A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00615056
Collaborator
(none)
171
83
4
49
2.1
0
Study Details
Study Description
Brief Summary
The study is designed to demonstrate that the combination of AG-013736 with either FOLFIRI or FOLFOX is superior to FOLFIRI or FOLFOX in combination with bevacizumab (Avastin) in delaying tumor progression in the second-line treatment of patients with metastatic colorectal cancer after failure of an irinotecan or oxaliplatin-containing first-line regimen.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
171 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Phase 2 Study Of FOLFOX Or FOLFIRI With AG-013736 Or Bevacizumab (Avastin) In Patients With Metastatic Colorectal Cancer After Failure Of An Irinotecan Or Oxaliplatin-Containing First-Line Regimen
Study Start Date
:
Mar 1, 2008
Actual Primary Completion Date
:
Mar 1, 2011
Actual Study Completion Date
:
Apr 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: B Bevacizumab (avastin) |
Drug: Bevacizumab (avastin)
Bevacizumab intravenous [IV] infusion 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU])
Irinotecan (180 mg/m²) intravenous infusion [IV] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) intravenous [IV] and a subsequent 5-FU infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
|
| Experimental: C AG-013736 (axitinib) |
Drug: AG-013736 (axitinib)
Axitinib is given at a starting dose of 5 mg twice daily [BID] continuous dosing until disease progression, intolerance or withdrawal of consent.
Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
Oxaliplatin (85 mg/m²) intravenous infusion [IV] over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
|
| Experimental: A AG-013736 (axitinib) |
Drug: AG-013736 (axitinib)
Axitinib is given at a starting dose of 5 mg twice daily [BID] continuous dosing until disease progression, intolerance or withdrawal of consent.
Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU])
Irinotecan (180 mg/m²) intravenous infusion [IV] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) IV and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
|
| Active Comparator: D bevacizumab (avastin) |
Drug: Bevacizumab (avastin)
Bevacizumab intravenous infusion [IV] 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
Oxaliplatin (85 mg/m²) IV infusion over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks]
Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Secondary Outcome Measures
- Overall Survival (OS) [Baseline until death or up to 1 year after the randomization of last participant]
Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
- Percentage of Participants With Objective Response (OR) [Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks]
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are 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.
- Duration of Response (DR) [Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks]
Time in months 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 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
- Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal [Baseline, Day 1 of cycles 2- 5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal]
Symptom severity score is comprised of average of 14 MDASI-D core items (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling and diarrhea) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last week; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome. Total average score range: 0 to 10.
- Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal [Baseline, Day 1 of cycle 2-5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal]
Symptom Interference score is comprised of the average of 6 items on feeling or function from the MDASI-D core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last week; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome. Total average score range: 0 to 10.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically documented colorectal cancer plus one of the following:
-
Failure of one prior irinotecan- or oxaliplatin-containing regimen, or
-
Adjuvant refractory to irinotecan- or oxaliplatin-containing regimen.
