NA)
Constipation: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Constipation: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Constipation: Change at follow-up (n=66, 71)	5.1 (42.27)	-6.1 (35.77)
Diarrhoea: Baseline (n=294, 290)	14.3 (21.68)	13.7 (24.19)
Diarrhoea: Change at C2 D1 (n=235, 235)	1.7 (25.73)	0.3 (21.78)
Diarrhoea: Change at C3 D1 (n=173, 182)	9.4 (28.66)	0.2 (23.10)
Diarrhoea: Change at C4 D1 (n=134, 136)	7.7 (28.00)	-1.5 (22.53)
Diarrhoea: Change at C5 D1 (n=96, 81)	11.8 (27.35)	1.2 (27.10)
Diarrhoea: Change at C6 D1 (n=60, 58)	20.0 (33.72)	1.7 (28.22)
Diarrhoea: Change at C7 D1 (n=38, 36)	14.9 (32.60)	2.8 (23.05)
Diarrhoea: Change at C8 D1 (n=17, 20)	25.5 (38.24)	1.7 (27.52)
Diarrhoea: Change at C9 D1 (n=9, 9)	37.0 (45.47)	22.2 (33.35)
Diarrhoea: Change at C10 D1 (n=3, 4)	22.2 (50.91)	16.7 (19.23)
Diarrhoea: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Diarrhoea: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Diarrhoea: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Diarrhoea: Change at follow-up (n=66, 71)	2.5 (29.41)	2.8 (25.03)
Financial difficulties (FD): Baseline (n=292, 285)	24.7 (30.41)	23.0 (30.83)
FD:Change at C2 D1 (n=233, 228)	-3.1 (22.95)	-4.5 (23.29)
FD: Change at C3 D1 (n=171, 176)	-7.2 (26.94)	-3.4 (23.39)
FD: Change at C4 D1 (n=133, 133)	-5.5 (26.33)	-3.3 (23.52)
FD: Change at C5 D1 (n=96, 80)	-4.9 (21.62)	1.3 (25.68)
FD: Change at C6 D1 (n=60, 56)	-3.9 (24.61)	-1.8 (28.02)
FD: Change at C7 D1 (n=37, 34)	-2.7 (24.06)	-3.9 (32.60)
FD: Change at C8 D1 (n=17, 17)	2.0 (14.28)	2.0 (34.31)
FD: Change at C9 D1 (n=9, 9)	7.4 (22.23)	3.7 (45.49)
FD: Change at C10 D1 (n=3, 4)	0.0 (0.00)	25.0 (41.94)
FD: Change at C11 D1 (n=1, 1)	0.0 (NA)	66.7 (NA)
FD: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
FD: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
FD: Change at follow-up (n=65, 70)	6.7 (29.59)	-0.5 (21.61)
GHS/Quality of Life (QoL): Baseline (n=292, 288)	54.2 (22.34)	57.1 (23.14)
GHS/QoL:Change at C2 D1 (n=234, 233)	2.2 (23.36)	1.9 (22.39)
GHS/QoL:Change at C3 D1 (n=168, 180)	-0.3 (25.42)	5.7 (21.45)
GHS/QoL:Change at C4 D1(n=132, 132)	0.1 (23.79)	2.8 (21.54)
GHS/QoL:Change at C5 D1 (n=96, 81)	1.5 (22.63)	2.7 (18.35)
GHS/QoL:Change at C6 D1 (n=60, 57)	0.8 (21.41)	3.2 (23.40)
GHS/QoL:Change at C7 D1 (n=38, 35)	2.6 (23.01)	2.1 (22.35)
GHS/QoL:Change at C8 D1 (n=17, 19)	-1.0 (23.73)	1.3 (23.76)
GHS/QoL:Change at C9 D1 (n=9, 9)	7.4 (16.89)	-8.3 (20.39)
GHS/QoL: Change at C10 D1 (n=3, 4)	22.3 (19.28)	-0.0 (32.59)
GHS/QoL: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
GHS/QoL: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
GHS/QoL: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
GHS/QoL:Change at follow-up (n=65, 71)	-9.1 (26.06)	-6.7 (24.50)

6. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score
Description	QLQ-PAN26 consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC). Questions include on altered bowel habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC. All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100; higher scores= greater degree of symptoms or treatment side effects and emotional issues.
Time Frame	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Pancreatic Pain: Baseline (n=246, 250)	41.6 (27.16)	40.0 (25.54)
Pancreatic Pain: Change at C2 D1 (n=191, 197)	-10.9 (24.38)	-10.1 (22.93)
Pancreatic Pain: Change at C3 D1 (n=141, 153)	-16.3 (25.51)	-11.2 (24.92)
Pancreatic Pain: Change at C4 D1 (n=99, 111)	-13.2 (28.70)	-11.4 (26.16)
Pancreatic Pain: Change at C5 D1 (n=67, 64)	-15.8 (28.06)	-13.0 (23.85)
Pancreatic Pain: Change at C6 D1 (n=41, 43)	-15.9 (25.47)	-13.0 (24.62)
Pancreatic Pain: Change at C7 D1 (n=25, 25)	-15.3 (28.02)	-15.0 (25.69)
Pancreatic Pain: Change at C8 D1 (n=11, 11)	-7.6 (27.76)	-9.8 (30.01)
Pancreatic Pain: Change at C9 D1 (n=6, 6)	-29.2 (31.06)	0.0 (15.81)
Pancreatic Pain: Change at C10 D1 (n=2, 3)	-20.9 (29.49)	5.6 (26.79)
Pancreatic Pain: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Pancreatic Pain: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pancreatic Pain: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pancreatic Pain: Change at follow-up (n=47, 46)	-3.5 (29.59)	-3.6 (28.80)
Hepatic: Baseline (n=245, 254)	10.2 (17.21)	10.8 (17.59)
Hepatic: Change at C2 D1 (n=193, 205)	0.3 (18.24)	-2.0 (17.67)
Hepatic: Change at C3 D1 (n=142, 157)	-1.4 (16.78)	-2.5 (18.60)
Hepatic: Change at C4 D1 (n=99, 112)	-2.5 (18.34)	-2.4 (18.15)
Hepatic: Change at C5 D1 (n=68, 64)	1.0 (17.49)	-2.6 (16.60)
Hepatic: Change at C6 D1 (n=40, 41)	0.4 (15.34)	-3.2 (17.57)
Hepatic: Change at C7 D1 (n=25, 24)	-0.7 (16.30)	-4.9 (18.70)
Hepatic: Change at C8 D1 (n=11, 12)	-4.5 (13.10)	-4.2 (12.57)
Hepatic: Change at C9 D1 (n=6, 5)	-11.1 (13.60)	-13.3 (13.94)
Hepatic: Change at C10 D1 (n=2, 2)	-16.7 (23.55)	-8.4 (11.81)
Hepatic: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Hepatic: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Hepatic: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Hepatic: Change at follow-up (n=47, 48)	2.8 (23.38)	-1.4 (23.27)
Digestive Symptom: Baseline (n=250, 255)	34.3 (30.78)	33.9 (31.05)
Digestive Symptom: Change at C2 D1 (n=195, 206)	2.8 (29.15)	0.6 (26.72)
Digestive Symptom: Change at C3 D1 (n=144, 159)	-1.2 (31.58)	-4.3 (32.97)
Digestive Symptom: Change at C4 D1 (n=100, 114)	0.5 (30.57)	-4.5 (30.90)
Digestive Symptom: Change at C5 D1 (n=69, 65)	1.4 (32.80)	-3.6 (36.14)
Digestive Symptom: Change at C6 D1 (n=40, 45)	3.3 (30.23)	0.4 (35.97)
Digestive Symptom: Change at C7 D1 (n=25, 26)	-6.0 (30.76)	-1.3 (24.91)
Digestive Symptom: Change at C8 D1 (n=11, 14)	4.5 (42.87)	17.9 (23.07)
Digestive Symptom: Change at C9 D1 (n=6, 6)	-13.9 (46.44)	22.2 (25.10)
Digestive Symptom: Change at C10 D1 (n=2, 3)	-33.3 (47.09)	11.1 (19.23)
Digestive Symptom: Change at C11 D1 (n=1, 1)	0.0 (NA)	66.7 (NA)
Digestive Symptom: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Digestive Symptom: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Digestive Symptom: Change at follow-up (n=47, 47)	6.0 (38.14)	2.8 (35.83)
Sexuality: Baseline (n=217, 232)	56.8 (36.90)	55.5 (38.04)
Sexuality: Change at C2 D1 (n=157, 181)	-0.5 (37.81)	-4.0 (33.17)
Sexuality: Change at C3 D1 (n=118, 139)	-4.9 (37.70)	-3.0 (32.25)
Sexuality: Change at C4 D1 (n=85, 100)	-4.1 (38.40)	3.0 (29.90)
Sexuality: Change at C5 D1 (n=55, 58)	-1.5 (34.30)	-5.2 (29.32)
Sexuality: Change at C6 D1 (n=30, 38)	12.2 (29.67)	-11.4 (33.58)
Sexuality: Change at C7 D1 (n=19, 21)	4.4 (35.06)	-7.1 (31.88)
Sexuality: Change at C8 D1 (n=8, 10)	12.5 (24.82)	-15.0 (26.59)
Sexuality: Change at C9 D1 (n=4, 6)	25.0 (31.93)	0.0 (23.55)
Sexuality: Change at C10 D1 (n=0, 3)	NA (NA)	11.1 (19.28)
Sexuality: Change at C11 D1 (n=0, 1)	NA (NA)	33.3 (NA)
Sexuality: Change at C12 D1 (n=0, 0)	NA (NA)	NA (NA)
Sexuality: Change at C13 D1 (n=0, 0)	NA (NA)	NA (NA)
Sexuality: Change at follow-up (n=36, 41)	-3.2 (41.18)	-23.2 (42.31)
Health care(HC)satisfaction: Baseline (n=241, 247)	78.0 (26.66)	78.3 (23.94)
HC satisfaction: Change at C2 D1 (n=182, 194)	0.1 (27.73)	1.8 (24.13)
HC satisfaction: Change at C3 D1 (n=135, 149)	0.2 (31.54)	5.4 (24.98)
HC satisfaction: Change at C4 D1 (n=97, 108)	-4.3 (34.88)	-0.2 (26.52)
HC satisfaction: Change at C5 D1 (n=66, 59)	1.0 (29.66)	0.8 (28.77)
HC satisfaction: Change at C6 D1 (n=40, 39)	-6.7 (26.91)	-0.4 (27.96)
HC satisfaction: Change at C7 D1 (n=27, 20)	-4.3 (22.44)	6.7 (33.06)
HC satisfaction: Change at C8 D1 (n=12, 11)	-16.7 (52.23)	7.6 (20.22)
HC satisfaction: Change at C9 D1 (n=6, 6)	16.7 (47.14)	-5.6 (17.23)
HC satisfaction: Change at C10 D1 (n=2, 3)	-33.3 (0.0)	5.6 (9.64)
HC satisfaction: Change at C11 D1 (n=1, 1)	-33.3 (NA)	0.0 (NA)
HC satisfaction: Change at C12 D1 (n=1, 0)	-33.3 (NA)	NA (NA)
HC satisfaction: Change at C13 D1(n=1, 0)	-33.3 (NA)	NA (NA)
HC satisfaction: Change at follow-up (n=46, 45)	-0.7 (29.39)	-2.2 (31.50)
Body Image: Baseline (n=249, 251)	28.5 (28.46)	28.8 (28.67)
