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

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ClinicalTrials.gov Identifier: NCT00471146
Recruitment Status : Completed
First Posted : May 9, 2007
Results First Posted : July 16, 2012
Last Update Posted : July 16, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Carcinoma, Pancreatic Ductal
Interventions Drug: AG-013736
Drug: Gemcitabine
Drug: placebo
Enrollment 630
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Axitinib + Gemcitabine Placebo + Gemcitabine
Hide 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
Reason Not Completed
Adverse Event             32             33
Withdrawal by Subject             14             11
Death             11             12
Lost to Follow-up             4             2
Protocol Violation             2             2
Objective progression or relapse             84             87
Global deterioration of health status             12             14
Randomized but not treated             9             8
Other             4             5
Arm/Group Title Axitinib + Gemcitabine Placebo + Gemcitabine Total
Hide 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 Number of Baseline Participants 314 316 630
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 314 participants 316 participants 630 participants
Less than 65 years 203 179 382
Greater than or equal to 65 years 111 137 248
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 316 participants 630 participants
Female
123
  39.2%
128
  40.5%
251
  39.8%
Male
191
  60.8%
188
  59.5%
379
  60.2%
1.Primary Outcome
Title Overall Survival (OS)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Median (95% Confidence Interval)
Unit of Measure: Weeks
36.9
(30.1 to 41.1)
35.8
(30.0 to 44.8)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.014
Confidence Interval (2-Sided) 95%
0.786 to 1.309
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Median (95% Confidence Interval)
Unit of Measure: Weeks
19.1
(17.1 to 24.4)
18.9
(16.2 to 22.6)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.006
Confidence Interval (2-Sided) 95%
0.779 to 1.298
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Objective Response (OR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
4.9
(2.5 to 8.3)
1.6
(0.4 to 4.0)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
1.0 to 10.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response (DR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 12 4
Median (95% Confidence Interval)
Unit of Measure: Weeks
33.1
(16.1 to 33.1)
NA [1] 
(NA to NA)
[1]
Median duration of response for placebo+gemcitabine arm did not reach at the time of data cut-off.
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Mean (Standard Deviation)
Unit of Measure: Units on a scale
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 [1]   (NA) -6.600 [1]   (NA)
Physical functioning: Change at C12 D1 (n=1, 0) 0.000 [1]   (NA) NA [2]   (NA)
Physical functioning: Change at C13 D1 (n=1, 0) 0.000 [1]   (NA) NA [2]   (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 [1]   (NA) -50.0 [1]   (NA)
Role functioning: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Role functioning: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) -16.6 [1]   (NA)
EF: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
EF: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
CF: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
CF: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 33.4 [1]   (NA)
Social functioning: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Social functioning: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 11.1 [1]   (NA)
Fatigue: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Fatigue: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
Nausea and vomiting: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Nausea and vomiting: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) -33.3 [1]   (NA)
Pain: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Pain: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
Dyspnoea: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Dyspnoea: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 33.3 [1]   (NA)
Insomnia: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Insomnia: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 33.3 [1]   (NA)
Loss of appetite: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Loss of appetite: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) -66.7 [1]   (NA)
Constipation: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Constipation: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
Diarrhoea: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Diarrhoea: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 66.7 [1]   (NA)
FD: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
FD: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
GHS/QoL: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
GHS/QoL: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
GHS/QoL:Change at follow-up (n=65, 71) -9.1  (26.06) -6.7  (24.50)
[1]
Standard deviation was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Mean (Standard Deviation)
Unit of Measure: Units on a scale
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 [1]   (NA) 0.0 [1]   (NA)
Pancreatic Pain: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Pancreatic Pain: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
Hepatic: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Hepatic: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 66.7 [1]   (NA)
Digestive Symptom: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Digestive Symptom: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [2]   (NA) 11.1  (19.28)
Sexuality: Change at C11 D1 (n=0, 1) NA [2]   (NA) 33.3 [1]   (NA)
Sexuality: Change at C12 D1 (n=0, 0) NA [2]   (NA) NA [2]   (NA)
Sexuality: Change at C13 D1 (n=0, 0) NA [2]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
HC satisfaction: Change at C12 D1 (n=1, 0) -33.3 [1]   (NA) NA [2]   (NA)
HC satisfaction: Change at C13 D1(n=1, 0) -33.3 [1]   (NA) NA [2]   (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 [1]   (NA) -50.0 [1]   (NA)
Body Image: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Body Image: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) -100.0 [1]   (NA)
Altered Bowel Habit: Change at C12 D1 (n=1, 0) 16.7 [1]   (NA) NA [2]   (NA)
Altered Bowel Habit: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 33.3 [1]   (NA)
Ascites: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Ascites: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
Indigestion: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Indigestion: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) -11.1  (19.23)
Flatulence: Change at C11 D1 (n=0, 1) NA [2]   (NA) 0.0 [1]   (NA)
Flatulence: Change at C12 D1 (n=0, 0) NA [2]   (NA) NA [2]   (NA)
Flatulence: Change at C13 D1 (n=0, 0) NA [2]   (NA) NA [2]   (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 [1]   (NA) 0.0  (28.87)
Cachexia: Change at C11 D1 (n=0, 1) NA [2]   (NA) -16.6 [1]   (NA)
Cachexia: Change at C12 D1 (n=0, 0) NA [2]   (NA) NA [2]   (NA)
Cachexia: Change at C13 D1 (n=0, 0) NA [2]   (NA) NA [2]   (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 [2]   (NA) 0.0  (40.12)
Side Effects: Change at C11 D1 (n=0, 1) NA [2]   (NA) -33.4 [1]   (NA)
Side Effects: Change at C12 D1 (n=0, 0) NA [2]   (NA) NA [2]   (NA)
Side Effects: Change at C13 D1 (n=0, 0) NA [2]   (NA) NA [2]   (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 [1]   (NA) 0.0 [1]   (NA)
Fear of FH: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Fear of FH: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (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 [1]   (NA) -11.1  (69.43)
Future Plan ability: Change at C11 D1 (n=1, 1) 0.0 [1]   (NA) -66.7 [1]   (NA)
Future Plan ability: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Future Plan ability: Change at C13 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Future Plan ability: Change at followup (n=48, 45) 21.5  (35.40) 5.2  (38.25)
[1]
Standard deviation was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
7.Secondary Outcome
Title Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Mean (Standard Deviation)
Unit of Measure: Units on a scale
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 [1]   (NA) 0.0 [1]   (NA)
Worst Pain: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Worst Pain: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -4.0 [1]   (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 [1]   (NA) 4.0 [1]   (NA)
Pain in Last 24 hrs: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Pain in Last 24 hrs: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -1.0 [1]   (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 [1]   (NA) -3.0 [1]   (NA)
Pain on the Average: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Pain on the Average: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -2.0 [1]   (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 [1]   (NA) 5.0 [1]   (NA)
Pain Right Now: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Pain Right Now: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -5.0 [1]   (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 [1]   (NA) 0.0  (1.41)
Relief Pain Tx: Change at C11 D1 (n=0, 1) NA [2]   (NA) 0.0 [1]   (NA)
Relief Pain Tx: Change at C12 D1 (n=0, 0) NA [2]   (NA) NA [2]   (NA)
Relief Pain Tx: Change at C13 D1 (n=0, 0) NA [2]   (NA) NA [2]   (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 [1]   (NA) 1.0 [1]   (NA)
General Activity: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
General Activity: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -1.0 [1]   (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 [1]   (NA) 5.0 [1]   (NA)
Mood: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Mood: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -3.0 [1]   (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 [1]   (NA) 0.0 [1]   (NA)
Walking Ability: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Walking Ability: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -2.0 [1]   (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 [1]   (NA) 2.0 [1]   (NA)
Normal Work: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Normal Work: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -2.0 [1]   (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 [1]   (NA) 2.0 [1]   (NA)
Relations: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Relations: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -2.0 [1]   (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 [1]   (NA) 4.0 [1]   (NA)
Sleep: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Sleep: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -5.0 [1]   (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 [1]   (NA) -1.0 [1]   (NA)
Enjoyment of Life: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Enjoyment of Life: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -4.0 [1]   (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 [1]   (NA) 1.5 [1]   (NA)
Combined PI: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Combined PI: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -3.0 [1]   (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 [1]   (NA) 1.9 [1]   (NA)
Combined Pf: Change at C12 D1 (n=1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Combined Pf: Change at C13 D1 (n=1, 1) 0.0 [1]   (NA) -2.7 [1]   (NA)
Combined Pf: Change at follow-up (n=47, 45) 0.7  (3.55) 0.3  (3.40)
[1]
Standard deviation was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
8.Secondary Outcome
Title Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Mean (Standard Deviation)
Unit of Measure: Units on a scale
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 [1]   (NA) 0.058 [1]   (NA)
Change at C12 D1 (n=1, 0) 0.000 [1]   (NA) NA [2]   (NA)
Change at C13 D1 (n=1, 1) 0.000 [1]   (NA) 0.470 [1]   (NA)
Change at follow-up (n=65, 73) -0.148  (0.3637) -0.080  (0.3243)
[1]
Standard deviation was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
9.Secondary Outcome
Title Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 314 316
Mean (Standard Deviation)
Unit of Measure: Millimeter (mm)
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 [1]   (NA) 30.0 [1]   (NA)
Change at Cycle 12 Day 1 (n= 1, 0) 0.0 [1]   (NA) NA [2]   (NA)
Change at Cycle 13 Day 1 (n= 1, 1) 0.0 [1]   (NA) 36.0 [1]   (NA)
Change at follow-up (n= 62, 68) -6.3  (24.07) -4.8  (22.79)
[1]
Standard deviation was not estimable since only one participant was evaluable.