Exclusion Criteria:
-
Prior treatment in first line metastatic setting with more than one regimen
-
Prior irradiation of more than 25% of bone marrow.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Mobile | Alabama | United States | 36608 |
| 2 | Pfizer Investigational Site | Antioch | California | United States | 94531 |
| 3 | Pfizer Investigational Site | Los Angeles | California | United States | 90095-6984 |
| 4 | Pfizer Investigational Site | Los Angeles | California | United States | 90095 |
| 5 | Pfizer Investigational Site | Pleasant Hill | California | United States | 94523 |
| 6 | Pfizer Investigational Site | San Leandro | California | United States | 94578 |
| 7 | Pfizer Investigational Site | Santa Monica | California | United States | 90404 |
| 8 | Pfizer Investigational Site | Aurora | Colorado | United States | 80045 |
| 9 | Pfizer Investigational Site | Bonita Springs | Florida | United States | 34135 |
| 10 | Pfizer Investigational Site | Bradenton | Florida | United States | 34209 |
| 11 | Pfizer Investigational Site | Cape Coral | Florida | United States | 33914 |
| 12 | Pfizer Investigational Site | Cape Coral | Florida | United States | 33990 |
| 13 | Pfizer Investigational Site | Englewood | Florida | United States | 34223 |
| 14 | Pfizer Investigational Site | Fort Myers | Florida | United States | 33901-8108 |
| 15 | Pfizer Investigational Site | Fort Myers | Florida | United States | 33905 |
| 16 | Pfizer Investigational Site | Fort Myers | Florida | United States | 33908 |
| 17 | Pfizer Investigational Site | Fort Myers | Florida | United States | 33916 |
| 18 | Pfizer Investigational Site | Naples | Florida | United States | 34102 |
| 19 | Pfizer Investigational Site | Naples | Florida | United States | 34119 |
| 20 | Pfizer Investigational Site | Port Charlotte | Florida | United States | 33980 |
| 21 | Pfizer Investigational Site | Sarasota | Florida | United States | 34232 |
| 22 | Pfizer Investigational Site | Sarasota | Florida | United States | 34236 |
| 23 | Pfizer Investigational Site | Venice | Florida | United States | 34285 |
| 24 | Pfizer Investigational Site | Venice | Florida | United States | 34292 |
| 25 | Pfizer Investigational Site | Atlanta | Georgia | United States | 30318 |
| 26 | Pfizer Investigational Site | Ringgold | Georgia | United States | 30736 |
| 27 | Pfizer Investigational Site | Dubuque | Iowa | United States | 52001 |
| 28 | Pfizer Investigational Site | Crestview Hills | Kentucky | United States | 41017 |
| 29 | Pfizer Investigational Site | Paducah | Kentucky | United States | 42002 |
| 30 | Pfizer Investigational Site | Paducah | Kentucky | United States | 42003 |
| 31 | Pfizer Investigational Site | Baltimore | Maryland | United States | 21237 |
| 32 | Pfizer Investigational Site | New Albany | Mississippi | United States | 38652 |
| 33 | Pfizer Investigational Site | Cincinnati | Ohio | United States | 45219 |
| 34 | Pfizer Investigational Site | Cincinnati | Ohio | United States | 45230 |
| 35 | Pfizer Investigational Site | Cincinnati | Ohio | United States | 45236 |
| 36 | Pfizer Investigational Site | Cincinnati | Ohio | United States | 45238 |
| 37 | Pfizer Investigational Site | Cincinnati | Ohio | United States | 45242 |
| 38 | Pfizer Investigational Site | Cincinnati | Ohio | United States | 45248 |
| 39 | Pfizer Investigational Site | Fairfield | Ohio | United States | 45014 |
| 40 | Pfizer Investigational Site | Hamilton | Ohio | United States | 45013 |
| 41 | Pfizer Investigational Site | Chattanooga | Tennessee | United States | 37404 |
| 42 | Pfizer Investigational Site | Franklin | Tennessee | United States | 37067 |
| 43 | Pfizer Investigational Site | Gallatin | Tennessee | United States | 37066 |
| 44 | Pfizer Investigational Site | Germantown | Tennessee | United States | 38138 |
| 45 | Pfizer Investigational Site | Hermitage | Tennessee | United States | 37076 |
| 46 | Pfizer Investigational Site | Hixson | Tennessee | United States | 37343 |
| 47 | Pfizer Investigational Site | Lebanon | Tennessee | United States | 37087 |
| 48 | Pfizer Investigational Site | Murfreesboro | Tennessee | United States | 37130 |
| 49 | Pfizer Investigational Site | Nashville | Tennessee | United States | 37203 |