Body Image: Change at C2 D1 (n=189, 200)	4.9 (23.11)	-0.2 (26.78)
Body Image: Change at C3 D1 (n=142, 149)	4.9 (22.26)	2.1 (26.16)
Body Image: Change at C4 D1 (n=97, 111)	6.7 (26.20)	0.9 (26.48)
Body Image: Change at C5 D1 (n=70, 62)	4.8 (26.33)	-0.3 (25.87)
Body Image: Change at C6 D1 (n=40, 42)	8.3 (28.24)	-0.8 (33.92)
Body Image: Change at C7 D1 (n=25, 24)	12.0 (27.43)	-5.6 (33.22)
Body Image: Change at C8 D1 (n=11, 12)	21.2 (42.23)	11.1 (32.04)
Body Image: Change at C9 D1 (n=6, 6)	33.3 (52.69)	8.3 (46.87)
Body Image: Change at C10 D1 (n=2, 3)	-8.3 (11.74)	5.6 (78.77)
Body Image: Change at C11 D1 (n=1, 1)	0.0 (NA)	-50.0 (NA)
Body Image: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Body Image: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Body Image: Change at follow-up (n=47, 45)	13.1 (30.67)	11.5 (24.56)
Altered Bowel Habit: Baseline (n=250, 255)	20.3 (22.92)	21.2 (25.72)
Altered Bowel Habit: Change at C2 D1 (n=193, 204)	3.0 (24.19)	1.5 (22.21)
Altered Bowel Habit: Change at C3 D1 (n=143, 156)	6.2 (26.37)	2.5 (24.67)
Altered Bowel Habit: Change at C4 D1 (n=98, 114)	6.6 (25.52)	4.8 (22.14)
Altered Bowel Habit: Change at C5 D1 (n=68, 63)	8.3 (33.15)	1.3 (24.56)
Altered Bowel Habit: Change at C6 D1 (n=40, 43)	9.6 (30.63)	2.3 (28.07)
Altered Bowel Habit: Change at C7 D1 (n=25, 25)	6.0 (25.40)	1.3 (30.77)
Altered Bowel Habit: Change at C8 D1 (n=11, 13)	1.5 (29.29)	7.7 (38.86)
Altered Bowel Habit: Change at C9 D1 (n=6, 6)	13.9 (32.35)	-5.6 (51.27)
Altered Bowel Habit: Change at C10 D1 (n=2, 3)	-8.3 (35.36)	-16.7 (72.62)
Altered Bowel Habit: Change at C11 D1 (n=1, 1)	16.7 (NA)	-100.0 (NA)
Altered Bowel Habit: Change at C12 D1 (n=1, 0)	16.7 (NA)	NA (NA)
Altered Bowel Habit: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Altered Bowel Habit: Change at followup (n=47, 48)	6.0 (29.36)	5.9 (21.33)
Ascites: Baseline (n=250, 256)	38.7 (32.98)	32.9 (30.61)
Ascites: Change at C2 D1 (n=197, 207)	-8.6 (33.32)	-3.4 (29.65)
Ascites: Change at C3 D1 (n=144, 158)	-8.3 (33.34)	-5.1 (28.70)
Ascites: Change at C4 D1 (n=101, 114)	-5.0 (36.64)	-0.3 (26.05)
Ascites: Change at C5 D1 (n=71, 65)	-8.5 (34.15)	-0.5 (29.17)
Ascites: Change at C6 D1 (n=42, 45)	-3.2 (31.08)	-2.2 (32.10)
Ascites: Change at C7 D1 (n=26, 26)	-14.1 (32.91)	-12.8 (23.25)
Ascites: Change at C8 D1 (n=11, 14)	-18.2 (43.12)	-11.9 (28.05)
Ascites: Change at C9 D1 (n=6, 6)	-11.1 (34.42)	-16.7 (34.95)
Ascites: Change at C10 D1 (n=2, 3)	-16.7 (23.55)	22.2 (38.51)
Ascites: Change at C11 D1 (n=1, 1)	0.0 (NA)	33.3 (NA)
Ascites: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Ascites: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Ascites: Change at follow-up (n=48, 48)	5.6 (35.96)	-2.1 (26.11)
Indigestion: Baseline (n=252, 257)	29.4 (30.38)	24.0 (28.55)
Indigestion: Change at C2 D1 (n=198, 208)	-0.3 (26.87)	-2.4 (24.29)
Indigestion: Change at C3 D1 (n=144, 159)	0.2 (30.16)	-5.2 (25.59)
Indigestion: Change at C4 D1 (n=101, 115)	-4.0 (24.63)	-4.1 (25.80)
Indigestion: Change at C5 D1 (n=71, 65)	0.5 (29.01)	-4.6 (22.72)
Indigestion: Change at C6 D1 (n=41, 45)	1.6 (31.58)	-1.5 (24.57)
Indigestion: Change at C7 D1 (n=26, 26)	-3.8 (19.60)	-1.3 (17.59)
Indigestion: Change at C8 D1 (n=11, 14)	0.0 (21.06)	2.4 (20.53)
Indigestion: Change at C9 D1 (n=6, 6)	-5.6 (25.07)	11.1 (27.23)
Indigestion: Change at C10 D1 (n=2, 3)	-16.7 (23.55)	22.2 (19.23)
Indigestion: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Indigestion: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Indigestion: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Indigestion: Change at follow-up (n=48, 48)	7.6 (30.94)	1.4 (30.73)
Flatulence: Baseline (n=249, 256)	37.9 (32.34)	34.0 (31.31)
Flatulence: Change at C2 D1 (n=197, 206)	1.2 (29.81)	2.6 (31.82)
Flatulence: Change at C3 D1 (n=146, 159)	3.2 (33.07)	0.2 (34.48)
Flatulence: Change at C4 D1 (n=101, 115)	-1.3 (33.65)	2.3 (32.07)
Flatulence: Change at C5 D1 (n=70, 65)	-1.0 (32.60)	1.0 (31.17)
Flatulence: Change at C6 D1 (n=41, 45)	-1.6 (26.83)	-1.5 (29.27)
Flatulence: Change at C7 D1 (n=25, 26)	-1.3 (26.31)	-3.8 (23.71)
Flatulence: Change at C8 D1 (n=10, 14)	-10.0 (35.34)	2.4 (27.62)
Flatulence: Change at C9 D1 (n=5, 6)	0.0 (0.00)	5.6 (13.59)
Flatulence: Change at C10 D1 (n=1, 3)	33.3 (NA)	-11.1 (19.23)
Flatulence: Change at C11 D1 (n=0, 1)	NA (NA)	0.0 (NA)
Flatulence: Change at C12 D1 (n=0, 0)	NA (NA)	NA (NA)
Flatulence: Change at C13 D1 (n=0, 0)	NA (NA)	NA (NA)
Flatulence: Change at follow-up (n=48, 46)	-0.7 (35.41)	2.2 (34.00)
Cachexia: Baseline (n=251, 253)	33.1 (27.62)	33.6 (26.84)
Cachexia: Change at C2 D1 (n=197, 205)	4.2 (24.26)	0.6 (21.63)
Cachexia: Change at C3 D1 (n=145, 157)	4.6 (25.87)	-3.3 (21.13)
Cachexia: Change at C4 D1 (n=101, 112)	1.2 (26.37)	-6.2 (24.82)
Cachexia: Change at C5 D1 (n=70, 64)	0.5 (28.37)	-8.3 (24.48)
Cachexia: Change at C6 D1 (n=40, 44)	-2.1 (24.80)	-5.3 (24.84)
Cachexia: Change at C7 D1 (n=24, 26)	-0.7 (24.31)	-5.1 (25.27)
Cachexia: Change at C8 D1 (n=10, 14)	15.0 (34.64)	-4.7 (21.12)
Cachexia: Change at C9 D1 (n=5, 6)	16.7 (31.16)	2.8 (19.47)
Cachexia: Change at C10 D1 (n=1, 3)	0.0 (NA)	0.0 (28.87)
Cachexia: Change at C11 D1 (n=0, 1)	NA (NA)	-16.6 (NA)
Cachexia: Change at C12 D1 (n=0, 0)	NA (NA)	NA (NA)
Cachexia: Change at C13 D1 (n=0, 0)	NA (NA)	NA (NA)
Cachexia: Change at follow-up (n=48, 47)	8.0 (31.69)	6.4 (30.79)
Side Effects: Baseline (n=209, 226)	24.9 (21.21)	27.4 (23.08)
Side Effects: Change at C2 D1 (n=159, 181)	11.2 (23.11)	5.8 (22.06)
Side Effects: Change at C3 D1 (n=113, 137)	13.0 (24.67)	4.7 (22.18)
Side Effects: Change at C4 D1 (n=80, 102)	10.1 (20.64)	4.9 (22.48)
Side Effects: Change at C5 D1 (n=54, 59)	7.4 (25.55)	3.6 (23.84)
Side Effects: Change at C6 D1 (n=29, 40)	8.1 (26.72)	-1.4 (25.32)
Side Effects: Change at C7 D1 (n=17, 22)	15.0 (20.77)	-1.0 (19.38)
Side Effects: Change at C8 D1 (n=8, 11)	9.7 (19.19)	-3.0 (22.83)
Side Effects: Change at C9 D1 (n=3, 6)	14.8 (23.15)	-1.9 (27.60)
Side Effects: Change at C10 D1 (n=0, 3)	NA (NA)	0.0 (40.12)
Side Effects: Change at C11 D1 (n=0, 1)	NA (NA)	-33.4 (NA)
Side Effects: Change at C12 D1 (n=0, 0)	NA (NA)	NA (NA)
Side Effects: Change at C13 D1 (n=0, 0)	NA (NA)	NA (NA)
Side Effects: Change at follow-up (n=42, 42)	18.8 (24.37)	13.2 (27.80)
Fear of Future Health (FH): Baseline (n=252, 250))	59.3 (31.33)	61.1 (33.07)
Fear of FH: Change at C2 D1 (n=192, 201)	-3.5 (31.82)	-9.6 (28.80)
Fear of FH: Change at C3 D1 (n=145, 155)	-0.9 (34.02)	-11.6 (30.07)
Fear of FH: Change at C4 D1 (n=103, 113)	-4.5 (32.70)	-15.9 (30.90)
Fear of FH: Change at C5 D1 (n=71, 64)	-0.5 (31.12)	-10.9 (29.74)
Fear of FH: Change at C6 D1 (n=42, 44)	-4.8 (30.86)	-14.4 (32.47)
Fear of FH: Change at C7 D1 (n=27, 25)	-6.2 (22.72)	-13.3 (33.34)
Fear of FH: Change at C8 D1 (n=12, 12)	2.8 (30.02)	5.6 (27.84)
Fear of FH: Change at C9 D1 (n=6, 6)	16.7 (27.90)	16.7 (34.96)
Fear of FH: Change at C10 D1 (n=2, 3)	-16.7 (23.62)	11.1 (50.96)
Fear of FH: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Fear of FH: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Fear of FH: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Fear of FH:Change at follow-up (n=48, 45)	5.6 (28.63)	-4.4 (38.67)
Future Plan ability: Baseline (n=250, 249)	34.3 (33.59)	38.0 (34.40)
Future Plan ability: Change at C2 D1 (n=192, 198)	6.1 (38.19)	-0.3 (34.58)
Future Plan ability:Change at C3 D1 (n=142, 153)	3.5 (39.65)	0.4 (36.68)
Future Plan ability:Change at C4 D1 (n=101, 112)	5.6 (36.55)	0.3 (37.04)
Future Plan ability:Change at C5 D1 (n=70, 62)	0.9 (34.05)	-3.8 (39.17)
Future Plan ability:Change at C6 D1 (n=42, 42)	4.8 (34.99)	0.8 (46.27)
Future Plan ability: Change at C7 D1 (n=26, 24)	2.6 (28.18)	-7.0 (36.76)
Future Plan ability: Change at C8 D1 (n=11, 11)	6.1 (32.74)	3.0 (43.36)
Future Plan ability: Change at C9 D1 (n=5, 6)	0.0 (23.55)	0.0 (55.78)
Future Plan ability: Change at C10 D1 (n=1, 3)	0.0 (NA)	-11.1 (69.43)
Future Plan ability: Change at C11 D1 (n=1, 1)	0.0 (NA)	-66.7 (NA)