[2]
Data was not analyzed as no participants were evaluable for the particular cycle.
10.Secondary Outcome
Title Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)
Hide 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 Not Reported
Time Frame [Not Specified]
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
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Axitinib + Gemcitabine Placebo + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   108/304 (35.53%)   102/309 (33.01%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/304 (0.33%)  4/309 (1.29%) 
Febrile neutropenia * 1  1/304 (0.33%)  1/309 (0.32%) 
Neutropenia * 1  0/304 (0.00%)  1/309 (0.32%) 
Splenic vein thrombosis * 1  0/304 (0.00%)  1/309 (0.32%) 
Thrombocytopenia * 1  2/304 (0.66%)  1/309 (0.32%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/304 (0.33%)  0/309 (0.00%) 
Angina pectoris * 1  1/304 (0.33%)  0/309 (0.00%) 
Atrial fibrillation * 1  0/304 (0.00%)  1/309 (0.32%) 
Cardiac arrest * 1  0/304 (0.00%)  1/309 (0.32%) 
Cardiac failure * 1  0/304 (0.00%)  1/309 (0.32%) 
Cardiac failure congestive * 1  0/304 (0.00%)  2/309 (0.65%) 
Tachycardia * 1  1/304 (0.33%)  0/309 (0.00%) 
Congenital, familial and genetic disorders     
Pyloric stenosis * 1  1/304 (0.33%)  0/309 (0.00%) 
Ear and labyrinth disorders     
Deafness * 1  1/304 (0.33%)  0/309 (0.00%) 
Endocrine disorders     
Adrenal insufficiency * 1  1/304 (0.33%)  0/309 (0.00%) 
Hypothyroidism * 1  1/304 (0.33%)  0/309 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  0/304 (0.00%)  1/309 (0.32%) 
Abdominal distension * 1  0/304 (0.00%)  1/309 (0.32%) 
Abdominal pain * 1  14/304 (4.61%)  10/309 (3.24%) 
Abdominal pain lower * 1  0/304 (0.00%)  1/309 (0.32%) 
Abdominal pain upper * 1  0/304 (0.00%)  2/309 (0.65%) 
Anal fistula * 1  1/304 (0.33%)  0/309 (0.00%) 
Ascites * 1  0/304 (0.00%)  1/309 (0.32%) 
Colonic obstruction * 1  1/304 (0.33%)  0/309 (0.00%) 
Constipation * 1  1/304 (0.33%)  5/309 (1.62%) 
Diarrhoea * 1  2/304 (0.66%)  4/309 (1.29%) 
Duodenal obstruction * 1  0/304 (0.00%)  1/309 (0.32%) 
Duodenal ulcer * 1  1/304 (0.33%)  0/309 (0.00%) 
Dysphagia * 1  1/304 (0.33%)  0/309 (0.00%) 
Enterocutaneous fistula * 1  1/304 (0.33%)  0/309 (0.00%) 
Gastrointestinal haemorrhage * 1  2/304 (0.66%)  1/309 (0.32%) 
Gastrointestinal perforation * 1  1/304 (0.33%)  0/309 (0.00%) 
Haematemesis * 1  1/304 (0.33%)  1/309 (0.32%) 
Ileus * 1  0/304 (0.00%)  3/309 (0.97%) 
Intestinal fistula * 1  1/304 (0.33%)  0/309 (0.00%) 
Intestinal obstruction * 1  2/304 (0.66%)  1/309 (0.32%) 
Intestinal perforation * 1  1/304 (0.33%)  1/309 (0.32%) 
Large intestinal obstruction * 1  1/304 (0.33%)  1/309 (0.32%) 
Large intestine perforation * 1  0/304 (0.00%)  1/309 (0.32%) 
Melaena * 1  1/304 (0.33%)  0/309 (0.00%) 
Nausea * 1  7/304 (2.30%)  3/309 (0.97%) 
Obstruction gastric * 1  0/304 (0.00%)  1/309 (0.32%) 
Pancreatitis acute * 1  1/304 (0.33%)  0/309 (0.00%) 
Peritonitis * 1  2/304 (0.66%)  1/309 (0.32%) 
Rectal haemorrhage * 1  0/304 (0.00%)  1/309 (0.32%) 
Small intestinal haemorrhage * 1  0/304 (0.00%)  1/309 (0.32%) 
Small intestinal perforation * 1  1/304 (0.33%)  0/309 (0.00%) 
Subileus * 1  2/304 (0.66%)  0/309 (0.00%) 
Vomiting * 1  9/304 (2.96%)  11/309 (3.56%) 
General disorders     
Asthenia * 1  8/304 (2.63%)  2/309 (0.65%) 
Chest pain * 1  1/304 (0.33%)  0/309 (0.00%) 
Complication of device insertion * 1  1/304 (0.33%)  0/309 (0.00%) 
Death * 1  3/304 (0.99%)  1/309 (0.32%) 
Device dislocation * 1  0/304 (0.00%)  1/309 (0.32%) 
Device occlusion * 1  2/304 (0.66%)  2/309 (0.65%) 
Disease progression * 1  9/304 (2.96%)  15/309 (4.85%) 
Drug interaction * 1  0/304 (0.00%)  1/309 (0.32%) 
Fatigue * 1  4/304 (1.32%)  0/309 (0.00%) 
General physical health deterioration * 1  2/304 (0.66%)  3/309 (0.97%) 
Generalised oedema * 1  0/304 (0.00%)  1/309 (0.32%) 
Impaired healing * 1  1/304 (0.33%)  0/309 (0.00%) 
Mucosal inflammation * 1  0/304 (0.00%)  1/309 (0.32%) 
Obstruction * 1  1/304 (0.33%)  1/309 (0.32%) 
Oedema peripheral * 1  0/304 (0.00%)  2/309 (0.65%) 
Pain * 1  0/304 (0.00%)  1/309 (0.32%) 
Performance status decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Pyrexia * 1  13/304 (4.28%)  5/309 (1.62%) 
Hepatobiliary disorders     
Acholia * 1  0/304 (0.00%)  1/309 (0.32%) 
Bile duct obstruction * 1  2/304 (0.66%)  2/309 (0.65%) 
Cholangitis * 1  7/304 (2.30%)  3/309 (0.97%) 
Cholecystitis acute * 1  1/304 (0.33%)  0/309 (0.00%) 
Cholestasis * 1  3/304 (0.99%)  0/309 (0.00%) 
Cytolytic hepatitis * 1  1/304 (0.33%)  0/309 (0.00%) 
Gallbladder necrosis * 1  1/304 (0.33%)  0/309 (0.00%) 
Hepatic function abnormal * 1  1/304 (0.33%)  1/309 (0.32%) 
Hyperbilirubinaemia * 1  1/304 (0.33%)  3/309 (0.97%) 
Jaundice * 1  6/304 (1.97%)  4/309 (1.29%) 
Jaundice cholestatic * 1  3/304 (0.99%)  2/309 (0.65%) 
Immune system disorders     
Contrast media allergy * 1  0/304 (0.00%)  1/309 (0.32%) 
Infections and infestations     
Abdominal abscess * 1  1/304 (0.33%)  0/309 (0.00%) 