| 50 | Pfizer Investigational Site | Nashville | Tennessee | United States | 37205 |
| 51 | Pfizer Investigational Site | Nashville | Tennessee | United States | 37207 |
| 52 | Pfizer Investigational Site | Nashville | Tennessee | United States | 37211 |
| 53 | Pfizer Investigational Site | Nashville | Tennessee | United States | 37232 |
| 54 | Pfizer Investigational Site | Paris | Tennessee | United States | 38242 |
| 55 | Pfizer Investigational Site | Smyrna | Tennessee | United States | 37167 |
| 56 | Pfizer Investigational Site | Union City | Tennessee | United States | 38261 |
| 57 | Pfizer Investigational Site | Corpus Christi | Texas | United States | 78463 |
| 58 | Pfizer Investigational Site | Mechanicsville | Virginia | United States | 23116 |
| 59 | Pfizer Investigational Site | Midlothian | Virginia | United States | 23114 |
| 60 | Pfizer Investigational Site | Richmond | Virginia | United States | 23230 |
| 61 | Pfizer Investigational Site | Richmond | Virginia | United States | 23235 |
| 62 | Pfizer Investigational Site | Greenfield Park | Quebec | Canada | J4V 2H1 |
| 63 | Pfizer Investigational Site | Levis | Quebec | Canada | G6V 3Z1 |
| 64 | Pfizer Investigational Site | Montreal | Quebec | Canada | H2X 3J4 |
| 65 | Pfizer Investigational Site | Lille | France | 59020 | |
| 66 | Pfizer Investigational Site | Montpellier | France | 34094 | |
| 67 | Pfizer Investigational Site | Paris | France | 75012 | |
| 68 | Pfizer Investigational Site | Villejuif | France | 94805 | |
| 69 | Pfizer Investigational Site | Genova | Italy | 16132 | |
| 70 | Pfizer Investigational Site | Padova | Italy | 35128 | |
| 71 | Pfizer Investigational Site | Roma | Italy | 00152 | |
| 72 | Pfizer Investigational Site | Roma | Italy | 00168 | |
| 73 | Pfizer Investigational Site | Kashiwa | Chiba | Japan | |
| 74 | Pfizer Investigational Site | Suntougun | Shizuoka | Japan | |
| 75 | Pfizer Investigational Site | Chuo-ku | Tokyo | Japan | |
| 76 | Pfizer Investigational Site | Daegu | Korea, Republic of | 700-721 | |
| 77 | Pfizer Investigational Site | Jeollanam-do | Korea, Republic of | 519-809 | |
| 78 | Pfizer Investigational Site | Seoul | Korea, Republic of | 139-706 | |
| 79 | Pfizer Investigational Site | Warszawa | Poland | 02-097 | |
| 80 | Pfizer Investigational Site | Warszawa | Poland | 02-781 | |
| 81 | Pfizer Investigational Site | L'hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 82 | Pfizer Investigational Site | Sabadell | Barcelona | Spain | 08208 |
| 83 | Pfizer Investigational Site | Madrid | Spain | 28033 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00615056
Other Study ID Numbers:
- A4061034
First Posted:
Feb 14, 2008
Last Update Posted:
Apr 19, 2013
Last Verified:
Apr 1, 2013
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Period Title: Overall Study | ||||
| STARTED | 49 | 51 | 36 | 35 |
| Treated | 46 | 51 | 36 | 35 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 49 | 51 | 36 | 35 |
Baseline Characteristics
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Total of all reporting groups |
| Overall Participants | 49 | 51 | 36 | 35 | 171 |
| Age, Customized (Number) [Number] | |||||
| 18 to 44 years |
5
10.2%
|
6
11.8%
|
3
8.3%
|
1
2.9%
|
15
8.8%
|
| 45 to 64 years |
30
61.2%
|
34
66.7%
|
21
58.3%
|
22
62.9%
|
107
62.6%
|
| Greater than and equal to 65 years |
14
28.6%
|
11
21.6%
|
12
33.3%
|
12
34.3%
|
49
28.7%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
18
36.7%
|
24
47.1%
|
20
55.6%
|
11
31.4%
|
73
42.7%
|
| Male |
31
63.3%
|
27
52.9%
|
16
44.4%
|
24
68.6%
|
98
57.3%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). |
| Time Frame | Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized. |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Measure Participants | 49 | 51 | 36 | 35 |
| Median (95% Confidence Interval) [Months] |
5.72
|
6.87
|
7.59
|
6.44
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Axitinib + FOLFIRI, Bevacizumab + FOLFIRI |
|---|---|---|
| Comments | Differences in PFS between treatment arms was analyzed by 1-sided log rank test, stratified for Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8268 |
| Comments | One-sided log-rank test at alpha = 0.15 significance level was used. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.273 | |
| Confidence Interval |