Future Plan ability: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Future Plan ability: Change at C13 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Future Plan ability: Change at followup (n=48, 45)	21.5 (35.40)	5.2 (38.25)

7. Secondary Outcome

Title	Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score
Description	BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Time Frame	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Worst Pain: Baseline (n=247, 250)	3.8 (2.84)	3.7 (2.96)
Worst Pain: Change at C2 D1 (n=192, 200)	-0.7 (3.04)	-0.9 (2.84)
Worst Pain: Change at C3 D1 (n=138, 151)	-1.5 (3.09)	-0.9 (2.83)
Worst Pain: Change at C4 D1 (n=99, 113)	-1.0 (3.41)	-0.9 (3.09)
Worst Pain: Change at C5 D1 (n=69, 64)	-1.1 (3.43)	-1.2 (3.08)
Worst Pain: Change at C6 D1 (n=41, 43)	-0.9 (2.98)	-1.0 (3.17)
Worst Pain: Change at C7 D1 (n=25, 26)	-0.8 (2.27)	-0.9 (3.50)
Worst Pain: Change at C8 D1 (n=12, 13)	0.8 (2.56)	-1.5 (3.20)
Worst Pain: Change at C9 D1(n=6, 6)	-1.8 (1.94)	-1.3 (1.51)
Worst Pain: Change at C10 D1 (n=2, 3)	-2.0 (2.83)	-0.3 (2.31)
Worst Pain: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Worst Pain: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Worst Pain: Change at C13 D1 (n=1, 1)	0.0 (NA)	-4.0 (NA)
Worst Pain: Change at follow-up (n=47, 46)	0.5 (3.08)	0.0 (3.21)
Pain in Last 24 Hours (hrs): Baseline (n=246, 248)	1.8 (1.92)	1.7 (1.93)
Pain in Last 24 hrs: Change at C2 D1 (n=193, 197)	-0.2 (2.21)	-0.3 (1.92)
Pain in Last 24 hrs: Change at C3 D1 (n=138, 150)	-0.6 (2.01)	-0.3 (1.88)
Pain in Last 24 hrs: Change at C4 D1 (n=99, 112)	-0.3 (2.15)	-0.0 (1.96)
Pain in Last 24 hrs: Change at C5 D1 (n=69, 63)	-0.3 (2.41)	-0.2 (2.04)
Pain in Last 24 hrs: Change at C6 D1 (n=40, 43)	-0.2 (2.07)	-0.1 (1.64)
Pain in Last 24 hrs: Change at C7 D1 (n=25, 26)	0.4 (1.47)	-0.0 (2.46)
Pain in Last 24 hrs: Change at C8 D1 (n=12, 13)	1.3 (2.34)	-0.2 (1.41)
Pain in Last 24 hrs: Change at C9 D1 (n=6, 6)	-0.3 (1.37)	0.2 (1.60)
Pain in Last 24 hrs: Change at C10 D1 (n=2, 3)	-1.5 (2.12)	0.3 (0.58)
Pain in Last 24 hrs: Change at C11 D1 (n=1, 1)	0.0 (NA)	4.0 (NA)
Pain in Last 24 hrs: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pain in Last 24 hrs: Change at C13 D1 (n=1, 1)	0.0 (NA)	-1.0 (NA)
Pain in Last 24 hrs: Change at followup (n=48, 45)	0.4 (2.70)	0.8 (2.58)
Pain on the Average: Baseline (n=246, 248)	2.9 (2.16)	2.8 (2.27)
Pain on the Average: Change at C2 D1 (n=195, 198)	-0.5 (2.02)	-0.5 (2.29)
Pain on the Average: Change at C3 D1 (n=140, 149)	-0.8 (2.48)	-0.5 (2.10)
Pain on the Average: Change at C4 D1 (n=99, 113)	-0.7 (2.44)	-0.6 (2.03)
Pain on the Average: Change at C5 D1 (n=69, 63)	-0.7 (2.48)	-0.6 (2.29)
Pain on the Average: Change at C6 D1 (n=40, 43)	-0.5 (2.07)	-0.9 (2.12)
Pain on the Average: Change at C7 D1 (n=25, 26)	-0.3 (1.46)	-0.5 (2.97)
Pain on the Average: Change at C8 D1 (n=12, 13)	1.0 (2.00)	-1.4 (1.94)
Pain on the Average: Change at C9 D1 (n=6, 6)	-1.7 (1.51)	-1.7 (1.86)
Pain on the Average: Change at C10 D1 (n=2, 3)	-2.0 (2.83)	-1.0 (2.65)
Pain on the Average: Change at C11 D1 (n=1, 1)	0.0 (NA)	-3.0 (NA)
Pain on the Average: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pain on the Average: Change at C13 D1 (n=1, 1)	0.0 (NA)	-2.0 (NA)
Pain on the Average: Change at followup (n=48, 45)	0.6 (2.70)	0.4 (2.74)
Pain Right Now: Baseline (n=248, 249)	2.1 (2.13)	2.1 (2.36)
Pain Right Now: Change at C2 D1 (n=196, 200)	-0.4 (2.23)	-0.5 (2.37)
Pain Right Now: Change at C3 D1 (n=140, 150)	-0.8 (2.31)	-0.6 (2.06)
Pain Right Now: Change at C4 D1 (n=99, 113)	-0.6 (2.26)	-0.5 (2.45)
Pain Right Now: Change at C5 D1 (n=68, 63)	-0.5 (2.76)	-0.3 (2.65)
Pain Right Now: Change at C6 D1 (n=40, 43)	-0.5 (1.96)	-0.5 (2.14)
Pain Right Now: Change at C7 D1 (n=25, 26)	0.1 (1.66)	-0.2 (3.26)
Pain Right Now: Change at C8 D1 (n=12, 13)	1.1 (1.93)	-0.6 (1.56)
Pain Right Now: Change at C9 D1 (n=6, 6)	-1.5 (1.76)	-0.3 (0.52)
Pain Right Now: Change at C10 D1 (n=2, 3)	-2.0 (2.83)	0.7 (1.15)
Pain Right Now: Change at C11 D1 (n=1, 1)	0.0 (NA)	5.0 (NA)
Pain Right Now: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Pain Right Now: Change at C13 D1 (n=1, 1)	0.0 (NA)	-5.0 (NA)
Pain Right Now: Change at follow-up (n=48, 46)	0.4 (2.64)	-0.0 (2.67)
Relief Pain Treatment (Tx): Baseline (n=226, 221)	7.8 (12.09)	6.9 (9.71)
Relief Pain Tx: Change at C2 D1 (n=164, 165)	0.6 (13.96)	0.4 (11.48)
Relief Pain Tx: Change at C3 D1 (n=122, 124)	-2.1 (13.10)	0.1 (9.16)
Relief Pain Tx: Change at C4 D1 (n=88, 92)	-1.7 (13.51)	-0.9 (17.56)
Relief Pain Tx: Change at C5 D1 (n=59, 51)	-2.9 (16.35)	1.8 (11.62)
Relief Pain Tx: Change at C6 D1 (n=34, 33)	-1.6 (11.90)	0.5 (4.28)
Relief Pain Tx: Change at C7 D1 (n=21, 18)	1.0 (2.78)	-3.2 (19.65)
Relief Pain Tx: Change at C8 D1 (n=10, 8)	-5.0 (21.20)	-11.6 (28.16)
Relief Pain Tx: Change at C9 D1 (n=5, 5)	-14.0 (28.99)	-16.6 (35.44)
Relief Pain Tx: Change at C10 D1 (n=1, 2)	6.0 (NA)	0.0 (1.41)
Relief Pain Tx: Change at C11 D1 (n=0, 1)	NA (NA)	0.0 (NA)
Relief Pain Tx: Change at C12 D1 (n=0, 0)	NA (NA)	NA (NA)
Relief Pain Tx: Change at C13 D1 (n=0, 0)	NA (NA)	NA (NA)
Relief Pain Tx: Change at follow-up (n=43, 36)	0.2 (3.82)	-0.4 (5.08)
General Activity: Baseline (n=243, 243)	3.2 (3.11)	3.0 (3.01)
General Activity: Change at C2 D1 (n=190, 193)	-0.6 (2.96)	-0.7 (2.55)
General Activity: Change at C3 D1 (n=135, 143)	-1.1 (3.47)	-0.7 (2.61)
General Activity: Change at C4 D1 (n=97, 109)	-0.4 (3.10)	-0.8 (2.53)
General Activity: Change at C5 D1 (n=66, 62)	-0.8 (3.64)	-0.5 (2.51)
General Activity: Change at C6 D1 (n=40, 41)	-0.6 (3.82)	-0.7 (2.62)
General Activity: Change at C7 D1 (n=25, 25)	-0.5 (2.87)	-0.4 (2.84)
General Activity: Change at C8 D1 (n=12, 12)	0.1 (2.07)	-0.8 (2.70)
General Activity: Change at C9 D1 (n=6, 6)	-2.2 (2.71)	0.3 (3.72)
General Activity: Change at C10 D1 (n=2, 3)	-2.5 (3.54)	3.0 (5.29)
General Activity: Change at C11 D1 (n=1, 1)	0.0 (NA)	1.0 (NA)
General Activity: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
General Activity: Change at C13 D1 (n=1, 1)	0.0 (NA)	-1.0 (NA)
General Activity: Change at follow-up (n=47, 44)	1.0 (4.32)	0.0 (3.63)
Mood: Baseline (n=243, 241)	3.0 (2.92)	2.8 (2.77)
Mood: Change at C2 D1 (n=191, 191)	-0.6 (2.74)	-0.2 (2.46)
Mood: Change at C3 D1 (n=135, 141)	-1.0 (3.39)	-0.5 (2.51)
Mood: Change at C4 D1 (n=98, 106)	-0.3 (3.22)	-0.9 (2.81)
Mood: Change at C5 D1 (n=66, 61)	-0.7 (3.66)	-0.9 (2.59)
Mood: Change at C6 D1 (n=40, 41)	-0.6 (3.23)	-0.8 (2.93)
Mood: Change at C7 D1 (n=25, 25)	0.0 (2.54)	-0.2 (3.18)
Mood: Change at C8 D1 (n=12, 12)	0.6 (1.31)	-1.1 (3.12)
Mood: Change at C9 D1 (n=6, 6)	-1.3 (1.97)	-0.8 (3.31)
Mood: Change at C10 D1 (n=2, 3)	-1.0 (1.41)	3.3 (1.53)
Mood: Change at C11 D1 (n=1, 1)	0.0 (NA)	5.0 (NA)
Mood: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Mood: Change at C13 D1 (n=1, 1)	0.0 (NA)	-3.0 (NA)
Mood: Change at follow-up (n=47, 44)	0.9 (3.65)	0.2 (3.62)
Walking Ability: Baseline (n=242, 243)	2.2 (2.78)	2.3 (2.81)
Walking Ability: Change at C2 D1 (n=189, 194)	0.1 (2.84)	-0.1 (2.61)
Walking Ability: Change at C3 D1 (n=133, 143)	-0.2 (3.41)	-0.3 (2.52)
Walking Ability: Change at C4 D1 (n=97, 108)	0.3 (3.32)	-0.4 (2.64)
Walking Ability: Change at C5 D1 (n=66, 62)	0.1 (3.49)	-0.3 (2.37)
Walking Ability: Change at C6 D1 (n=41, 41)	0.5 (2.86)	-0.2 (2.24)
Walking Ability: Change at C7 D1 (n=25, 25)	1.1 (2.67)	-0.1 (2.42)
Walking Ability: Change at C8 D1 (n=12, 12)	0.7 (2.46)	-1.3 (2.42)
Walking Ability: Change at C9 D1 (n=6, 6)	-1.0 (3.52)	0.2 (4.62)
Walking Ability: Change at C10 D1 (n=2, 3)	-2.0 (2.83)	1.3 (5.51)
Walking Ability: Change at C11 D1 (n=1, 1)	0.0 (NA)	0.0 (NA)
Walking Ability: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Walking Ability: Change at C13 D1 (n=1, 1)	0.0 (NA)	-2.0 (NA)
Walking Ability: Change at follow-up (n=47, 45)	0.9 (4.13)	0.7 (3.27)
Normal Work: Baseline (n=240, 240)	3.5 (3.34)	3.2 (3.23)