Biliary tract infection * 1  2/304 (0.66%)  0/309 (0.00%) 
Cellulitis * 1  0/304 (0.00%)  2/309 (0.65%) 
Cytomegalovirus infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Device related infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Diverticulitis * 1  1/304 (0.33%)  0/309 (0.00%) 
Ear infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Escherichia urinary tract infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Gastroenteritis * 1  1/304 (0.33%)  0/309 (0.00%) 
Infection * 1  1/304 (0.33%)  2/309 (0.65%) 
Peritoneal infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Pneumonia * 1  2/304 (0.66%)  4/309 (1.29%) 
Respiratory tract infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Sepsis * 1  1/304 (0.33%)  5/309 (1.62%) 
Septic shock * 1  1/304 (0.33%)  0/309 (0.00%) 
Urinary tract infection * 1  1/304 (0.33%)  1/309 (0.32%) 
Urinary tract infection fungal * 1  1/304 (0.33%)  0/309 (0.00%) 
Urosepsis * 1  1/304 (0.33%)  1/309 (0.32%) 
Injury, poisoning and procedural complications     
Drug dispensing error * 1  0/304 (0.00%)  1/309 (0.32%) 
Fall * 1  0/304 (0.00%)  1/309 (0.32%) 
Hand fracture * 1  0/304 (0.00%)  1/309 (0.32%) 
Wrist fracture * 1  0/304 (0.00%)  1/309 (0.32%) 
Investigations     
Alanine aminotransferase increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Aspartate aminotransferase increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Blood alkaline phosphatase increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Blood bilirubin increased * 1  0/304 (0.00%)  1/309 (0.32%) 
Blood creatinine increased * 1  0/304 (0.00%)  1/309 (0.32%) 
Haemoglobin decreased * 1  1/304 (0.33%)  3/309 (0.97%) 
Liver function test abnormal * 1  1/304 (0.33%)  1/309 (0.32%) 
Neutrophil count decreased * 1  1/304 (0.33%)  1/309 (0.32%) 
Platelet count decreased * 1  2/304 (0.66%)  1/309 (0.32%) 
White blood cell count decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  7/304 (2.30%)  4/309 (1.29%) 
Dehydration * 1  4/304 (1.32%)  4/309 (1.29%) 
Diabetes mellitus * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypercalcaemia * 1  1/304 (0.33%)  0/309 (0.00%) 
Hyperglycaemia * 1  1/304 (0.33%)  1/309 (0.32%) 
Hypoalbuminaemia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypoglycaemia * 1  2/304 (0.66%)  0/309 (0.00%) 
Hypokalaemia * 1  4/304 (1.32%)  1/309 (0.32%) 
Hyponatraemia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypophagia * 1  1/304 (0.33%)  0/309 (0.00%) 
Malnutrition * 1  2/304 (0.66%)  0/309 (0.00%) 
Tumour lysis syndrome * 1  0/304 (0.00%)  1/309 (0.32%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/304 (0.33%)  0/309 (0.00%) 
Back pain * 1  2/304 (0.66%)  2/309 (0.65%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Duodenal neoplasm * 1  0/304 (0.00%)  1/309 (0.32%) 
Metastatic neoplasm * 1  1/304 (0.33%)  0/309 (0.00%) 
Neoplasm progression * 1  1/304 (0.33%)  0/309 (0.00%) 
Pancreatic carcinoma * 1  1/304 (0.33%)  1/309 (0.32%) 
Tumour associated fever * 1  0/304 (0.00%)  1/309 (0.32%) 
Tumour pain * 1  1/304 (0.33%)  1/309 (0.32%) 
Nervous system disorders     
Cerebral ischaemia * 1  1/304 (0.33%)  0/309 (0.00%) 
Cerebrovascular accident * 1  1/304 (0.33%)  1/309 (0.32%) 
Cognitive disorder * 1  1/304 (0.33%)  0/309 (0.00%) 
Diabetic coma * 1  0/304 (0.00%)  1/309 (0.32%) 
Dysgeusia * 1  1/304 (0.33%)  0/309 (0.00%) 
Grand mal convulsion * 1  1/304 (0.33%)  0/309 (0.00%) 
Psychomotor skills impaired * 1  1/304 (0.33%)  0/309 (0.00%) 
Reversible posterior leukoencephalopathy syndrome * 1  1/304 (0.33%)  0/309 (0.00%) 
Sensory disturbance * 1  2/304 (0.66%)  0/309 (0.00%) 
Somnolence * 1  1/304 (0.33%)  0/309 (0.00%) 
Syncope * 1  0/304 (0.00%)  1/309 (0.32%) 
Thrombotic stroke * 1  0/304 (0.00%)  1/309 (0.32%) 
Transient ischaemic attack * 1  1/304 (0.33%)  1/309 (0.32%) 
Psychiatric disorders     
Agitation * 1  0/304 (0.00%)  1/309 (0.32%) 
Anxiety * 1  1/304 (0.33%)  0/309 (0.00%) 
Confusional state * 1  4/304 (1.32%)  3/309 (0.97%) 
Depression * 1  1/304 (0.33%)  0/309 (0.00%) 
Mental status changes * 1  1/304 (0.33%)  1/309 (0.32%) 
Renal and urinary disorders     
Chromaturia * 1  0/304 (0.00%)  1/309 (0.32%) 
Renal failure * 1  3/304 (0.99%)  1/309 (0.32%) 
Renal failure acute * 1  3/304 (0.99%)  3/309 (0.97%) 
Ureteric perforation * 1  1/304 (0.33%)  0/309 (0.00%) 
Urethral obstruction * 1  0/304 (0.00%)  1/309 (0.32%) 
Urinary incontinence * 1  1/304 (0.33%)  0/309 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  2/304 (0.66%)  3/309 (0.97%) 
Hiccups * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypoxia * 1  1/304 (0.33%)  1/309 (0.32%) 
Interstitial lung disease * 1  0/304 (0.00%)  2/309 (0.65%) 
Pleural effusion * 1  0/304 (0.00%)  2/309 (0.65%) 
Pneumonitis * 1  1/304 (0.33%)  2/309 (0.65%) 
Pulmonary embolism * 1  2/304 (0.66%)  6/309 (1.94%) 
Respiratory failure * 1  1/304 (0.33%)  0/309 (0.00%) 
Skin and subcutaneous tissue disorders     
Erythema * 1  0/304 (0.00%)  1/309 (0.32%) 
Rash * 1  0/304 (0.00%)  2/309 (0.65%) 
Skin ulcer * 1  1/304 (0.33%)  0/309 (0.00%) 