(2-Sided) 95% 0.769 to 2.108 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Axitinib + FOLFOX, Bevacizumab + FOLFOX |
|---|---|---|
| Comments | Differences in PFS between treatment arms was analyzed by 1-sided log rank test, stratified for ECOG performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5498 |
| Comments | One-sided log-rank test at alpha = 0.15 significance level was used. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.041 | |
| Confidence Interval |
(2-Sided) 95% 0.553 to 1.041 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| Description | Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). |
| Time Frame | Baseline until death or up to 1 year after the randomization of last participant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized. |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Measure Participants | 49 | 51 | 36 | 35 |
| Median (95% Confidence Interval) [Months] |
12.9
|
15.7
|
17.1
|
14.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Axitinib + FOLFIRI, Bevacizumab + FOLFIRI |
|---|---|---|
| Comments | Differences in OS between treatment arms was analyzed by 1-sided log rank test, stratified for ECOG performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8828 |
| Comments | One-sided log-rank test at alpha = 0.15 significance level was used. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.355 | |
| Confidence Interval |
(2-Sided) 95% 0.820 to 2.238 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Axitinib + FOLFOX, Bevacizumab + FOLFOX |
|---|---|---|
| Comments | Differences in OS between treatment arms was analyzed by 1-sided log rank test, stratified for ECOG performance status (0 versus 1) and prior treatment with bevacizumab (yes versus no). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1159 |
| Comments | One-sided log-rank test at alpha = 0.15 significance level was used. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.689 | |
| Confidence Interval |
(2-Sided) 95% 0.373 to 1.273 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Objective Response (OR) |
|---|---|
| Description | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are 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 until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized. |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Measure Participants | 49 | 51 | 36 | 35 |
| Number (95% Confidence Interval) [Percentage of participants] |
24.5
50%
|
23.5
46.1%
|
19.4
53.9%
|
20.0
57.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Axitinib + FOLFIRI, Bevacizumab + FOLFIRI |
|---|---|---|
| Comments | One-sided Pearson chi square test at alpha = 0.15 significance level was used. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4552 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1 | |
| Confidence Interval |
(2-Sided) 95% -15.8 to 17.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Axitinib + FOLFOX, Bevacizumab + FOLFOX |
|---|---|---|
| Comments | One-sided Pearson chi square test at alpha = 0.15 significance level was used. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5235 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -19.1 to 18.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DR) |
|---|---|
| Description | Time in months 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 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Time Frame | Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| DR was calculated for the subgroup of participants from the ITT set, with a confirmed objective tumor response (CR or PR). |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Measure Participants | 12 | 12 | 7 | 7 |
| Median (95% Confidence Interval) [Months] |
7.52
|
12.29
|
10.15
|
10.94
|
| Title | Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal |
|---|---|
| Description | Symptom severity score is comprised of average of 14 MDASI-D core items (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling and diarrhea) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last week; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome. Total average score range: 0 to 10. |