Normal Work: Change at C2 D1 (n=187, 191)	-0.4 (3.24)	-0.1 (3.16)
Normal Work: Change at C3 D1 (n=133, 139)	-0.6 (3.33)	-0.4 (2.67)
Normal Work: Change at C4 D1 (n=96, 107)	-0.2 (3.15)	-0.7 (2.90)
Normal Work: Change at C5 D1 (n=65, 61)	-0.7 (3.86)	-0.6 (2.71)
Normal Work: Change at C6 D1 (n=39, 41)	0.2 (3.62)	-0.2 (3.12)
Normal Work: Change at C7 D1 (n=25, 24)	0.5 (2.76)	-0.4 (2.52)
Normal Work: Change at C8 D1 (n=12, 12)	-0.3 (3.70)	-0.1 (3.37)
Normal Work: Change at C9 D1 (n=6, 6)	-1.5 (3.51)	3.5 (4.32)
Normal Work: Change at C10 D1 (n=2, 3)	-0.5 (0.71)	1.3 (3.51)
Normal Work: Change at C11 D1 (n=1, 1)	0.0 (NA)	2.0 (NA)
Normal Work: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Normal Work: Change at C13 D1 (n=1, 1)	0.0 (NA)	-2.0 (NA)
Normal Work: Change at follow-up (n=46, 43)	1.0 (4.54)	0.3 (3.90)
Relations: Baseline (n=244, 242)	2.3 (2.93)	1.9 (2.44)
Relations: Change at C2 D1 (n=190, 193)	-0.3 (2.82)	0.0 (2.18)
Relations: Change at C3 D1 (n=136, 142)	-0.4 (3.81)	-0.0 (2.16)
Relations: Change at C4 D1 (n=98, 108)	-0.2 (3.36)	-0.1 (2.52)
Relations: Change at C5 D1 (n=66, 62)	-0.6 (3.11)	-0.1 (2.27)
Relations: Change at C6 D1 (n=40, 41)	-0.3 (4.01)	-0.1 (2.76)
Relations: Change at C7 D1 (n=25, 25)	0.8 (3.32)	-0.7 (2.44)
Relations: Change at C8 D1 (n=12, 12)	0.6 (2.61)	-0.9 (2.35)
Relations: Change at C9 D1 (n=6, 6)	-1.2 (2.93)	0.8 (4.88)
Relations: Change at C10 D1 (n=2, 3)	1.0 (1.41)	2.7 (2.52)
Relations: Change at C11 D1 (n=1, 1)	0.0 (NA)	2.0 (NA)
Relations: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Relations: Change at C13 D1 (n=1, 1)	0.0 (NA)	-2.0 (NA)
Relations: Change at follow-up (n=47, 45)	0.7 (3.94)	0.8 (3.56)
Sleep: Baseline (n=244, 242)	3.3 (3.16)	3.2 (3.17)
Sleep: Change at C2 D1 (n=191, 193)	-1.1 (3.36)	-0.9 (2.73)
Sleep: Change at C3 D1 (n=136, 142)	-1.6 (3.52)	-1.1 (2.89)
Sleep: Change at C4 D1 (n=98, 107)	-1.2 (3.29)	-1.2 (3.02)
Sleep: Change at C5 D1 (n=66, 62)	-1.3 (4.06)	-0.8 (3.37)
Sleep: Change at C6 D1(n=39, 41)	-1.5 (3.22)	-0.8 (3.62)
Sleep: Change at C7 D1 (n=25, 25)	-0.2 (3.61)	-0.6 (2.81)
Sleep: Change at C8 D1 (n=12, 12)	0.6 (2.71)	-1.2 (3.51)
Sleep: Change at C9 D1 (n=6, 6)	-2.3 (3.20)	0.3 (2.07)
Sleep: Change at C10 D1 (n=2, 3)	1.0 (1.41)	0.7 (3.51)
Sleep: Change at C11 D1 (n=1, 1)	0.0 (NA)	4.0 (NA)
Sleep: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Sleep: Change at C13 D1 (n=1, 1)	0.0 (NA)	-5.0 (NA)
Sleep: Change at follow-up (n=47, 44)	0.5 (3.65)	-0.3 (3.54)
Enjoyment of Life: Baseline (n=242, 240)	3.5 (3.34)	3.4 (3.17)
Enjoyment of Life: Change at C2 D1 (n=191, 191)	-0.6 (2.99)	-0.5 (2.89)
Enjoyment of Life: Change at C3 D1 (n=134, 142)	-0.7 (3.64)	-0.7 (2.77)
Enjoyment of Life: Change at C4 D1 (n=98, 107)	-0.6 (3.58)	-0.9 (2.70)
Enjoyment of Life: Change at C5 D1 (n=66, 62)	-0.6 (4.03)	-0.8 (3.07)
Enjoyment of Life: Change at C6 D1 (n=40, 41)	-0.4 (3.87)	-1.0 (3.17)
Enjoyment of Life: Change at C7 D1 (n=25, 25)	0.4 (3.53)	-0.9 (2.28)
Enjoyment of Life: Change at C8 D1 (n=12, 12)	0.8 (2.98)	-0.8 (2.53)
Enjoyment of Life: Change at C9 D1 (n=6, 6)	-0.5 (5.01)	0.2 (2.86)
Enjoyment of Life: Change at C10 D1 (n=2, 3)	0.5 (0.71)	2.3 (5.51)
Enjoyment of Life: Change at C11 D1 (n=1, 1)	0.0 (NA)	-1.0 (NA)
Enjoyment of Life: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Enjoyment of Life: Change at C13 D1 (n=1, 1)	0.0 (NA)	-4.0 (NA)
Enjoyment of Life: Change at follow-up (n=47, 43)	0.2 (3.68)	-0.2 (3.99)
Combined Pain Intensity(PI): Baseline (n=248, 251)	2.7 (1.98)	2.6 (2.12)
Combined PI: Change at C2 D1 (n=196, 202)	-0.4 (1.97)	-0.5 (1.97)
Combined PI: Change at C3 D1 (n=140, 151)	-0.9 (2.15)	-0.6 (1.88)
Combined PI: Change at C4 D1 (n=99, 114)	-0.6 (2.19)	-0.5 (1.99)
Combined PI: Change at C5 D1 (n=69, 64)	-0.6 (2.46)	-0.6 (2.19)
Combined PI: Change at C6 D1 (n=41, 43)	-0.5 (1.92)	-0.6 (1.89)
Combined PI: Change at C7 D1 (n=25, 27)	-0.1 (1.48)	-0.4 (2.78)
Combined PI: Change at C8 D1 (n=12, 13)	1.0 (2.01)	-0.9 (1.76)
Combined PI: Change at C9 D1 (n=6, 6)	-1.3 (1.51)	-0.8 (1.11)
Combined PI: Change at C10 D1 (n=2, 3)	-1.9 (2.69)	-0.1 (1.44)
Combined PI: Change at C11 D1 (n=1, 1)	0.0 (NA)	1.5 (NA)
Combined PI: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Combined PI: Change at C13 D1 (n=1, 1)	0.0 (NA)	-3.0 (NA)
Combined PI:Change follow-up (n=48, 47)	0.5 (2.34)	0.2 (2.56)
Combined Pain Interference(Pf):Baseline(n=244,243)	3.0 (2.64)	2.8 (2.52)
Combined Pf: Change at C2 D1 (n=191, 194)	-0.5 (2.44)	-0.4 (1.97)
Combined Pf: Change at C3 D1 (n=136,143)	-0.8 (2.99)	-0.5 (2.01)
Combined Pf: Change at C4 D1 (n=98,109)	-0.4 (2.62)	-0.7 (2.12)
Combined Pf: Change at C5 D1 (n=66, 62)	-0.6 (3.18)	-0.6 (2.07)
Combined Pf: Change at C6 D1 (n=41, 41)	-0.4 (2.92)	-0.6 (2.38)
Combined Pf: Change at C7 D1 (n=25, 25)	0.3 (2.32)	-0.5 (2.10)
Combined Pf: Change at C8 D1 (n=12, 12)	0.4 (1.84)	-0.9 (2.15)
Combined Pf: Change at C9 D1 (n=6, 6)	-1.4 (2.69)	0.7 (2.86)
Combined Pf: Change at C10 D1 (n=2, 3)	-0.5 (0.71)	2.1 (2.90)
Combined Pf: Change at C11 D1 (n=1, 1)	0.0 (NA)	1.9 (NA)
Combined Pf: Change at C12 D1 (n=1, 0)	0.0 (NA)	NA (NA)
Combined Pf: Change at C13 D1 (n=1, 1)	0.0 (NA)	-2.7 (NA)
Combined Pf: Change at follow-up (n=47, 45)	0.7 (3.55)	0.3 (3.40)

8. Secondary Outcome

Title	Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile
Description	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time Frame	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Baseline (n=289, 290)	0.665 (0.2709)	0.690 (0.2479)
Change at C2 D1 (n=231, 240)	0.050 (0.2699)	0.020 (0.2033)
Change at C3 D1 (n=171, 178)	0.053 (0.2528)	0.028 (0.2362)
Change at C4 D1 (n=128, 131)	0.010 (0.2730)	0.050 (0.2209)
Change at C5 D1 (n=94, 80)	0.010 (0.2889)	0.044 (0.2092)
Change at C6 D1 (n=57, 57)	0.001 (0.2489)	0.058 (0.2294)
Change at C7 D1 (n=37, 36)	0.049 (0.1891)	0.075 (0.1838)
Change at C8 D1 (n=17, 20)	-0.021 (0.2366)	0.071 (0.2188)
Change at C9 D1 (n=9, 9)	0.049 (0.1878)	0.121 (0.3006)
Change at C10 D1 (n=3, 4)	0.181 (0.2206)	0.208 (0.3034)
Change at C11 D1 (n=1, 1)	0.000 (NA)	0.058 (NA)
Change at C12 D1 (n=1, 0)	0.000 (NA)	NA (NA)
Change at C13 D1 (n=1, 1)	0.000 (NA)	0.470 (NA)
Change at follow-up (n=65, 73)	-0.148 (0.3637)	-0.080 (0.3243)

9. Secondary Outcome

Title	Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score
Description	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time Frame	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal

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 + Gemcitabine	Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.	Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Measure Participants	314	316
Baseline (n= 277, 281)	60.6 (23.67)	62.6 (23.09)
Change at Cycle 2 Day 1 (n= 223, 226)	1.0 (19.64)	-0.4 (20.42)
Change at Cycle 3 Day 1 (n= 161, 171)	2.6 (22.30)	1.1 (20.25)
Change at Cycle 4 Day 1 (n=122, 128)	0.5 (22.38)	3.2 (19.81)
Change at Cycle 5 Day 1 (n= 90, 79)	-0.3 (22.83)	1.9 (19.40)
Change at Cycle 6 Day 1 (n= 56, 56)	1.0 (24.63)	3.7 (21.84)
Change at Cycle 7 Day 1 (n= 36, 35)	2.6 (25.82)	4.1 (22.52)
Change at Cycle 8 Day 1 (n= 16, 19)	3.8 (23.21)	9.6 (28.55)
Change at Cycle 9 Day 1 (n= 9, 9)	22.2 (24.93)	7.7 (20.00)
Change at Cycle 10 Day 1 (n= 3, 4)	20.0 (26.46)	6.3 (24.62)
Change at Cycle 11 Day 1 (n= 1, 1)	0.0 (NA)	30.0 (NA)
Change at Cycle 12 Day 1 (n= 1, 0)	0.0 (NA)	NA (NA)
Change at Cycle 13 Day 1 (n= 1, 1)	0.0 (NA)	36.0 (NA)
Change at follow-up (n= 62, 68)	-6.3 (24.07)	-4.8 (22.79)

10. 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	Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 23 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Same event may appear as both AE and SAE, both distinctly presented. An event may be categorized as SAE in 1 subject, AE in another or one subject may have experienced both serious and nonserious event. A participant randomized for Axitinib+Gemcitabine, received Gemcitabine only and was shifted to Placebo+Gemcitabine group for safety evaluation.