Vascular disorders     
Bleeding varicose vein * 1  0/304 (0.00%)  1/309 (0.32%) 
Deep vein thrombosis * 1  1/304 (0.33%)  3/309 (0.97%) 
Hypertension * 1  1/304 (0.33%)  1/309 (0.32%) 
Hypotension * 1  1/304 (0.33%)  2/309 (0.65%) 
Phlebitis * 1  0/304 (0.00%)  1/309 (0.32%) 
Shock * 1  0/304 (0.00%)  1/309 (0.32%) 
Venous thrombosis * 1  0/304 (0.00%)  1/309 (0.32%) 
Venous thrombosis limb * 1  0/304 (0.00%)  1/309 (0.32%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Axitinib + Gemcitabine Placebo + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   276/304 (90.79%)   276/309 (89.32%) 
Blood and lymphatic system disorders     
Anaemia * 1  25/304 (8.22%)  51/309 (16.50%) 
Disseminated intravascular coagulation * 1  1/304 (0.33%)  0/309 (0.00%) 
Eosinopenia * 1  1/304 (0.33%)  0/309 (0.00%) 
Erythroblastosis * 1  0/304 (0.00%)  1/309 (0.32%) 
Erythropenia * 1  0/304 (0.00%)  1/309 (0.32%) 
Granulocytopenia * 1  0/304 (0.00%)  1/309 (0.32%) 
Haemoglobinaemia * 1  1/304 (0.33%)  2/309 (0.65%) 
Iron deficiency anaemia * 1  0/304 (0.00%)  1/309 (0.32%) 
Leukocytosis * 1  2/304 (0.66%)  1/309 (0.32%) 
Leukopenia * 1  23/304 (7.57%)  13/309 (4.21%) 
Lymphadenopathy * 1  1/304 (0.33%)  0/309 (0.00%) 
Lymphocytosis * 1  1/304 (0.33%)  0/309 (0.00%) 
Lymphopenia * 1  1/304 (0.33%)  7/309 (2.27%) 
Neutropenia * 1  73/304 (24.01%)  53/309 (17.15%) 
Neutrophilia * 1  1/304 (0.33%)  0/309 (0.00%) 
Thrombocytopenia * 1  48/304 (15.79%)  34/309 (11.00%) 
Thrombocytosis * 1  4/304 (1.32%)  3/309 (0.97%) 
Cardiac disorders     
Atrial fibrillation * 1  0/304 (0.00%)  1/309 (0.32%) 
Atrial flutter * 1  0/304 (0.00%)  1/309 (0.32%) 
Bradycardia * 1  0/304 (0.00%)  2/309 (0.65%) 
Bundle branch block right * 1  1/304 (0.33%)  0/309 (0.00%) 
Cardiovascular disorder * 1  1/304 (0.33%)  0/309 (0.00%) 
Cyanosis * 1  0/304 (0.00%)  1/309 (0.32%) 
Diastolic dysfunction * 1  1/304 (0.33%)  0/309 (0.00%) 
Mitral valve incompetence * 1  0/304 (0.00%)  1/309 (0.32%) 
Nodal rhythm * 1  1/304 (0.33%)  0/309 (0.00%) 
Palpitations * 1  4/304 (1.32%)  2/309 (0.65%) 
Pericardial effusion * 1  0/304 (0.00%)  1/309 (0.32%) 
Splinter haemorrhages * 1  1/304 (0.33%)  0/309 (0.00%) 
Supraventricular extrasystoles * 1  1/304 (0.33%)  0/309 (0.00%) 
Tachycardia * 1  1/304 (0.33%)  5/309 (1.62%) 
Ventricular tachycardia * 1  1/304 (0.33%)  0/309 (0.00%) 
Congenital, familial and genetic disorders     
Congenital foot malformation * 1  1/304 (0.33%)  0/309 (0.00%) 
Ear and labyrinth disorders     
Auricular perichondritis * 1  1/304 (0.33%)  0/309 (0.00%) 
Cerumen impaction * 1  1/304 (0.33%)  0/309 (0.00%) 
Deafness * 1  0/304 (0.00%)  1/309 (0.32%) 
Ear discomfort * 1  5/304 (1.64%)  1/309 (0.32%) 
Ear pain * 1  1/304 (0.33%)  1/309 (0.32%) 
Hypoacusis * 1  0/304 (0.00%)  1/309 (0.32%) 
Tinnitus * 1  5/304 (1.64%)  0/309 (0.00%) 
Vertigo * 1  4/304 (1.32%)  5/309 (1.62%) 
Endocrine disorders     
Hyperthyroidism * 1  2/304 (0.66%)  1/309 (0.32%) 
Hypoparathyroidism * 1  1/304 (0.33%)  0/309 (0.00%) 
Hypothyroidism * 1  15/304 (4.93%)  4/309 (1.29%) 
Thyroiditis * 1  1/304 (0.33%)  0/309 (0.00%) 
Eye disorders     
Asthenopia * 1  0/304 (0.00%)  1/309 (0.32%) 
Conjunctivitis * 1  0/304 (0.00%)  1/309 (0.32%) 
Diplopia * 1  3/304 (0.99%)  0/309 (0.00%) 
Dry eye * 1  1/304 (0.33%)  1/309 (0.32%) 
Eye pruritus * 1  0/304 (0.00%)  1/309 (0.32%) 
Eyelid oedema * 1  1/304 (0.33%)  0/309 (0.00%) 
Lacrimation increased * 1  2/304 (0.66%)  2/309 (0.65%) 
Ocular discomfort * 1  0/304 (0.00%)  1/309 (0.32%) 
Ocular hyperaemia * 1  0/304 (0.00%)  2/309 (0.65%) 
Scotoma * 1  0/304 (0.00%)  1/309 (0.32%) 
Vision blurred * 1  1/304 (0.33%)  0/309 (0.00%) 
Visual acuity reduced * 1  1/304 (0.33%)  0/309 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  3/304 (0.99%)  5/309 (1.62%) 
Abdominal distension * 1  12/304 (3.95%)  12/309 (3.88%) 
Abdominal hernia * 1  1/304 (0.33%)  0/309 (0.00%) 
Abdominal mass * 1  1/304 (0.33%)  0/309 (0.00%) 
Abdominal pain * 1  54/304 (17.76%)  52/309 (16.83%) 
Abdominal pain lower * 1  2/304 (0.66%)  5/309 (1.62%) 
Abdominal pain upper * 1  24/304 (7.89%)  24/309 (7.77%) 
Abdominal tenderness * 1  1/304 (0.33%)  0/309 (0.00%) 
Anal haemorrhage * 1  0/304 (0.00%)  1/309 (0.32%) 
Aphthous stomatitis * 1  2/304 (0.66%)  1/309 (0.32%) 
Ascites * 1  5/304 (1.64%)  9/309 (2.91%) 
Cheilitis * 1  4/304 (1.32%)  1/309 (0.32%) 
Colitis * 1  1/304 (0.33%)  0/309 (0.00%) 
Constipation * 1  88/304 (28.95%)  91/309 (29.45%) 
Dental caries * 1  0/304 (0.00%)  1/309 (0.32%) 
Diarrhoea * 1  96/304 (31.58%)  64/309 (20.71%) 
Dry mouth * 1  14/304 (4.61%)  14/309 (4.53%) 
Duodenal obstruction * 1  0/304 (0.00%)  1/309 (0.32%) 
Duodenal ulcer * 1  0/304 (0.00%)  2/309 (0.65%) 
Duodenogastric reflux * 1  0/304 (0.00%)  1/309 (0.32%) 
Dyspepsia * 1  14/304 (4.61%)  22/309 (7.12%) 
Dysphagia * 1  7/304 (2.30%)  1/309 (0.32%) 
Enteritis * 1  1/304 (0.33%)  0/309 (0.00%) 
Eructation * 1  2/304 (0.66%)  1/309 (0.32%) 
Faeces discoloured * 1  1/304 (0.33%)  0/309 (0.00%) 