| Time Frame | Baseline, Day 1 of cycles 2- 5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure and 'n' is number of participants analyzed at specific time point for each treatment arm respectively. |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Measure Participants | 39 | 46 | 35 | 33 |
| Baseline (n=39,46,35,33) |
2.1
|
1.8
|
1.9
|
2.0
|
| Change at Cycle 2/Day 1 (n=35, 39, 34,28) |
0.6
|
0.5
|
0.7
|
0.0
|
| Change at Cycle 3/Day 1 (n=36,36,33,26) |
0.8
|
0.2
|
0.3
|
0.2
|
| Change at Cycle 4/Day 1 (n=29,37,32,25) |
0.8
|
0.0
|
0.5
|
0.5
|
| Change at Cycle 5/Day 1 (n=28,29,24,24) |
0.5
|
0.1
|
0.9
|
0.4
|
| Change at Cycle 7/Day 1 (n=26,31,22,20) |
0.7
|
0.0
|
0.6
|
0.2
|
| Change at Cycle 9/Day 1 (n=19,26,19,17) |
1.1
|
-0.2
|
0.6
|
0.8
|
| Change at Cycle 11/Day 1 (n=15,24,16,15) |
1.0
|
0.1
|
1.0
|
0.1
|
| Change at Cycle 13/Day 1 (n=13,19,15,10) |
1.0
|
0.1
|
0.9
|
0.8
|
| Change at Cycle 15/Day 1 (n=7,17,12,8) |
0.8
|
0.2
|
0.5
|
1.0
|
| Change at Cycle 17/Day 1 (n=6,11,11,7) |
2.0
|
0.4
|
0.9
|
1.7
|
| Change at Cycle 19/Day 1 (n=6,10,9,5) |
1.3
|
0.5
|
0.8
|
1.4
|
| Change at Cycle 21/Day 1 (n=6,9,7,4) |
1.1
|
0.5
|
0.9
|
1.6
|
| Change at Cycle 23/Day 1 (n=5,7,6,4) |
2.6
|
-0.3
|
0.4
|
1.0
|
| Change at Cycle 25/Day 1 (n=5,7,6,3) |
2.2
|
0.1
|
0.2
|
1.0
|
| Change at Cycle 27/Day 1 (n=2,7,3,3) |
2.3
|
0.4
|
0.3
|
1.1
|
| Change at Cycle 29/Day 1 (n=2,5,2,3) |
2.8
|
-0.2
|
-0.8
|
0.9
|
| Change at Cycle 31/Day 1 (n=1,5,2,2) |
4.9
|
-0.4
|
-0.3
|
0.9
|
| Change at Cycle 33/Day 1 (n=1,3,2,1) |
5.0
|
-0.6
|
-0.8
|
0.5
|
| Change at Cycle 35/Day 1 (n=0,4,1,1) |
NA
|
-0.4
|
0.4
|
2.4
|
| Change at Cycle 37/Day 1 (n=0,4,0,1) |
NA
|
-0.5
|
NA
|
1.0
|
| Change at Cycle 39/Day 1 (n=0,2,0,1) |
NA
|
-0.4
|
NA
|
1.0
|
| Change at Cycle 41/Day 1 (n=0,2,0,1) |
NA
|
-0.3
|
NA
|
1.4
|
| Change at Cycle 43/Day 1 (n=0,1,0,1) |
NA
|
-0.4
|
NA
|
2.0
|
| Change at Cycle 45/Day 1 (n=0,0,0,1 ) |
NA
|
NA
|
NA
|
2.2
|
| Change at Cycle 47/Day 1 (n=0,1,0,0) |
NA
|
-0.4
|
NA
|
NA
|
| Change at Cycle 49/Day 1 (n=0,1,0,0) |
NA
|
-0.5
|
NA
|
NA
|
| Change at Cycle 51/Day 1 (n=0,1,0,0) |
NA
|
-0.4
|
NA
|
NA
|
| Change at Cycle 53/Day 1 (n=0,1,0,0) |
NA
|
-0.4
|
NA
|
NA
|
| Change at Cycle 55/Day 1 (n=0,1,0,0) |
NA
|
-0.3
|
NA
|
NA
|
| Change at Cycle 57/Day 1 (n=0,1,0,0) |
NA
|
-0.3
|
NA
|
NA
|
| Change at Cycle 59/Day 1 (n=0,1,0,0) |
NA
|
-0.3
|
NA
|
NA
|
| Change at Cycle 61/Day 1 (n=0,1,0,0) |
NA
|
-0.2
|
NA
|
NA
|
| Change at Cycle 63/Day 1 (n=0,0,0,0) |
NA
|
NA
|
NA
|
NA
|
| Change at Cycle 65/Day 1 (n=0,1,0,0) |
NA
|
-0.4
|
NA
|
NA
|
| Change at end of treatment (n=21,29,27,22) |
0.7
|
0.5
|
1.3
|
0.9
|
| Title | Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal |
|---|---|
| Description | Symptom Interference score is comprised of the average of 6 items on feeling or function from the MDASI-D core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last week; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome. Total average score range: 0 to 10. |
| Time Frame | Baseline, Day 1 of cycle 2-5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure and 'n' is number of participants analyzed at specific time point for each treatment arm respectively. |
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX |
|---|---|---|---|---|
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. |
| Measure Participants | 39 | 46 | 35 | 33 |
| Baseline (n=39,46,35,33) |
2.1
|
1.7
|
2.4
|
2.8
|
| Change at Cycle 2/Day 1 (n=35, 39, 34, 28) |
0.8
|
0.9
|
0.1
|
-0.5
|
| Change at Cycle 3/Day 1 (n=36,36,33,26) |
1.3
|
0.3
|
0.3
|
-0.2
|
| Change at Cycle 4/Day 1 (n=29,37,32,25) |
0.8
|
-0.2
|
0.2
|
0.5
|
| Change at Cycle 5/Day 1 (n=28,29,24,24) |
1.0
|
0.4
|
0.8
|
0.3
|
| Change at Cycle 7/Day 1 (n=26,30,22,20) |
0.7
|
0.4
|
0.4
|
0.0
|
| Change at Cycle 9/Day 1 (n=18,25,19,17) |
1.1
|
0.3
|
0.6
|
0.3
|
| Change at Cycle 11/Day 1 (n=15,24,16,15) |
1.0
|
0.3
|
0.8
|
-0.2
|
| Change at Cycle 13/Day 1 (n=13,19,15,10) |
1.1
|
0.7
|
1.3
|
0.7
|
| Change at Cycle 15/Day 1 (n=7,17,12,8) |
2.3
|
0.9
|
-0.1
|
1.3
|
| Change at Cycle 17/Day 1 (n=6,11,11,7) |
2.4
|
0.7
|
0.7
|
2.1
|
| Change at Cycle 19/Day 1 (n=6,10,9,5) |
2.1
|
0.8
|
0.3
|
2.4
|
| Change at Cycle 21/Day 1 (n=6,9,7,4) |
1.7
|
1.0
|
0.4
|
2.1
|
| Change at Cycle 23/Day 1 (n=5,7,6,4) |
2.2
|
-0.3
|
0.9
|
1.4
|
| Change at Cycle 25/Day 1 (n=5,7,6,3) |
1.6
|
0.5
|
-0.6
|
1.4
|
| Change at Cycle 27/Day 1 (n=2,7,3,3) |
1.6
|
0.9