Arm/Group Title	Axitinib + Gemcitabine		Placebo + Gemcitabine
Arm/Group Description	Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.		Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
All Cause Mortality
	Axitinib + Gemcitabine		Placebo + Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Axitinib + Gemcitabine		Placebo + Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/304 (35.5%)		102/309 (33%)
Blood and lymphatic system disorders
Anaemia	1/304 (0.3%)		4/309 (1.3%)
Febrile neutropenia	1/304 (0.3%)		1/309 (0.3%)
Neutropenia	0/304 (0%)		1/309 (0.3%)
Splenic vein thrombosis	0/304 (0%)		1/309 (0.3%)
Thrombocytopenia	2/304 (0.7%)		1/309 (0.3%)
Cardiac disorders
Acute myocardial infarction	1/304 (0.3%)		0/309 (0%)
Angina pectoris	1/304 (0.3%)		0/309 (0%)
Atrial fibrillation	0/304 (0%)		1/309 (0.3%)
Cardiac arrest	0/304 (0%)		1/309 (0.3%)
Cardiac failure	0/304 (0%)		1/309 (0.3%)
Cardiac failure congestive	0/304 (0%)		2/309 (0.6%)
Tachycardia	1/304 (0.3%)		0/309 (0%)
Congenital, familial and genetic disorders
Pyloric stenosis	1/304 (0.3%)		0/309 (0%)
Ear and labyrinth disorders
Deafness	1/304 (0.3%)		0/309 (0%)
Endocrine disorders
Adrenal insufficiency	1/304 (0.3%)		0/309 (0%)
Hypothyroidism	1/304 (0.3%)		0/309 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/304 (0%)		1/309 (0.3%)
Abdominal distension	0/304 (0%)		1/309 (0.3%)
Abdominal pain	14/304 (4.6%)		10/309 (3.2%)
Abdominal pain lower	0/304 (0%)		1/309 (0.3%)
Abdominal pain upper	0/304 (0%)		2/309 (0.6%)
Anal fistula	1/304 (0.3%)		0/309 (0%)
Ascites	0/304 (0%)		1/309 (0.3%)
Colonic obstruction	1/304 (0.3%)		0/309 (0%)
Constipation	1/304 (0.3%)		5/309 (1.6%)
Diarrhoea	2/304 (0.7%)		4/309 (1.3%)
Duodenal obstruction	0/304 (0%)		1/309 (0.3%)
Duodenal ulcer	1/304 (0.3%)		0/309 (0%)
Dysphagia	1/304 (0.3%)		0/309 (0%)
Enterocutaneous fistula	1/304 (0.3%)		0/309 (0%)
Gastrointestinal haemorrhage	2/304 (0.7%)		1/309 (0.3%)
Gastrointestinal perforation	1/304 (0.3%)		0/309 (0%)
Haematemesis	1/304 (0.3%)		1/309 (0.3%)
Ileus	0/304 (0%)		3/309 (1%)
Intestinal fistula	1/304 (0.3%)		0/309 (0%)
Intestinal obstruction	2/304 (0.7%)		1/309 (0.3%)
Intestinal perforation	1/304 (0.3%)		1/309 (0.3%)
Large intestinal obstruction	1/304 (0.3%)		1/309 (0.3%)
Large intestine perforation	0/304 (0%)		1/309 (0.3%)
Melaena	1/304 (0.3%)		0/309 (0%)
Nausea	7/304 (2.3%)		3/309 (1%)
Obstruction gastric	0/304 (0%)		1/309 (0.3%)
Pancreatitis acute	1/304 (0.3%)		0/309 (0%)
Peritonitis	2/304 (0.7%)		1/309 (0.3%)
Rectal haemorrhage	0/304 (0%)		1/309 (0.3%)
Small intestinal haemorrhage	0/304 (0%)		1/309 (0.3%)
Small intestinal perforation	1/304 (0.3%)		0/309 (0%)
Subileus	2/304 (0.7%)		0/309 (0%)
Vomiting	9/304 (3%)		11/309 (3.6%)
General disorders
Asthenia	8/304 (2.6%)		2/309 (0.6%)
Chest pain	1/304 (0.3%)		0/309 (0%)
Complication of device insertion	1/304 (0.3%)		0/309 (0%)
Death	3/304 (1%)		1/309 (0.3%)
Device dislocation	0/304 (0%)		1/309 (0.3%)
Device occlusion	2/304 (0.7%)		2/309 (0.6%)
Disease progression	9/304 (3%)		15/309 (4.9%)
Drug interaction	0/304 (0%)		1/309 (0.3%)
Fatigue	4/304 (1.3%)		0/309 (0%)
General physical health deterioration	2/304 (0.7%)		3/309 (1%)
Generalised oedema	0/304 (0%)		1/309 (0.3%)
Impaired healing	1/304 (0.3%)		0/309 (0%)
Mucosal inflammation	0/304 (0%)		1/309 (0.3%)
Obstruction	1/304 (0.3%)		1/309 (0.3%)
Oedema peripheral	0/304 (0%)		2/309 (0.6%)
Pain	0/304 (0%)		1/309 (0.3%)
Performance status decreased	1/304 (0.3%)		0/309 (0%)
Pyrexia	13/304 (4.3%)		5/309 (1.6%)
Hepatobiliary disorders
Acholia	0/304 (0%)		1/309 (0.3%)
Bile duct obstruction	2/304 (0.7%)		2/309 (0.6%)
Cholangitis	7/304 (2.3%)		3/309 (1%)
Cholecystitis acute	1/304 (0.3%)		0/309 (0%)
Cholestasis	3/304 (1%)		0/309 (0%)
Cytolytic hepatitis	1/304 (0.3%)		0/309 (0%)
Gallbladder necrosis	1/304 (0.3%)		0/309 (0%)
Hepatic function abnormal	1/304 (0.3%)		1/309 (0.3%)
Hyperbilirubinaemia	1/304 (0.3%)		3/309 (1%)
Jaundice	6/304 (2%)		4/309 (1.3%)
Jaundice cholestatic	3/304 (1%)		2/309 (0.6%)
Immune system disorders
Contrast media allergy	0/304 (0%)		1/309 (0.3%)
Infections and infestations
Abdominal abscess	1/304 (0.3%)		0/309 (0%)
Biliary tract infection	2/304 (0.7%)		0/309 (0%)
Cellulitis	0/304 (0%)		2/309 (0.6%)
Cytomegalovirus infection	0/304 (0%)		1/309 (0.3%)
Device related infection	0/304 (0%)		1/309 (0.3%)
Diverticulitis	1/304 (0.3%)		0/309 (0%)
Ear infection	0/304 (0%)		1/309 (0.3%)
Escherichia urinary tract infection	1/304 (0.3%)		0/309 (0%)
Gastroenteritis	1/304 (0.3%)		0/309 (0%)
Infection	1/304 (0.3%)		2/309 (0.6%)
Peritoneal infection	0/304 (0%)		1/309 (0.3%)
Pneumonia	2/304 (0.7%)		4/309 (1.3%)
Respiratory tract infection	0/304 (0%)		1/309 (0.3%)
Sepsis	1/304 (0.3%)		5/309 (1.6%)
Septic shock	1/304 (0.3%)		0/309 (0%)
Urinary tract infection	1/304 (0.3%)		1/309 (0.3%)
Urinary tract infection fungal	1/304 (0.3%)		0/309 (0%)
Urosepsis	1/304 (0.3%)		1/309 (0.3%)
Injury, poisoning and procedural complications
Drug dispensing error	0/304 (0%)		1/309 (0.3%)
Fall	0/304 (0%)		1/309 (0.3%)
Hand fracture	0/304 (0%)		1/309 (0.3%)
Wrist fracture	0/304 (0%)		1/309 (0.3%)
Investigations
Alanine aminotransferase increased	1/304 (0.3%)		0/309 (0%)
Aspartate aminotransferase increased	1/304 (0.3%)		0/309 (0%)
Blood alkaline phosphatase increased	1/304 (0.3%)		0/309 (0%)
Blood bilirubin increased	0/304 (0%)		1/309 (0.3%)
Blood creatinine increased	0/304 (0%)		1/309 (0.3%)
Haemoglobin decreased	1/304 (0.3%)		3/309 (1%)
Liver function test abnormal	1/304 (0.3%)		1/309 (0.3%)
Neutrophil count decreased	1/304 (0.3%)		1/309 (0.3%)
Platelet count decreased	2/304 (0.7%)		1/309 (0.3%)
White blood cell count decreased	1/304 (0.3%)		0/309 (0%)
Metabolism and nutrition disorders
Decreased appetite	7/304 (2.3%)		4/309 (1.3%)
Dehydration	4/304 (1.3%)		4/309 (1.3%)
Diabetes mellitus	0/304 (0%)		1/309 (0.3%)
Hypercalcaemia	1/304 (0.3%)		0/309 (0%)
Hyperglycaemia	1/304 (0.3%)		1/309 (0.3%)
Hypoalbuminaemia	0/304 (0%)		1/309 (0.3%)
Hypoglycaemia	2/304 (0.7%)		0/309 (0%)
Hypokalaemia	4/304 (1.3%)		1/309 (0.3%)
Hyponatraemia	0/304 (0%)		1/309 (0.3%)
Hypophagia	1/304 (0.3%)		0/309 (0%)
Malnutrition	2/304 (0.7%)		0/309 (0%)
Tumour lysis syndrome	0/304 (0%)		1/309 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/304 (0.3%)		0/309 (0%)
Back pain	2/304 (0.7%)		2/309 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Duodenal neoplasm	0/304 (0%)		1/309 (0.3%)
Metastatic neoplasm	1/304 (0.3%)		0/309 (0%)
Neoplasm progression	1/304 (0.3%)		0/309 (0%)
Pancreatic carcinoma	1/304 (0.3%)		1/309 (0.3%)
Tumour associated fever	0/304 (0%)		1/309 (0.3%)
Tumour pain	1/304 (0.3%)		1/309 (0.3%)
Nervous system disorders
Cerebral ischaemia	1/304 (0.3%)		0/309 (0%)
Cerebrovascular accident	1/304 (0.3%)		1/309 (0.3%)
Cognitive disorder	1/304 (0.3%)		0/309 (0%)
Diabetic coma	0/304 (0%)		1/309 (0.3%)
Dysgeusia	1/304 (0.3%)		0/309 (0%)
Grand mal convulsion	1/304 (0.3%)		0/309 (0%)
Psychomotor skills impaired	1/304 (0.3%)		0/309 (0%)
Reversible posterior leukoencephalopathy syndrome	1/304 (0.3%)		0/309 (0%)
Sensory disturbance	2/304 (0.7%)		0/309 (0%)
Somnolence	1/304 (0.3%)		0/309 (0%)
Syncope	0/304 (0%)		1/309 (0.3%)
Thrombotic stroke	0/304 (0%)		1/309 (0.3%)
Transient ischaemic attack	1/304 (0.3%)		1/309 (0.3%)
Psychiatric disorders
Agitation	0/304 (0%)		1/309 (0.3%)
Anxiety	1/304 (0.3%)		0/309 (0%)
Confusional state	4/304 (1.3%)		3/309 (1%)
Depression	1/304 (0.3%)		0/309 (0%)
Mental status changes	1/304 (0.3%)		1/309 (0.3%)
Renal and urinary disorders
Chromaturia	0/304 (0%)		1/309 (0.3%)
Renal failure	3/304 (1%)		1/309 (0.3%)
Renal failure acute	3/304 (1%)		3/309 (1%)
Ureteric perforation	1/304 (0.3%)		0/309 (0%)
Urethral obstruction	0/304 (0%)		1/309 (0.3%)
Urinary incontinence	1/304 (0.3%)		0/309 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/304 (0.7%)		3/309 (1%)
Hiccups	0/304 (0%)		1/309 (0.3%)
Hypoxia	1/304 (0.3%)		1/309 (0.3%)
Interstitial lung disease	0/304 (0%)		2/309 (0.6%)
Pleural effusion	0/304 (0%)		2/309 (0.6%)
Pneumonitis	1/304 (0.3%)		2/309 (0.6%)
Pulmonary embolism	2/304 (0.7%)		6/309 (1.9%)
Respiratory failure	1/304 (0.3%)		0/309 (0%)
Skin and subcutaneous tissue disorders
Erythema	0/304 (0%)		1/309 (0.3%)
Rash	0/304 (0%)		2/309 (0.6%)
Skin ulcer	1/304 (0.3%)		0/309 (0%)