Faeces pale * 1  1/304 (0.33%)  0/309 (0.00%) 
Flatulence * 1  8/304 (2.63%)  9/309 (2.91%) 
Frequent bowel movements * 1  0/304 (0.00%)  1/309 (0.32%) 
Gastritis * 1  2/304 (0.66%)  1/309 (0.32%) 
Gastritis erosive * 1  0/304 (0.00%)  1/309 (0.32%) 
Gastrointestinal disorder * 1  1/304 (0.33%)  0/309 (0.00%) 
Gastrointestinal obstruction * 1  0/304 (0.00%)  1/309 (0.32%) 
Gastrooesophageal reflux disease * 1  6/304 (1.97%)  4/309 (1.29%) 
Gingival bleeding * 1  0/304 (0.00%)  1/309 (0.32%) 
Gingival pain * 1  0/304 (0.00%)  1/309 (0.32%) 
Gingival ulceration * 1  1/304 (0.33%)  0/309 (0.00%) 
Gingivitis * 1  6/304 (1.97%)  1/309 (0.32%) 
Glossitis * 1  7/304 (2.30%)  0/309 (0.00%) 
Glossodynia * 1  2/304 (0.66%)  0/309 (0.00%) 
Haematemesis * 1  1/304 (0.33%)  2/309 (0.65%) 
Haematochezia * 1  2/304 (0.66%)  0/309 (0.00%) 
Haemorrhoids * 1  4/304 (1.32%)  5/309 (1.62%) 
Hiatus hernia * 1  1/304 (0.33%)  0/309 (0.00%) 
Ileus * 1  2/304 (0.66%)  0/309 (0.00%) 
Intestinal obstruction * 1  0/304 (0.00%)  2/309 (0.65%) 
Lip dry * 1  0/304 (0.00%)  1/309 (0.32%) 
Mouth ulceration * 1  2/304 (0.66%)  0/309 (0.00%) 
Nausea * 1  138/304 (45.39%)  112/309 (36.25%) 
Odynophagia * 1  2/304 (0.66%)  1/309 (0.32%) 
Oesophageal pain * 1  0/304 (0.00%)  1/309 (0.32%) 
Oesophagitis * 1  0/304 (0.00%)  1/309 (0.32%) 
Oral discomfort * 1  1/304 (0.33%)  0/309 (0.00%) 
Oral disorder * 1  0/304 (0.00%)  1/309 (0.32%) 
Oral dysaesthesia * 1  2/304 (0.66%)  1/309 (0.32%) 
Oral pain * 1  4/304 (1.32%)  0/309 (0.00%) 
Pancreatic insufficiency * 1  0/304 (0.00%)  1/309 (0.32%) 
Pancreatitis acute * 1  0/304 (0.00%)  1/309 (0.32%) 
Periodontitis * 1  1/304 (0.33%)  0/309 (0.00%) 
Pneumoperitoneum * 1  1/304 (0.33%)  0/309 (0.00%) 
Proctalgia * 1  0/304 (0.00%)  2/309 (0.65%) 
Rectal haemorrhage * 1  2/304 (0.66%)  1/309 (0.32%) 
Reflux gastritis * 1  1/304 (0.33%)  1/309 (0.32%) 
Reflux oesophagitis * 1  1/304 (0.33%)  1/309 (0.32%) 
Regurgitation * 1  1/304 (0.33%)  0/309 (0.00%) 
Retching * 1  3/304 (0.99%)  0/309 (0.00%) 
Salivary hypersecretion * 1  1/304 (0.33%)  1/309 (0.32%) 
Steatorrhoea * 1  2/304 (0.66%)  2/309 (0.65%) 
Stomatitis * 1  52/304 (17.11%)  12/309 (3.88%) 
Thrombosis mesenteric vessel * 1  0/304 (0.00%)  1/309 (0.32%) 
Toothache * 1  3/304 (0.99%)  2/309 (0.65%) 
Vomiting * 1  91/304 (29.93%)  95/309 (30.74%) 
Mass * 1  1/304 (0.33%)  0/309 (0.00%) 
General disorders     
Adhesion * 1  0/304 (0.00%)  1/309 (0.32%) 
Asthenia * 1  38/304 (12.50%)  38/309 (12.30%) 
Catheter site erythema * 1  0/304 (0.00%)  2/309 (0.65%) 
Catheter site haemorrhage * 1  0/304 (0.00%)  1/309 (0.32%) 
Catheter site pain * 1  0/304 (0.00%)  2/309 (0.65%) 
Catheter site pruritus * 1  0/304 (0.00%)  1/309 (0.32%) 
Chest discomfort * 1  2/304 (0.66%)  2/309 (0.65%) 
Chest pain * 1  10/304 (3.29%)  6/309 (1.94%) 
Chills * 1  13/304 (4.28%)  11/309 (3.56%) 
Device occlusion * 1  0/304 (0.00%)  1/309 (0.32%) 
Early satiety * 1  1/304 (0.33%)  1/309 (0.32%) 
Face oedema * 1  1/304 (0.33%)  0/309 (0.00%) 
Fatigue * 1  125/304 (41.12%)  113/309 (36.57%) 
Feeling cold * 1  1/304 (0.33%)  1/309 (0.32%) 
Feeling hot * 1  0/304 (0.00%)  1/309 (0.32%) 
General physical health deterioration * 1  6/304 (1.97%)  2/309 (0.65%) 
Generalised oedema * 1  0/304 (0.00%)  1/309 (0.32%) 
Hernia pain * 1  0/304 (0.00%)  1/309 (0.32%) 
Hyperthermia * 1  1/304 (0.33%)  1/309 (0.32%) 
Influenza like illness * 1  9/304 (2.96%)  9/309 (2.91%) 
Injection site extravasation * 1  1/304 (0.33%)  0/309 (0.00%) 
Injection site reaction * 1  1/304 (0.33%)  2/309 (0.65%) 
Malaise * 1  0/304 (0.00%)  2/309 (0.65%) 
Mucosal dryness * 1  2/304 (0.66%)  0/309 (0.00%) 
Mucosal inflammation * 1  34/304 (11.18%)  13/309 (4.21%) 
Oedema * 1  6/304 (1.97%)  5/309 (1.62%) 
Oedema peripheral * 1  22/304 (7.24%)  46/309 (14.89%) 
Pain * 1  16/304 (5.26%)  7/309 (2.27%) 
Performance status decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Pyrexia * 1  38/304 (12.50%)  44/309 (14.24%) 
Thirst * 1  2/304 (0.66%)  1/309 (0.32%) 
Thrombosis in device * 1  2/304 (0.66%)  0/309 (0.00%) 
Ulcer * 1  0/304 (0.00%)  1/309 (0.32%) 
Hepatobiliary disorders     
Bile duct obstruction * 1  2/304 (0.66%)  1/309 (0.32%) 
Cholangitis * 1  4/304 (1.32%)  4/309 (1.29%) 
Cholestasis * 1  0/304 (0.00%)  1/309 (0.32%) 
Cytolytic hepatitis * 1  0/304 (0.00%)  1/309 (0.32%) 
Hepatic function abnormal * 1  4/304 (1.32%)  2/309 (0.65%) 
Hepatic pain * 1  1/304 (0.33%)  0/309 (0.00%) 
Hepatomegaly * 1  0/304 (0.00%)  2/309 (0.65%) 
Hepatorenal syndrome * 1  0/304 (0.00%)  1/309 (0.32%) 
Hepatotoxicity * 1  6/304 (1.97%)  1/309 (0.32%) 
Hyperbilirubinaemia * 1  6/304 (1.97%)  9/309 (2.91%) 
Jaundice * 1  3/304 (0.99%)  1/309 (0.32%) 
Liver disorder * 1  0/304 (0.00%)  1/309 (0.32%) 
Liver tenderness * 1  1/304 (0.33%)  0/309 (0.00%) 
Portal vein thrombosis * 1  0/304 (0.00%)  2/309 (0.65%) 
Immune system disorders     
Contrast media allergy * 1  0/304 (0.00%)  1/309 (0.32%) 
Food allergy * 1  1/304 (0.33%)  0/309 (0.00%) 