|
-1.6
|
1.3
|
| Change at Cycle 29/Day 1 (n=2,5,2,3) |
3.2
|
0.0
|
-1.3
|
1.3
|
| Change at Cycle 31/Day 1 (n=1,5,2,2) |
4.5
|
-0.5
|
-0.1
|
1.2
|
| Change at Cycle 33/Day 1 (n=1,3,2,1) |
4.5
|
-0.2
|
-0.8
|
0.3
|
| Change at Cycle 35/Day 1 (n=0,4,1,1 ) |
NA
|
-0.3
|
-1.2
|
3.3
|
| Change at Cycle 37/Day 1 (n=0,4,0,1) |
NA
|
-0.4
|
NA
|
1.3
|
| Change at Cycle 39/Day 1 (n=0,2,0,1) |
NA
|
-0.3
|
NA
|
2.0
|
| Change at Cycle 41/Day 1 (n=0,2,0,1) |
NA
|
-0.2
|
NA
|
1.5
|
| Change at Cycle 43/Day 1 (n=0,1,0,1) |
NA
|
-0.3
|
NA
|
1.8
|
| Change at Cycle 45/Day 1 (n=0,0,0,1 ) |
NA
|
NA
|
NA
|
2.5
|
| Change at Cycle 47/Day 1 (n=0,1,0,0) |
NA
|
-0.2
|
NA
|
NA
|
| Change at Cycle 49/Day 1 (n=0,1,0,0) |
NA
|
-0.3
|
NA
|
NA
|
| Change at Cycle 51/Day 1 (n=0,1,0,0) |
NA
|
-0.3
|
NA
|
NA
|
| Change at Cycle 53/Day 1 (n=0,1,0,0) |
NA
|
-0.2
|
NA
|
NA
|
| Change at Cycle 55/Day 1 (n=0,1,0,0) |
NA
|
-0.3
|
NA
|
NA
|
| Change at Cycle 57/Day 1 (n=0,1,0,0) |
NA
|
0.0
|
NA
|
NA
|
| Change at Cycle 59/Day 1 (n=0,1,0,0) |
NA
|
-0.2
|
NA
|
NA
|
| Change at Cycle 61/Day 1 (n=0,1,0,0) |
NA
|
0.0
|
NA
|
NA
|
| Change at Cycle 63/Day 1 (n=0,0,0,0) |
NA
|
NA
|
NA
|
NA
|
| Change at Cycle 65/Day 1 (n=0,1,0,0) |
NA
|
-0.2
|
NA
|
NA
|
| Change at end of treatment (n=21,29,26,21) |
1.3
|
1.0
|
1.5
|
1.2
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||
| Arm/Group Title | Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX | ||||
| Arm/Group Description | Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m^2 (or levo-leucovarin [l-LV] 200 mg /m^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m^2 90 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m^2 120 minutes IV infusion, concurrently with LV 400 mg/m^2 (or l-LV 200 mg /m^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m^2 IV bolus injection and a subsequent 5-FU 2400 mg/m^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle. | ||||
All Cause Mortality |
||||||||
| Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/46 (37%) | 9/51 (17.6%) | 11/36 (30.6%) | 5/35 (14.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Febrile neutropenia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Neutropenia | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Otosalpingitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Abdominal pain upper | 0/46 (0%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Colonic obstruction | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Diarrhoea | 3/46 (6.5%) | 2/51 (3.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Gastrointestinal haemorrhage | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Haematochezia | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Ileal ulcer | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Ileus | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Nausea | 2/46 (4.3%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Oesophagitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Rectal perforation | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Stomatitis | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vomiting | 1/46 (2.2%) | 2/51 (3.9%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Anal inflammation | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Subileus | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Haemorrhagic ascites | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Gastrointestinal ulcer | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 2/46 (4.3%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Fatigue | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Performance status decreased | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| General physical health deterioration | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Disease progression | 2/46 (4.3%) | 3/51 (5.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 2/46 (4.3%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hepatic mass | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Bile duct stone | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| Cellulitis pharyngeal | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Escherichia sepsis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Pneumonia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Sepsis | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Anal abscess | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Lung infection | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Lumbar vertebral fracture | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 4/46 (8.7%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypovolaemia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Nervous system disorders | ||||||||