Vascular disorders
Bleeding varicose vein	0/304 (0%)		1/309 (0.3%)
Deep vein thrombosis	1/304 (0.3%)		3/309 (1%)
Hypertension	1/304 (0.3%)		1/309 (0.3%)
Hypotension	1/304 (0.3%)		2/309 (0.6%)
Phlebitis	0/304 (0%)		1/309 (0.3%)
Shock	0/304 (0%)		1/309 (0.3%)
Venous thrombosis	0/304 (0%)		1/309 (0.3%)
Venous thrombosis limb	0/304 (0%)		1/309 (0.3%)
Other (Not Including Serious) Adverse Events
	Axitinib + Gemcitabine		Placebo + Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	276/304 (90.8%)		276/309 (89.3%)
Blood and lymphatic system disorders
Anaemia	25/304 (8.2%)		51/309 (16.5%)
Disseminated intravascular coagulation	1/304 (0.3%)		0/309 (0%)
Eosinopenia	1/304 (0.3%)		0/309 (0%)
Erythroblastosis	0/304 (0%)		1/309 (0.3%)
Erythropenia	0/304 (0%)		1/309 (0.3%)
Granulocytopenia	0/304 (0%)		1/309 (0.3%)
Haemoglobinaemia	1/304 (0.3%)		2/309 (0.6%)
Iron deficiency anaemia	0/304 (0%)		1/309 (0.3%)
Leukocytosis	2/304 (0.7%)		1/309 (0.3%)
Leukopenia	23/304 (7.6%)		13/309 (4.2%)
Lymphadenopathy	1/304 (0.3%)		0/309 (0%)
Lymphocytosis	1/304 (0.3%)		0/309 (0%)
Lymphopenia	1/304 (0.3%)		7/309 (2.3%)
Neutropenia	73/304 (24%)		53/309 (17.2%)
Neutrophilia	1/304 (0.3%)		0/309 (0%)
Thrombocytopenia	48/304 (15.8%)		34/309 (11%)
Thrombocytosis	4/304 (1.3%)		3/309 (1%)
Cardiac disorders
Atrial fibrillation	0/304 (0%)		1/309 (0.3%)
Atrial flutter	0/304 (0%)		1/309 (0.3%)
Bradycardia	0/304 (0%)		2/309 (0.6%)
Bundle branch block right	1/304 (0.3%)		0/309 (0%)
Cardiovascular disorder	1/304 (0.3%)		0/309 (0%)
Cyanosis	0/304 (0%)		1/309 (0.3%)
Diastolic dysfunction	1/304 (0.3%)		0/309 (0%)
Mitral valve incompetence	0/304 (0%)		1/309 (0.3%)
Nodal rhythm	1/304 (0.3%)		0/309 (0%)
Palpitations	4/304 (1.3%)		2/309 (0.6%)
Pericardial effusion	0/304 (0%)		1/309 (0.3%)
Splinter haemorrhages	1/304 (0.3%)		0/309 (0%)
Supraventricular extrasystoles	1/304 (0.3%)		0/309 (0%)
Tachycardia	1/304 (0.3%)		5/309 (1.6%)
Ventricular tachycardia	1/304 (0.3%)		0/309 (0%)
Congenital, familial and genetic disorders
Congenital foot malformation	1/304 (0.3%)		0/309 (0%)
Ear and labyrinth disorders
Auricular perichondritis	1/304 (0.3%)		0/309 (0%)
Cerumen impaction	1/304 (0.3%)		0/309 (0%)
Deafness	0/304 (0%)		1/309 (0.3%)
Ear discomfort	5/304 (1.6%)		1/309 (0.3%)
Ear pain	1/304 (0.3%)		1/309 (0.3%)
Hypoacusis	0/304 (0%)		1/309 (0.3%)
Tinnitus	5/304 (1.6%)		0/309 (0%)
Vertigo	4/304 (1.3%)		5/309 (1.6%)
Endocrine disorders
Hyperthyroidism	2/304 (0.7%)		1/309 (0.3%)
Hypoparathyroidism	1/304 (0.3%)		0/309 (0%)
Hypothyroidism	15/304 (4.9%)		4/309 (1.3%)
Thyroiditis	1/304 (0.3%)		0/309 (0%)
Eye disorders
Asthenopia	0/304 (0%)		1/309 (0.3%)
Conjunctivitis	0/304 (0%)		1/309 (0.3%)
Diplopia	3/304 (1%)		0/309 (0%)
Dry eye	1/304 (0.3%)		1/309 (0.3%)
Eye pruritus	0/304 (0%)		1/309 (0.3%)
Eyelid oedema	1/304 (0.3%)		0/309 (0%)
Lacrimation increased	2/304 (0.7%)		2/309 (0.6%)
Ocular discomfort	0/304 (0%)		1/309 (0.3%)
Ocular hyperaemia	0/304 (0%)		2/309 (0.6%)
Scotoma	0/304 (0%)		1/309 (0.3%)
Vision blurred	1/304 (0.3%)		0/309 (0%)
Visual acuity reduced	1/304 (0.3%)		0/309 (0%)
Gastrointestinal disorders
Abdominal discomfort	3/304 (1%)		5/309 (1.6%)
Abdominal distension	12/304 (3.9%)		12/309 (3.9%)
Abdominal hernia	1/304 (0.3%)		0/309 (0%)
Abdominal mass	1/304 (0.3%)		0/309 (0%)
Abdominal pain	54/304 (17.8%)		52/309 (16.8%)
Abdominal pain lower	2/304 (0.7%)		5/309 (1.6%)
Abdominal pain upper	24/304 (7.9%)		24/309 (7.8%)
Abdominal tenderness	1/304 (0.3%)		0/309 (0%)
Anal haemorrhage	0/304 (0%)		1/309 (0.3%)
Aphthous stomatitis	2/304 (0.7%)		1/309 (0.3%)
Ascites	5/304 (1.6%)		9/309 (2.9%)
Cheilitis	4/304 (1.3%)		1/309 (0.3%)
Colitis	1/304 (0.3%)		0/309 (0%)
Constipation	88/304 (28.9%)		91/309 (29.4%)
Dental caries	0/304 (0%)		1/309 (0.3%)
Diarrhoea	96/304 (31.6%)		64/309 (20.7%)
Dry mouth	14/304 (4.6%)		14/309 (4.5%)
Duodenal obstruction	0/304 (0%)		1/309 (0.3%)
Duodenal ulcer	0/304 (0%)		2/309 (0.6%)
Duodenogastric reflux	0/304 (0%)		1/309 (0.3%)
Dyspepsia	14/304 (4.6%)		22/309 (7.1%)
Dysphagia	7/304 (2.3%)		1/309 (0.3%)
Enteritis	1/304 (0.3%)		0/309 (0%)
Eructation	2/304 (0.7%)		1/309 (0.3%)
Faeces discoloured	1/304 (0.3%)		0/309 (0%)
Faeces pale	1/304 (0.3%)		0/309 (0%)
Flatulence	8/304 (2.6%)		9/309 (2.9%)
Frequent bowel movements	0/304 (0%)		1/309 (0.3%)
Gastritis	2/304 (0.7%)		1/309 (0.3%)
Gastritis erosive	0/304 (0%)		1/309 (0.3%)
Gastrointestinal disorder	1/304 (0.3%)		0/309 (0%)
Gastrointestinal obstruction	0/304 (0%)		1/309 (0.3%)
Gastrooesophageal reflux disease	6/304 (2%)		4/309 (1.3%)
Gingival bleeding	0/304 (0%)		1/309 (0.3%)
Gingival pain	0/304 (0%)		1/309 (0.3%)
Gingival ulceration	1/304 (0.3%)		0/309 (0%)
Gingivitis	6/304 (2%)		1/309 (0.3%)
Glossitis	7/304 (2.3%)		0/309 (0%)
Glossodynia	2/304 (0.7%)		0/309 (0%)
Haematemesis	1/304 (0.3%)		2/309 (0.6%)
Haematochezia	2/304 (0.7%)		0/309 (0%)
Haemorrhoids	4/304 (1.3%)		5/309 (1.6%)
Hiatus hernia	1/304 (0.3%)		0/309 (0%)
Ileus	2/304 (0.7%)		0/309 (0%)
Intestinal obstruction	0/304 (0%)		2/309 (0.6%)
Lip dry	0/304 (0%)		1/309 (0.3%)
Mouth ulceration	2/304 (0.7%)		0/309 (0%)
Nausea	138/304 (45.4%)		112/309 (36.2%)
Odynophagia	2/304 (0.7%)		1/309 (0.3%)
Oesophageal pain	0/304 (0%)		1/309 (0.3%)
Oesophagitis	0/304 (0%)		1/309 (0.3%)
Oral discomfort	1/304 (0.3%)		0/309 (0%)
Oral disorder	0/304 (0%)		1/309 (0.3%)
Oral dysaesthesia	2/304 (0.7%)		1/309 (0.3%)
Oral pain	4/304 (1.3%)		0/309 (0%)
Pancreatic insufficiency	0/304 (0%)		1/309 (0.3%)
Pancreatitis acute	0/304 (0%)		1/309 (0.3%)
Periodontitis	1/304 (0.3%)		0/309 (0%)
Pneumoperitoneum	1/304 (0.3%)		0/309 (0%)
Proctalgia	0/304 (0%)		2/309 (0.6%)
Rectal haemorrhage	2/304 (0.7%)		1/309 (0.3%)
Reflux gastritis	1/304 (0.3%)		1/309 (0.3%)
Reflux oesophagitis	1/304 (0.3%)		1/309 (0.3%)
Regurgitation	1/304 (0.3%)		0/309 (0%)
Retching	3/304 (1%)		0/309 (0%)
Salivary hypersecretion	1/304 (0.3%)		1/309 (0.3%)
Steatorrhoea	2/304 (0.7%)		2/309 (0.6%)
Stomatitis	52/304 (17.1%)		12/309 (3.9%)
Thrombosis mesenteric vessel	0/304 (0%)		1/309 (0.3%)
Toothache	3/304 (1%)		2/309 (0.6%)
Vomiting	91/304 (29.9%)		95/309 (30.7%)
Mass	1/304 (0.3%)		0/309 (0%)
General disorders
Adhesion	0/304 (0%)		1/309 (0.3%)
Asthenia	38/304 (12.5%)		38/309 (12.3%)
Catheter site erythema	0/304 (0%)		2/309 (0.6%)
Catheter site haemorrhage	0/304 (0%)		1/309 (0.3%)
Catheter site pain	0/304 (0%)		2/309 (0.6%)
Catheter site pruritus	0/304 (0%)		1/309 (0.3%)
Chest discomfort	2/304 (0.7%)		2/309 (0.6%)
Chest pain	10/304 (3.3%)		6/309 (1.9%)
Chills	13/304 (4.3%)		11/309 (3.6%)
Device occlusion	0/304 (0%)		1/309 (0.3%)
Early satiety	1/304 (0.3%)		1/309 (0.3%)
Face oedema	1/304 (0.3%)		0/309 (0%)
Fatigue	125/304 (41.1%)		113/309 (36.6%)
Feeling cold	1/304 (0.3%)		1/309 (0.3%)
Feeling hot	0/304 (0%)		1/309 (0.3%)
General physical health deterioration	6/304 (2%)		2/309 (0.6%)
Generalised oedema	0/304 (0%)		1/309 (0.3%)
Hernia pain	0/304 (0%)		1/309 (0.3%)
Hyperthermia	1/304 (0.3%)		1/309 (0.3%)
Influenza like illness	9/304 (3%)		9/309 (2.9%)
Injection site extravasation	1/304 (0.3%)		0/309 (0%)
Injection site reaction	1/304 (0.3%)		2/309 (0.6%)
Malaise	0/304 (0%)		2/309 (0.6%)
Mucosal dryness	2/304 (0.7%)		0/309 (0%)
Mucosal inflammation	34/304 (11.2%)		13/309 (4.2%)
Oedema	6/304 (2%)		5/309 (1.6%)
Oedema peripheral	22/304 (7.2%)		46/309 (14.9%)
Pain	16/304 (5.3%)		7/309 (2.3%)
Performance status decreased	1/304 (0.3%)		0/309 (0%)
Pyrexia	38/304 (12.5%)		44/309 (14.2%)
Thirst	2/304 (0.7%)		1/309 (0.3%)
Thrombosis in device	2/304 (0.7%)		0/309 (0%)
Ulcer	0/304 (0%)		1/309 (0.3%)
Hepatobiliary disorders
Bile duct obstruction	2/304 (0.7%)		1/309 (0.3%)
Cholangitis	4/304 (1.3%)		4/309 (1.3%)
Cholestasis	0/304 (0%)		1/309 (0.3%)
Cytolytic hepatitis	0/304 (0%)		1/309 (0.3%)
Hepatic function abnormal	4/304 (1.3%)		2/309 (0.6%)
Hepatic pain	1/304 (0.3%)		0/309 (0%)
Hepatomegaly	0/304 (0%)		2/309 (0.6%)
Hepatorenal syndrome	0/304 (0%)		1/309 (0.3%)
Hepatotoxicity	6/304 (2%)		1/309 (0.3%)
Hyperbilirubinaemia	6/304 (2%)		9/309 (2.9%)
Jaundice	3/304 (1%)		1/309 (0.3%)
Liver disorder	0/304 (0%)		1/309 (0.3%)
Liver tenderness	1/304 (0.3%)		0/309 (0%)
Portal vein thrombosis	0/304 (0%)		2/309 (0.6%)
Immune system disorders
Contrast media allergy	0/304 (0%)		1/309 (0.3%)