Hypersensitivity * 1  2/304 (0.66%)  1/309 (0.32%) 
Seasonal allergy * 1  0/304 (0.00%)  1/309 (0.32%) 
Infections and infestations     
Abscess * 1  1/304 (0.33%)  0/309 (0.00%) 
Acariasis * 1  0/304 (0.00%)  1/309 (0.32%) 
Arthritis infective * 1  1/304 (0.33%)  0/309 (0.00%) 
Bacterial infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Biliary tract infection * 1  2/304 (0.66%)  1/309 (0.32%) 
Bronchitis * 1  3/304 (0.99%)  1/309 (0.32%) 
Candidiasis * 1  2/304 (0.66%)  0/309 (0.00%) 
Catheter site infection * 1  1/304 (0.33%)  2/309 (0.65%) 
Cellulitis * 1  3/304 (0.99%)  4/309 (1.29%) 
Cystitis * 1  4/304 (1.32%)  3/309 (0.97%) 
Device related infection * 1  1/304 (0.33%)  1/309 (0.32%) 
Enteritis infectious * 1  0/304 (0.00%)  1/309 (0.32%) 
Erysipelas * 1  0/304 (0.00%)  2/309 (0.65%) 
Escherichia infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Eye infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Fungal infection * 1  1/304 (0.33%)  1/309 (0.32%) 
Furuncle * 1  1/304 (0.33%)  1/309 (0.32%) 
Gastroenteritis * 1  1/304 (0.33%)  2/309 (0.65%) 
Infection * 1  4/304 (1.32%)  1/309 (0.32%) 
Influenza * 1  1/304 (0.33%)  2/309 (0.65%) 
Localised infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Lower respiratory tract infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Lung infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Lymphangitis * 1  0/304 (0.00%)  1/309 (0.32%) 
Nasopharyngitis * 1  9/304 (2.96%)  7/309 (2.27%) 
Oesophageal candidiasis * 1  1/304 (0.33%)  0/309 (0.00%) 
Oral candidiasis * 1  6/304 (1.97%)  5/309 (1.62%) 
Oral fungal infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Oral herpes * 1  3/304 (0.99%)  1/309 (0.32%) 
Oral infection * 1  0/304 (0.00%)  1/309 (0.32%) 
Oropharyngeal candidiasis * 1  0/304 (0.00%)  1/309 (0.32%) 
Perichondritis * 1  0/304 (0.00%)  1/309 (0.32%) 
Pharyngitis * 1  6/304 (1.97%)  0/309 (0.00%) 
Pharyngotonsillitis * 1  0/304 (0.00%)  1/309 (0.32%) 
Pneumonia * 1  1/304 (0.33%)  1/309 (0.32%) 
Pseudomonas infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Respiratory tract infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Rhinitis * 1  1/304 (0.33%)  3/309 (0.97%) 
Sepsis * 1  0/304 (0.00%)  2/309 (0.65%) 
Septic encephalopathy * 1  1/304 (0.33%)  0/309 (0.00%) 
Septic shock * 1  0/304 (0.00%)  1/309 (0.32%) 
Sinusitis * 1  3/304 (0.99%)  0/309 (0.00%) 
Skin candida * 1  1/304 (0.33%)  0/309 (0.00%) 
Tooth abscess * 1  3/304 (0.99%)  0/309 (0.00%) 
Tooth infection * 1  1/304 (0.33%)  1/309 (0.32%) 
Upper respiratory tract infection * 1  8/304 (2.63%)  2/309 (0.65%) 
Urinary tract infection * 1  9/304 (2.96%)  11/309 (3.56%) 
Viral infection * 1  1/304 (0.33%)  0/309 (0.00%) 
Injury, poisoning and procedural complications     
Anal injury * 1  2/304 (0.66%)  0/309 (0.00%) 
Arthropod bite * 1  1/304 (0.33%)  0/309 (0.00%) 
Burn oesophageal * 1  1/304 (0.33%)  0/309 (0.00%) 
Contusion * 1  1/304 (0.33%)  2/309 (0.65%) 
Drug toxicity * 1  0/304 (0.00%)  1/309 (0.32%) 
Eschar * 1  0/304 (0.00%)  1/309 (0.32%) 
Fall * 1  2/304 (0.66%)  2/309 (0.65%) 
Feeding tube complication * 1  0/304 (0.00%)  1/309 (0.32%) 
Humerus fracture * 1  1/304 (0.33%)  0/309 (0.00%) 
Incision site pain * 1  1/304 (0.33%)  0/309 (0.00%) 
Incisional hernia * 1  0/304 (0.00%)  1/309 (0.32%) 
Medication error * 1  1/304 (0.33%)  1/309 (0.32%) 
Overdose * 1  1/304 (0.33%)  0/309 (0.00%) 
Post procedural complication * 1  0/304 (0.00%)  1/309 (0.32%) 
Post procedural haematoma * 1  0/304 (0.00%)  1/309 (0.32%) 
Post procedural haemorrhage * 1  1/304 (0.33%)  0/309 (0.00%) 
Postoperative wound complication * 1  1/304 (0.33%)  0/309 (0.00%) 
Procedural pain * 1  0/304 (0.00%)  1/309 (0.32%) 
Skin laceration * 1  0/304 (0.00%)  1/309 (0.32%) 
Spinal compression fracture * 1  0/304 (0.00%)  1/309 (0.32%) 
Wound * 1  0/304 (0.00%)  2/309 (0.65%) 
Wound dehiscence * 1  1/304 (0.33%)  0/309 (0.00%) 
Investigations     
Activated partial thromboplastin time prolonged * 1  2/304 (0.66%)  1/309 (0.32%) 
Alanine aminotransferase * 1  1/304 (0.33%)  2/309 (0.65%) 
Alanine aminotransferase increased * 1  29/304 (9.54%)  24/309 (7.77%) 
Ammonia increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Aspartate aminotransferase * 1  1/304 (0.33%)  2/309 (0.65%) 
Aspartate aminotransferase increased * 1  24/304 (7.89%)  21/309 (6.80%) 
Bacterial test positive * 1  0/304 (0.00%)  1/309 (0.32%) 
Blood albumin decreased * 1  2/304 (0.66%)  1/309 (0.32%) 
Blood alkaline phosphatase * 1  1/304 (0.33%)  1/309 (0.32%) 
Blood alkaline phosphatase increased * 1  15/304 (4.93%)  11/309 (3.56%) 
Blood amylase increased * 1  2/304 (0.66%)  0/309 (0.00%) 
Blood bilirubin * 1  1/304 (0.33%)  1/309 (0.32%) 
Blood bilirubin increased * 1  6/304 (1.97%)  9/309 (2.91%) 
Blood creatinine increased * 1  1/304 (0.33%)  5/309 (1.62%) 
Blood culture positive * 1  1/304 (0.33%)  0/309 (0.00%) 
Blood fibrinogen increased * 1  1/304 (0.33%)  1/309 (0.32%) 
Blood glucose decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Blood glucose increased * 1  3/304 (0.99%)  6/309 (1.94%) 