| Cerebral haemorrhage | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Headache | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Peripheral sensory neuropathy | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal failure acute | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Hypoxia | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Pneumothorax | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Pulmonary embolism | 2/46 (4.3%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Axitinib + FOLFIRI | Bevacizumab + FOLFIRI | Axitinib + FOLFOX | Bevacizumab + FOLFOX | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 45/46 (97.8%) | 51/51 (100%) | 35/36 (97.2%) | 33/35 (94.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 6/46 (13%) | 11/51 (21.6%) | 4/36 (11.1%) | 5/35 (14.3%) | ||||
| Coagulopathy | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Febrile neutropenia | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Leukopenia | 6/46 (13%) | 6/51 (11.8%) | 5/36 (13.9%) | 2/35 (5.7%) | ||||
| Lymphopenia | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Neutropenia | 20/46 (43.5%) | 27/51 (52.9%) | 20/36 (55.6%) | 10/35 (28.6%) | ||||
| Thrombocytopenia | 3/46 (6.5%) | 4/51 (7.8%) | 8/36 (22.2%) | 5/35 (14.3%) | ||||
| Cardiac disorders | ||||||||
| Cardiac failure congestive | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Left ventricular dysfunction | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Tachycardia | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear discomfort | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Ear disorder | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Ear pain | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| External ear inflammation | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hyperacusis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Otosalpingitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Tinnitus | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Vertigo | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypothyroidism | 7/46 (15.2%) | 0/51 (0%) | 9/36 (25%) | 1/35 (2.9%) | ||||
| Eye disorders | ||||||||
| Age-related macular degeneration | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Asthenopia | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Cataract | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Conjunctival oedema | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Conjunctivitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Dry eye | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Eye discharge | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Eye haemorrhage | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Eye irritation | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Eye pain | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Eye pruritus | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Lacrimation increased | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Mydriasis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Vision blurred | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Visual impairment | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Abdominal distension | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Abdominal pain | 12/46 (26.1%) | 11/51 (21.6%) | 7/36 (19.4%) | 9/35 (25.7%) | ||||
| Abdominal pain lower | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Abdominal pain upper | 5/46 (10.9%) | 6/51 (11.8%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Anal fissure | 2/46 (4.3%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Anal haemorrhage | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Anal inflammation | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Anorectal discomfort | 0/46 (0%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Ascites | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Chapped lips | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Cheilitis | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Constipation | 7/46 (15.2%) | 16/51 (31.4%) | 3/36 (8.3%) | 10/35 (28.6%) | ||||