Food allergy	1/304 (0.3%)		0/309 (0%)
Hypersensitivity	2/304 (0.7%)		1/309 (0.3%)
Seasonal allergy	0/304 (0%)		1/309 (0.3%)
Infections and infestations
Abscess	1/304 (0.3%)		0/309 (0%)
Acariasis	0/304 (0%)		1/309 (0.3%)
Arthritis infective	1/304 (0.3%)		0/309 (0%)
Bacterial infection	0/304 (0%)		1/309 (0.3%)
Biliary tract infection	2/304 (0.7%)		1/309 (0.3%)
Bronchitis	3/304 (1%)		1/309 (0.3%)
Candidiasis	2/304 (0.7%)		0/309 (0%)
Catheter site infection	1/304 (0.3%)		2/309 (0.6%)
Cellulitis	3/304 (1%)		4/309 (1.3%)
Cystitis	4/304 (1.3%)		3/309 (1%)
Device related infection	1/304 (0.3%)		1/309 (0.3%)
Enteritis infectious	0/304 (0%)		1/309 (0.3%)
Erysipelas	0/304 (0%)		2/309 (0.6%)
Escherichia infection	1/304 (0.3%)		0/309 (0%)
Eye infection	1/304 (0.3%)		0/309 (0%)
Fungal infection	1/304 (0.3%)		1/309 (0.3%)
Furuncle	1/304 (0.3%)		1/309 (0.3%)
Gastroenteritis	1/304 (0.3%)		2/309 (0.6%)
Infection	4/304 (1.3%)		1/309 (0.3%)
Influenza	1/304 (0.3%)		2/309 (0.6%)
Localised infection	1/304 (0.3%)		0/309 (0%)
Lower respiratory tract infection	1/304 (0.3%)		0/309 (0%)
Lung infection	1/304 (0.3%)		0/309 (0%)
Lymphangitis	0/304 (0%)		1/309 (0.3%)
Nasopharyngitis	9/304 (3%)		7/309 (2.3%)
Oesophageal candidiasis	1/304 (0.3%)		0/309 (0%)
Oral candidiasis	6/304 (2%)		5/309 (1.6%)
Oral fungal infection	1/304 (0.3%)		0/309 (0%)
Oral herpes	3/304 (1%)		1/309 (0.3%)
Oral infection	0/304 (0%)		1/309 (0.3%)
Oropharyngeal candidiasis	0/304 (0%)		1/309 (0.3%)
Perichondritis	0/304 (0%)		1/309 (0.3%)
Pharyngitis	6/304 (2%)		0/309 (0%)
Pharyngotonsillitis	0/304 (0%)		1/309 (0.3%)
Pneumonia	1/304 (0.3%)		1/309 (0.3%)
Pseudomonas infection	1/304 (0.3%)		0/309 (0%)
Respiratory tract infection	1/304 (0.3%)		0/309 (0%)
Rhinitis	1/304 (0.3%)		3/309 (1%)
Sepsis	0/304 (0%)		2/309 (0.6%)
Septic encephalopathy	1/304 (0.3%)		0/309 (0%)
Septic shock	0/304 (0%)		1/309 (0.3%)
Sinusitis	3/304 (1%)		0/309 (0%)
Skin candida	1/304 (0.3%)		0/309 (0%)
Tooth abscess	3/304 (1%)		0/309 (0%)
Tooth infection	1/304 (0.3%)		1/309 (0.3%)
Upper respiratory tract infection	8/304 (2.6%)		2/309 (0.6%)
Urinary tract infection	9/304 (3%)		11/309 (3.6%)
Viral infection	1/304 (0.3%)		0/309 (0%)
Injury, poisoning and procedural complications
Anal injury	2/304 (0.7%)		0/309 (0%)
Arthropod bite	1/304 (0.3%)		0/309 (0%)
Burn oesophageal	1/304 (0.3%)		0/309 (0%)
Contusion	1/304 (0.3%)		2/309 (0.6%)
Drug toxicity	0/304 (0%)		1/309 (0.3%)
Eschar	0/304 (0%)		1/309 (0.3%)
Fall	2/304 (0.7%)		2/309 (0.6%)
Feeding tube complication	0/304 (0%)		1/309 (0.3%)
Humerus fracture	1/304 (0.3%)		0/309 (0%)
Incision site pain	1/304 (0.3%)		0/309 (0%)
Incisional hernia	0/304 (0%)		1/309 (0.3%)
Medication error	1/304 (0.3%)		1/309 (0.3%)
Overdose	1/304 (0.3%)		0/309 (0%)
Post procedural complication	0/304 (0%)		1/309 (0.3%)
Post procedural haematoma	0/304 (0%)		1/309 (0.3%)
Post procedural haemorrhage	1/304 (0.3%)		0/309 (0%)
Postoperative wound complication	1/304 (0.3%)		0/309 (0%)
Procedural pain	0/304 (0%)		1/309 (0.3%)
Skin laceration	0/304 (0%)		1/309 (0.3%)
Spinal compression fracture	0/304 (0%)		1/309 (0.3%)
Wound	0/304 (0%)		2/309 (0.6%)
Wound dehiscence	1/304 (0.3%)		0/309 (0%)
Investigations
Activated partial thromboplastin time prolonged	2/304 (0.7%)		1/309 (0.3%)
Alanine aminotransferase	1/304 (0.3%)		2/309 (0.6%)
Alanine aminotransferase increased	29/304 (9.5%)		24/309 (7.8%)
Ammonia increased	1/304 (0.3%)		0/309 (0%)
Aspartate aminotransferase	1/304 (0.3%)		2/309 (0.6%)
Aspartate aminotransferase increased	24/304 (7.9%)		21/309 (6.8%)
Bacterial test positive	0/304 (0%)		1/309 (0.3%)
Blood albumin decreased	2/304 (0.7%)		1/309 (0.3%)
Blood alkaline phosphatase	1/304 (0.3%)		1/309 (0.3%)
Blood alkaline phosphatase increased	15/304 (4.9%)		11/309 (3.6%)
Blood amylase increased	2/304 (0.7%)		0/309 (0%)
Blood bilirubin	1/304 (0.3%)		1/309 (0.3%)
Blood bilirubin increased	6/304 (2%)		9/309 (2.9%)
Blood creatinine increased	1/304 (0.3%)		5/309 (1.6%)
Blood culture positive	1/304 (0.3%)		0/309 (0%)
Blood fibrinogen increased	1/304 (0.3%)		1/309 (0.3%)
Blood glucose decreased	1/304 (0.3%)		0/309 (0%)
Blood glucose increased	3/304 (1%)		6/309 (1.9%)
Blood lactate dehydrogenase increased	2/304 (0.7%)		1/309 (0.3%)
Blood magnesium decreased	1/304 (0.3%)		0/309 (0%)
Blood potassium decreased	0/304 (0%)		3/309 (1%)
Blood potassium increased	0/304 (0%)		1/309 (0.3%)
Blood pressure increased	3/304 (1%)		0/309 (0%)
Blood sodium decreased	0/304 (0%)		1/309 (0.3%)
Blood thyroid stimulating hormone decreased	2/304 (0.7%)		1/309 (0.3%)
Blood thyroid stimulating hormone increased	16/304 (5.3%)		0/309 (0%)
Blood urea increased	2/304 (0.7%)		0/309 (0%)
Blood urine	0/304 (0%)		1/309 (0.3%)
Blood urine present	0/304 (0%)		1/309 (0.3%)
Body temperature increased	0/304 (0%)		1/309 (0.3%)
C-reactive protein increased	3/304 (1%)		3/309 (1%)
Eastern cooperative oncology group performance status worsened	0/304 (0%)		1/309 (0.3%)
Electrocardiogram QRS complex abnormal	1/304 (0.3%)		0/309 (0%)
Electrocardiogram QT prolonged	1/304 (0.3%)		0/309 (0%)
Fibrin D dimer increased	1/304 (0.3%)		1/309 (0.3%)
Gamma-glutamyltransferase increased	0/304 (0%)		2/309 (0.6%)
Haematocrit decreased	1/304 (0.3%)		0/309 (0%)
Haemoglobin	0/304 (0%)		3/309 (1%)
Haemoglobin decreased	18/304 (5.9%)		26/309 (8.4%)
International normalised ratio increased	1/304 (0.3%)		2/309 (0.6%)
Liver function test abnormal	4/304 (1.3%)		1/309 (0.3%)
Lymph node palpable	1/304 (0.3%)		0/309 (0%)
Lymphocyte count decreased	6/304 (2%)		4/309 (1.3%)
Mean cell volume abnormal	1/304 (0.3%)		0/309 (0%)
Monocyte count decreased	2/304 (0.7%)		0/309 (0%)
Monocyte count increased	0/304 (0%)		1/309 (0.3%)
Monocyte percentage increased	1/304 (0.3%)		0/309 (0%)
Neutrophil count	5/304 (1.6%)		0/309 (0%)
Neutrophil count decreased	31/304 (10.2%)		38/309 (12.3%)
Neutrophil percentage decreased	0/304 (0%)		1/309 (0.3%)
Oxygen saturation decreased	0/304 (0%)		1/309 (0.3%)
Platelet count	4/304 (1.3%)		1/309 (0.3%)
Platelet count decreased	43/304 (14.1%)		40/309 (12.9%)
Platelet count increased	0/304 (0%)		1/309 (0.3%)
Protein total decreased	1/304 (0.3%)		1/309 (0.3%)
Protein urine	1/304 (0.3%)		2/309 (0.6%)
Protein urine present	1/304 (0.3%)		0/309 (0%)
Prothrombin time abnormal	0/304 (0%)		1/309 (0.3%)
Prothrombin time prolonged	0/304 (0%)		2/309 (0.6%)
Prothrombin time shortened	0/304 (0%)		1/309 (0.3%)
Red blood cell count decreased	1/304 (0.3%)		0/309 (0%)
Red cell distribution width increased	1/304 (0.3%)		0/309 (0%)
Thyroxine free increased	1/304 (0.3%)		1/309 (0.3%)
Transaminases increased	1/304 (0.3%)		0/309 (0%)
Tri-iodothyronine free decreased	0/304 (0%)		1/309 (0.3%)
Tri-iodothyronine free increased	1/304 (0.3%)		0/309 (0%)
Urine output decreased	1/304 (0.3%)		0/309 (0%)
Weight decreased	44/304 (14.5%)		29/309 (9.4%)
Weight increased	0/304 (0%)		2/309 (0.6%)
White blood cell count	2/304 (0.7%)		1/309 (0.3%)
White blood cell count decreased	20/304 (6.6%)		16/309 (5.2%)
Metabolism and nutrition disorders
Decreased appetite	115/304 (37.8%)		87/309 (28.2%)
Dehydration	5/304 (1.6%)		12/309 (3.9%)
Diabetes mellitus	1/304 (0.3%)		1/309 (0.3%)
Fluid overload	0/304 (0%)		2/309 (0.6%)
Gout	3/304 (1%)		1/309 (0.3%)
Hyperammonaemia	1/304 (0.3%)		0/309 (0%)
Hypercalcaemia	0/304 (0%)		1/309 (0.3%)
Hyperglycaemia	9/304 (3%)		5/309 (1.6%)
Hyperkalaemia	0/304 (0%)		3/309 (1%)
Hyperlipasaemia	1/304 (0.3%)		0/309 (0%)
Hypernatraemia	0/304 (0%)		1/309 (0.3%)
Hyperuricaemia	0/304 (0%)		1/309 (0.3%)
Hypoalbuminaemia	4/304 (1.3%)		5/309 (1.6%)
Hypocalcaemia	1/304 (0.3%)		4/309 (1.3%)
Hypoglycaemia	2/304 (0.7%)		3/309 (1%)
Hypokalaemia	13/304 (4.3%)		8/309 (2.6%)
Hypomagnesaemia	0/304 (0%)		2/309 (0.6%)
Hyponatraemia	4/304 (1.3%)		6/309 (1.9%)
Hypophosphataemia	0/304 (0%)		2/309 (0.6%)
Hypoproteinaemia	1/304 (0.3%)		0/309 (0%)
Lactic acidosis	1/304 (0.3%)		0/309 (0%)
Malnutrition	2/304 (0.7%)		2/309 (0.6%)
Metabolic acidosis	0/304 (0%)		1/309 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/304 (3.3%)		11/309 (3.6%)
Back pain	34/304 (11.2%)		30/309 (9.7%)
Bone pain	3/304 (1%)		2/309 (0.6%)
Bone swelling	0/304 (0%)		1/309 (0.3%)
Flank pain	2/304 (0.7%)		5/309 (1.6%)
Gouty arthritis	0/304 (0%)		1/309 (0.3%)
Intervertebral disc degeneration	0/304 (0%)		1/309 (0.3%)