Blood lactate dehydrogenase increased * 1  2/304 (0.66%)  1/309 (0.32%) 
Blood magnesium decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Blood potassium decreased * 1  0/304 (0.00%)  3/309 (0.97%) 
Blood potassium increased * 1  0/304 (0.00%)  1/309 (0.32%) 
Blood pressure increased * 1  3/304 (0.99%)  0/309 (0.00%) 
Blood sodium decreased * 1  0/304 (0.00%)  1/309 (0.32%) 
Blood thyroid stimulating hormone decreased * 1  2/304 (0.66%)  1/309 (0.32%) 
Blood thyroid stimulating hormone increased * 1  16/304 (5.26%)  0/309 (0.00%) 
Blood urea increased * 1  2/304 (0.66%)  0/309 (0.00%) 
Blood urine * 1  0/304 (0.00%)  1/309 (0.32%) 
Blood urine present * 1  0/304 (0.00%)  1/309 (0.32%) 
Body temperature increased * 1  0/304 (0.00%)  1/309 (0.32%) 
C-reactive protein increased * 1  3/304 (0.99%)  3/309 (0.97%) 
Eastern cooperative oncology group performance status worsened * 1  0/304 (0.00%)  1/309 (0.32%) 
Electrocardiogram QRS complex abnormal * 1  1/304 (0.33%)  0/309 (0.00%) 
Electrocardiogram QT prolonged * 1  1/304 (0.33%)  0/309 (0.00%) 
Fibrin D dimer increased * 1  1/304 (0.33%)  1/309 (0.32%) 
Gamma-glutamyltransferase increased * 1  0/304 (0.00%)  2/309 (0.65%) 
Haematocrit decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Haemoglobin * 1  0/304 (0.00%)  3/309 (0.97%) 
Haemoglobin decreased * 1  18/304 (5.92%)  26/309 (8.41%) 
International normalised ratio increased * 1  1/304 (0.33%)  2/309 (0.65%) 
Liver function test abnormal * 1  4/304 (1.32%)  1/309 (0.32%) 
Lymph node palpable * 1  1/304 (0.33%)  0/309 (0.00%) 
Lymphocyte count decreased * 1  6/304 (1.97%)  4/309 (1.29%) 
Mean cell volume abnormal * 1  1/304 (0.33%)  0/309 (0.00%) 
Monocyte count decreased * 1  2/304 (0.66%)  0/309 (0.00%) 
Monocyte count increased * 1  0/304 (0.00%)  1/309 (0.32%) 
Monocyte percentage increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Neutrophil count * 1  5/304 (1.64%)  0/309 (0.00%) 
Neutrophil count decreased * 1  31/304 (10.20%)  38/309 (12.30%) 
Neutrophil percentage decreased * 1  0/304 (0.00%)  1/309 (0.32%) 
Oxygen saturation decreased * 1  0/304 (0.00%)  1/309 (0.32%) 
Platelet count * 1  4/304 (1.32%)  1/309 (0.32%) 
Platelet count decreased * 1  43/304 (14.14%)  40/309 (12.94%) 
Platelet count increased * 1  0/304 (0.00%)  1/309 (0.32%) 
Protein total decreased * 1  1/304 (0.33%)  1/309 (0.32%) 
Protein urine * 1  1/304 (0.33%)  2/309 (0.65%) 
Protein urine present * 1  1/304 (0.33%)  0/309 (0.00%) 
Prothrombin time abnormal * 1  0/304 (0.00%)  1/309 (0.32%) 
Prothrombin time prolonged * 1  0/304 (0.00%)  2/309 (0.65%) 
Prothrombin time shortened * 1  0/304 (0.00%)  1/309 (0.32%) 
Red blood cell count decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Red cell distribution width increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Thyroxine free increased * 1  1/304 (0.33%)  1/309 (0.32%) 
Transaminases increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Tri-iodothyronine free decreased * 1  0/304 (0.00%)  1/309 (0.32%) 
Tri-iodothyronine free increased * 1  1/304 (0.33%)  0/309 (0.00%) 
Urine output decreased * 1  1/304 (0.33%)  0/309 (0.00%) 
Weight decreased * 1  44/304 (14.47%)  29/309 (9.39%) 
Weight increased * 1  0/304 (0.00%)  2/309 (0.65%) 
White blood cell count * 1  2/304 (0.66%)  1/309 (0.32%) 
White blood cell count decreased * 1  20/304 (6.58%)  16/309 (5.18%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  115/304 (37.83%)  87/309 (28.16%) 
Dehydration * 1  5/304 (1.64%)  12/309 (3.88%) 
Diabetes mellitus * 1  1/304 (0.33%)  1/309 (0.32%) 
Fluid overload * 1  0/304 (0.00%)  2/309 (0.65%) 
Gout * 1  3/304 (0.99%)  1/309 (0.32%) 
Hyperammonaemia * 1  1/304 (0.33%)  0/309 (0.00%) 
Hypercalcaemia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hyperglycaemia * 1  9/304 (2.96%)  5/309 (1.62%) 
Hyperkalaemia * 1  0/304 (0.00%)  3/309 (0.97%) 
Hyperlipasaemia * 1  1/304 (0.33%)  0/309 (0.00%) 
Hypernatraemia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hyperuricaemia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypoalbuminaemia * 1  4/304 (1.32%)  5/309 (1.62%) 
Hypocalcaemia * 1  1/304 (0.33%)  4/309 (1.29%) 
Hypoglycaemia * 1  2/304 (0.66%)  3/309 (0.97%) 
Hypokalaemia * 1  13/304 (4.28%)  8/309 (2.59%) 
Hypomagnesaemia * 1  0/304 (0.00%)  2/309 (0.65%) 
Hyponatraemia * 1  4/304 (1.32%)  6/309 (1.94%) 
Hypophosphataemia * 1  0/304 (0.00%)  2/309 (0.65%) 
Hypoproteinaemia * 1  1/304 (0.33%)  0/309 (0.00%) 
Lactic acidosis * 1  1/304 (0.33%)  0/309 (0.00%) 
Malnutrition * 1  2/304 (0.66%)  2/309 (0.65%) 
Metabolic acidosis * 1  0/304 (0.00%)  1/309 (0.32%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  10/304 (3.29%)  11/309 (3.56%) 
Back pain * 1  34/304 (11.18%)  30/309 (9.71%) 
Bone pain * 1  3/304 (0.99%)  2/309 (0.65%) 
Bone swelling * 1  0/304 (0.00%)  1/309 (0.32%) 
Flank pain * 1  2/304 (0.66%)  5/309 (1.62%) 
Gouty arthritis * 1  0/304 (0.00%)  1/309 (0.32%) 
Intervertebral disc degeneration * 1  0/304 (0.00%)  1/309 (0.32%) 
Joint swelling * 1  0/304 (0.00%)  4/309 (1.29%) 
Muscle contracture * 1  1/304 (0.33%)  2/309 (0.65%) 
Muscle spasms * 1  7/304 (2.30%)  3/309 (0.97%) 
Muscle twitching * 1  1/304 (0.33%)  0/309 (0.00%) 
Muscular weakness * 1  4/304 (1.32%)  3/309 (0.97%) 
Musculoskeletal chest pain * 1  2/304 (0.66%)  7/309 (2.27%) 
Musculoskeletal discomfort * 1  1/304 (0.33%)  1/309 (0.32%) 
Musculoskeletal pain * 1  13/304 (4.28%)  7/309 (2.27%) 
Musculoskeletal stiffness * 1  1/304 (0.33%)  1/309 (0.32%) 
Myalgia * 1  11/304 (3.62%)  14/309 (4.53%) 
Neck pain * 1  1/304 (0.33%)  1/309 (0.32%) 
Osteoarthritis * 1  1/304 (0.33%)  0/309 (0.00%) 
Pain in extremity * 1  8/304 (2.63%)  11/309 (3.56%) 
Pain in jaw * 1  1/304 (0.33%)  0/309 (0.00%) 
Synovial cyst * 1  0/304 (0.00%)  1/309 (0.32%) 
Torticollis * 1  0/304 (0.00%)  1/309 (0.32%) 
Trigger finger * 1  1/304 (0.33%)  0/309 (0.00%) 
Upper extremity mass * 1  0/304 (0.00%)  1/309 (0.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain * 1  8/304 (2.63%)  4/309 (1.29%) 
Tumour associated fever * 1  0/304 (0.00%)  1/309 (0.32%) 
Tumour pain * 1  2/304 (0.66%)  2/309 (0.65%) 
Nervous system disorders     
Ageusia * 1  0/304 (0.00%)  2/309 (0.65%) 
Amnesia * 1  3/304 (0.99%)  2/309 (0.65%) 
Anaesthesia * 1  1/304 (0.33%)  0/309 (0.00%) 
Aphasia * 1  1/304 (0.33%)  0/309 (0.00%) 
Aphonia * 1  1/304 (0.33%)  0/309 (0.00%) 
Cognitive disorder * 1  1/304 (0.33%)  0/309 (0.00%) 
Cranial nerve disorder * 1  1/304 (0.33%)  0/309 (0.00%) 
Dizziness * 1  10/304 (3.29%)  17/309 (5.50%) 
Dysaesthesia * 1  0/304 (0.00%)  1/309 (0.32%) 
Dysarthria * 1  0/304 (0.00%)  1/309 (0.32%) 
Dysgeusia * 1  25/304 (8.22%)  14/309 (4.53%) 
Extrapyramidal disorder * 1  0/304 (0.00%)  1/309 (0.32%) 
Headache * 1  45/304 (14.80%)  26/309 (8.41%) 
Hyperaesthesia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypersomnia * 1  0/304 (0.00%)  1/309 (0.32%) 
Hypoaesthesia * 1  6/304 (1.97%)  2/309 (0.65%) 
Lethargy * 1  8/304 (2.63%)  12/309 (3.88%) 
Loss of consciousness * 1  0/304 (0.00%)  1/309 (0.32%) 
Memory impairment * 1  1/304 (0.33%)  1/309 (0.32%) 
Metabolic encephalopathy * 1  1/304 (0.33%)  0/309 (0.00%) 
Migraine * 1  1/304 (0.33%)  0/309 (0.00%) 
Myoclonus * 1  1/304 (0.33%)  0/309 (0.00%) 
Neuropathy peripheral * 1  3/304 (0.99%)  1/309 (0.32%) 
Paraesthesia * 1  4/304 (1.32%)  4/309 (1.29%) 
Peripheral sensory neuropathy * 1  3/304 (0.99%)  7/309 (2.27%) 
Polyneuropathy * 1  1/304 (0.33%)  0/309 (0.00%) 
Poor quality sleep * 1  1/304 (0.33%)  0/309 (0.00%) 
Sciatica * 1  1/304 (0.33%)  1/309 (0.32%) 
Sinus headache * 1  0/304 (0.00%)  1/309 (0.32%) 
Somnolence * 1  2/304 (0.66%)  1/309 (0.32%) 
Syncope * 1  2/304 (0.66%)  1/309 (0.32%) 
Tremor * 1  3/304 (0.99%)  1/309 (0.32%) 
Psychiatric disorders     
Agitation * 1  0/304 (0.00%)  1/309 (0.32%) 
Anxiety * 1  16/304 (5.26%)  19/309 (6.15%) 
Aversion * 1  3/304 (0.99%)  0/309 (0.00%) 
Confusional state * 1  7/304 (2.30%)  3/309 (0.97%) 
Decreased activity * 1  0/304 (0.00%)  1/309 (0.32%) 
Delirium * 1  3/304 (0.99%)  0/309 (0.00%) 
Depression * 1  14/304 (4.61%)  10/309 (3.24%) 
Dysphoria * 1  1/304 (0.33%)  0/309 (0.00%) 
Hallucination * 1  2/304 (0.66%)  3/309 (0.97%) 
Hallucinations, mixed * 1  0/304 (0.00%)  1/309 (0.32%) 
Insomnia * 1  25/304 (8.22%)  18/309 (5.83%) 
Loss of libido * 1  1/304 (0.33%)  0/309 (0.00%) 
Nightmare * 1  1/304 (0.33%)  0/309 (0.00%) 
Paranoia * 1  1/304 (0.33%)  0/309 (0.00%) 
Sleep disorder * 1  1/304 (0.33%)  0/309 (0.00%) 
Vomiting psychogenic * 1  0/304 (0.00%)  1/309 (0.32%) 
Renal and urinary disorders     
Bladder pain * 1  1/304 (0.33%)  0/309 (0.00%) 
Chromaturia * 1  1/304 (0.33%)  0/309 (0.00%) 
Dysuria * 1  5/304 (1.64%)  1/309 (0.32%) 
Haematuria * 1  4/304 (1.32%)  4/309 (1.29%) 
Hydronephrosis * 1  1/304 (0.33%)  0/309 (0.00%) 
Micturition urgency * 1  0/304 (0.00%)  1/309 (0.32%) 
Pollakiuria * 1  4/304 (1.32%)  3/309 (0.97%) 
Polyuria * 1  0/304 (0.00%)  1/309 (0.32%) 
Proteinuria * 1  17/304 (5.59%)  12/309 (3.88%) 
Pyuria * 1  0/304 (0.00%)  1/309 (0.32%) 
Renal failure acute * 1  0/304 (0.00%)  1/309 (0.32%) 
Renal impairment * 1  1/304 (0.33%)  0/309 (0.00%) 
Urethral pain * 1  0/304 (0.00%)  1/309 (0.32%) 
Urinary incontinence * 1  0/304 (0.00%)  2/309 (0.65%) 
Reproductive system and breast disorders     
Breast enlargement * 1  0/304 (0.00%)  1/309 (0.32%) 
Genital haemorrhage * 1  0/304 (0.00%)  1/309 (0.32%) 
Menopausal symptoms * 1  1/304 (0.33%)  0/309 (0.00%) 
Metrorrhagia * 1  1/304 (0.33%)  0/309 (0.00%) 
Prostatism * 1  0/304 (0.00%)  1/309 (0.32%) 
Pruritus genital * 1  1/304 (0.33%)  0/309 (0.00%) 
Scrotal ulcer * 1  1/304 (0.33%)  0/309 (0.00%) 
Vaginal haemorrhage * 1  0/304 (0.00%)  1/309 (0.32%) 
Vulvovaginal dryness * 1  2/304 (0.66%)  0/309 (0.00%) 
Vulvovaginal pruritus * 1  0/304 (0.00%)  1/309 (0.32%) 
Respiratory, thoracic and mediastinal disorders     
Asphyxia * 1  1/304 (0.33%)  0/309 (0.00%) 
Asthma * 1  0/304 (0.00%)  2/309 (0.65%) 
Atelectasis * 1  1/304 (0.33%)  1/309 (0.32%)