Joint swelling	0/304 (0%)		4/309 (1.3%)
Muscle contracture	1/304 (0.3%)		2/309 (0.6%)
Muscle spasms	7/304 (2.3%)		3/309 (1%)
Muscle twitching	1/304 (0.3%)		0/309 (0%)
Muscular weakness	4/304 (1.3%)		3/309 (1%)
Musculoskeletal chest pain	2/304 (0.7%)		7/309 (2.3%)
Musculoskeletal discomfort	1/304 (0.3%)		1/309 (0.3%)
Musculoskeletal pain	13/304 (4.3%)		7/309 (2.3%)
Musculoskeletal stiffness	1/304 (0.3%)		1/309 (0.3%)
Myalgia	11/304 (3.6%)		14/309 (4.5%)
Neck pain	1/304 (0.3%)		1/309 (0.3%)
Osteoarthritis	1/304 (0.3%)		0/309 (0%)
Pain in extremity	8/304 (2.6%)		11/309 (3.6%)
Pain in jaw	1/304 (0.3%)		0/309 (0%)
Synovial cyst	0/304 (0%)		1/309 (0.3%)
Torticollis	0/304 (0%)		1/309 (0.3%)
Trigger finger	1/304 (0.3%)		0/309 (0%)
Upper extremity mass	0/304 (0%)		1/309 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	8/304 (2.6%)		4/309 (1.3%)
Tumour associated fever	0/304 (0%)		1/309 (0.3%)
Tumour pain	2/304 (0.7%)		2/309 (0.6%)
Nervous system disorders
Ageusia	0/304 (0%)		2/309 (0.6%)
Amnesia	3/304 (1%)		2/309 (0.6%)
Anaesthesia	1/304 (0.3%)		0/309 (0%)
Aphasia	1/304 (0.3%)		0/309 (0%)
Aphonia	1/304 (0.3%)		0/309 (0%)
Cognitive disorder	1/304 (0.3%)		0/309 (0%)
Cranial nerve disorder	1/304 (0.3%)		0/309 (0%)
Dizziness	10/304 (3.3%)		17/309 (5.5%)
Dysaesthesia	0/304 (0%)		1/309 (0.3%)
Dysarthria	0/304 (0%)		1/309 (0.3%)
Dysgeusia	25/304 (8.2%)		14/309 (4.5%)
Extrapyramidal disorder	0/304 (0%)		1/309 (0.3%)
Headache	45/304 (14.8%)		26/309 (8.4%)
Hyperaesthesia	0/304 (0%)		1/309 (0.3%)
Hypersomnia	0/304 (0%)		1/309 (0.3%)
Hypoaesthesia	6/304 (2%)		2/309 (0.6%)
Lethargy	8/304 (2.6%)		12/309 (3.9%)
Loss of consciousness	0/304 (0%)		1/309 (0.3%)
Memory impairment	1/304 (0.3%)		1/309 (0.3%)
Metabolic encephalopathy	1/304 (0.3%)		0/309 (0%)
Migraine	1/304 (0.3%)		0/309 (0%)
Myoclonus	1/304 (0.3%)		0/309 (0%)
Neuropathy peripheral	3/304 (1%)		1/309 (0.3%)
Paraesthesia	4/304 (1.3%)		4/309 (1.3%)
Peripheral sensory neuropathy	3/304 (1%)		7/309 (2.3%)
Polyneuropathy	1/304 (0.3%)		0/309 (0%)
Poor quality sleep	1/304 (0.3%)		0/309 (0%)
Sciatica	1/304 (0.3%)		1/309 (0.3%)
Sinus headache	0/304 (0%)		1/309 (0.3%)
Somnolence	2/304 (0.7%)		1/309 (0.3%)
Syncope	2/304 (0.7%)		1/309 (0.3%)
Tremor	3/304 (1%)		1/309 (0.3%)
Psychiatric disorders
Agitation	0/304 (0%)		1/309 (0.3%)
Anxiety	16/304 (5.3%)		19/309 (6.1%)
Aversion	3/304 (1%)		0/309 (0%)
Confusional state	7/304 (2.3%)		3/309 (1%)
Decreased activity	0/304 (0%)		1/309 (0.3%)
Delirium	3/304 (1%)		0/309 (0%)
Depression	14/304 (4.6%)		10/309 (3.2%)
Dysphoria	1/304 (0.3%)		0/309 (0%)
Hallucination	2/304 (0.7%)		3/309 (1%)
Hallucinations, mixed	0/304 (0%)		1/309 (0.3%)
Insomnia	25/304 (8.2%)		18/309 (5.8%)
Loss of libido	1/304 (0.3%)		0/309 (0%)
Nightmare	1/304 (0.3%)		0/309 (0%)
Paranoia	1/304 (0.3%)		0/309 (0%)
Sleep disorder	1/304 (0.3%)		0/309 (0%)
Vomiting psychogenic	0/304 (0%)		1/309 (0.3%)
Renal and urinary disorders
Bladder pain	1/304 (0.3%)		0/309 (0%)
Chromaturia	1/304 (0.3%)		0/309 (0%)
Dysuria	5/304 (1.6%)		1/309 (0.3%)
Haematuria	4/304 (1.3%)		4/309 (1.3%)
Hydronephrosis	1/304 (0.3%)		0/309 (0%)
Micturition urgency	0/304 (0%)		1/309 (0.3%)
Pollakiuria	4/304 (1.3%)		3/309 (1%)
Polyuria	0/304 (0%)		1/309 (0.3%)
Proteinuria	17/304 (5.6%)		12/309 (3.9%)
Pyuria	0/304 (0%)		1/309 (0.3%)
Renal failure acute	0/304 (0%)		1/309 (0.3%)
Renal impairment	1/304 (0.3%)		0/309 (0%)
Urethral pain	0/304 (0%)		1/309 (0.3%)
Urinary incontinence	0/304 (0%)		2/309 (0.6%)
Reproductive system and breast disorders
Breast enlargement	0/304 (0%)		1/309 (0.3%)
Genital haemorrhage	0/304 (0%)		1/309 (0.3%)
Menopausal symptoms	1/304 (0.3%)		0/309 (0%)
Metrorrhagia	1/304 (0.3%)		0/309 (0%)
Prostatism	0/304 (0%)		1/309 (0.3%)
Pruritus genital	1/304 (0.3%)		0/309 (0%)
Scrotal ulcer	1/304 (0.3%)		0/309 (0%)
Vaginal haemorrhage	0/304 (0%)		1/309 (0.3%)
Vulvovaginal dryness	2/304 (0.7%)		0/309 (0%)
Vulvovaginal pruritus	0/304 (0%)		1/309 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asphyxia	1/304 (0.3%)		0/309 (0%)
Asthma	0/304 (0%)		2/309 (0.6%)
Atelectasis	1/304 (0.3%)		1/309 (0.3%)
Cough	24/304 (7.9%)		19/309 (6.1%)
Dry throat	1/304 (0.3%)		0/309 (0%)
Dysphonia	68/304 (22.4%)		12/309 (3.9%)
Dyspnoea	24/304 (7.9%)		20/309 (6.5%)
Dyspnoea exertional	1/304 (0.3%)		2/309 (0.6%)
Epistaxis	14/304 (4.6%)		7/309 (2.3%)
Haemoptysis	2/304 (0.7%)		0/309 (0%)
Hiccups	6/304 (2%)		3/309 (1%)
Hypoxia	1/304 (0.3%)		3/309 (1%)
Interstitial lung disease	1/304 (0.3%)		0/309 (0%)
Laryngeal oedema	1/304 (0.3%)		0/309 (0%)
Nasal congestion	2/304 (0.7%)		1/309 (0.3%)
Nasal dryness	1/304 (0.3%)		0/309 (0%)
Nasal mucosal disorder	1/304 (0.3%)		0/309 (0%)
Nasal ulcer	1/304 (0.3%)		0/309 (0%)
Oropharyngeal discomfort	0/304 (0%)		1/309 (0.3%)
Oropharyngeal pain	12/304 (3.9%)		1/309 (0.3%)
Painful respiration	0/304 (0%)		1/309 (0.3%)
Pharyngeal oedema	0/304 (0%)		1/309 (0.3%)
Pleural effusion	0/304 (0%)		6/309 (1.9%)
Pneumothorax	0/304 (0%)		1/309 (0.3%)
Productive cough	3/304 (1%)		2/309 (0.6%)
Pulmonary congestion	0/304 (0%)		1/309 (0.3%)
Pulmonary embolism	1/304 (0.3%)		1/309 (0.3%)
Pulmonary hypertension	0/304 (0%)		1/309 (0.3%)
Pulmonary oedema	0/304 (0%)		1/309 (0.3%)
Rales	1/304 (0.3%)		1/309 (0.3%)
Rhinalgia	1/304 (0.3%)		0/309 (0%)
Rhinitis allergic	2/304 (0.7%)		0/309 (0%)
Rhinorrhoea	4/304 (1.3%)		2/309 (0.6%)
Sinus congestion	0/304 (0%)		1/309 (0.3%)
Sputum increased	1/304 (0.3%)		0/309 (0%)
Upper-airway cough syndrome	0/304 (0%)		1/309 (0.3%)
Wheezing	1/304 (0.3%)		0/309 (0%)
Skin and subcutaneous tissue disorders
Acne	4/304 (1.3%)		1/309 (0.3%)
Alopecia	31/304 (10.2%)		20/309 (6.5%)
Circumoral oedema	0/304 (0%)		1/309 (0.3%)
Cold sweat	1/304 (0.3%)		1/309 (0.3%)
Decubitus ulcer	1/304 (0.3%)		1/309 (0.3%)
Dermatitis	3/304 (1%)		0/309 (0%)
Dermatitis acneiform	4/304 (1.3%)		0/309 (0%)
Dermatitis allergic	1/304 (0.3%)		0/309 (0%)
Dermatitis contact	1/304 (0.3%)		0/309 (0%)
Dry skin	7/304 (2.3%)		2/309 (0.6%)
Eczema	1/304 (0.3%)		2/309 (0.6%)
Erythema	3/304 (1%)		5/309 (1.6%)
Hair texture abnormal	1/304 (0.3%)		0/309 (0%)
Heat rash	1/304 (0.3%)		0/309 (0%)
Hyperhidrosis	3/304 (1%)		3/309 (1%)
Increased tendency to bruise	1/304 (0.3%)		1/309 (0.3%)
Nail bed bleeding	1/304 (0.3%)		0/309 (0%)
Nail bed inflammation	1/304 (0.3%)		0/309 (0%)
Nail disorder	5/304 (1.6%)		1/309 (0.3%)
Night sweats	3/304 (1%)		9/309 (2.9%)
Pain of skin	0/304 (0%)		1/309 (0.3%)
Palmar-plantar erythrodysaesthesia syndrome	18/304 (5.9%)		2/309 (0.6%)
Petechiae	1/304 (0.3%)		1/309 (0.3%)
Pigmentation disorder	1/304 (0.3%)		0/309 (0%)
Pruritus	14/304 (4.6%)		17/309 (5.5%)
Pruritus generalised	0/304 (0%)		1/309 (0.3%)
Rash	43/304 (14.1%)		41/309 (13.3%)
Rash erythematous	3/304 (1%)		0/309 (0%)
Rash generalised	0/304 (0%)		1/309 (0.3%)
Rash macular	1/304 (0.3%)		3/309 (1%)
Rash papular	2/304 (0.7%)		1/309 (0.3%)
Rash pruritic	1/304 (0.3%)		4/309 (1.3%)
Scab	1/304 (0.3%)		0/309 (0%)
Skin exfoliation	1/304 (0.3%)		0/309 (0%)
Skin fissures	2/304 (0.7%)		0/309 (0%)
Skin hyperpigmentation	3/304 (1%)		2/309 (0.6%)
Skin induration	0/304 (0%)		1/309 (0.3%)
Skin irritation	0/304 (0%)		1/309 (0.3%)
Skin lesion	1/304 (0.3%)		2/309 (0.6%)
Skin nodule	0/304 (0%)		1/309 (0.3%)
Skin reaction	10/304 (3.3%)		1/309 (0.3%)
Skin toxicity	1/304 (0.3%)		1/309 (0.3%)
Subcutaneous nodule	1/304 (0.3%)		0/309 (0%)
Swelling face	1/304 (0.3%)		0/309 (0%)
Urticaria	4/304 (1.3%)		1/309 (0.3%)
Surgical and medical procedures
Abdominal cavity drainage	1/304 (0.3%)		0/309 (0%)
Vascular disorders
Angiopathy	1/304 (0.3%)		2/309 (0.6%)
Deep vein thrombosis	4/304 (1.3%)		9/309 (2.9%)
Flushing	1/304 (0.3%)		0/309 (0%)
Haemorrhage	1/304 (0.3%)		1/309 (0.3%)
Hot flush	5/304 (1.6%)		1/309 (0.3%)
Hypertension	84/304 (27.6%)		26/309 (8.4%)
Hypotension	9/304 (3%)		14/309 (4.5%)
Orthostatic hypotension	2/304 (0.7%)		0/309 (0%)
Pallor	1/304 (0.3%)		0/309 (0%)
Phlebitis	2/304 (0.7%)		5/309 (1.6%)
Phlebitis superficial	0/304 (0%)		1/309 (0.3%)
Thrombophlebitis	0/304 (0%)		3/309 (1%)
Thrombophlebitis superficial	0/304 (0%)		1/309 (0.3%)
Thrombosis	2/304 (0.7%)		3/309 (1%)
Vein pain	0/304 (0%)		1/309 (0.3%)
Venous thrombosis	1/304 (0.3%)		0/309 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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