| Defaecation urgency | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Dental discomfort | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Diarrhoea | 32/46 (69.6%) | 25/51 (49%) | 15/36 (41.7%) | 11/35 (31.4%) | ||||
| Dry mouth | 3/46 (6.5%) | 1/51 (2%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Dyspepsia | 7/46 (15.2%) | 5/51 (9.8%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Dysphagia | 2/46 (4.3%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Enteritis | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Epigastric discomfort | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Eructation | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Faecal incontinence | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Faeces discoloured | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Flatulence | 1/46 (2.2%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Gastritis | 3/46 (6.5%) | 2/51 (3.9%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Gastrointestinal toxicity | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Gastrooesophageal reflux disease | 1/46 (2.2%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gingival pain | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Gingivitis | 3/46 (6.5%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Haemorrhoidal haemorrhage | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Haemorrhoids | 4/46 (8.7%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hernial eventration | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Intestinal obstruction | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Large intestinal haemorrhage | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Lip ulceration | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Mouth ulceration | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Nausea | 27/46 (58.7%) | 30/51 (58.8%) | 18/36 (50%) | 16/35 (45.7%) | ||||
| Odynophagia | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Oesophagitis | 3/46 (6.5%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Oral pain | 2/46 (4.3%) | 1/51 (2%) | 2/36 (5.6%) | 0/35 (0%) | ||||
| Painful defaecation | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Periodontitis | 0/46 (0%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Peristalsis visible | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Proctalgia | 6/46 (13%) | 2/51 (3.9%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Proctitis | 2/46 (4.3%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Rectal fissure | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Rectal haemorrhage | 4/46 (8.7%) | 3/51 (5.9%) | 0/36 (0%) | 3/35 (8.6%) | ||||
| Rectal tenesmus | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Stomatitis | 11/46 (23.9%) | 7/51 (13.7%) | 9/36 (25%) | 7/35 (20%) | ||||
| Subileus | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Tooth erosion | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Toothache | 0/46 (0%) | 3/51 (5.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Vomiting | 22/46 (47.8%) | 18/51 (35.3%) | 12/36 (33.3%) | 3/35 (8.6%) | ||||
| General disorders | ||||||||
| Asthenia | 13/46 (28.3%) | 11/51 (21.6%) | 6/36 (16.7%) | 6/35 (17.1%) | ||||
| Chest discomfort | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Chest pain | 1/46 (2.2%) | 3/51 (5.9%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Chills | 2/46 (4.3%) | 1/51 (2%) | 2/36 (5.6%) | 2/35 (5.7%) | ||||
| Device occlusion | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Fatigue | 21/46 (45.7%) | 18/51 (35.3%) | 12/36 (33.3%) | 9/35 (25.7%) | ||||
| Implant site haematoma | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Influenza like illness | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Infusion site extravasation | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Injection site reaction | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Mucosal dryness | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Mucosal inflammation | 7/46 (15.2%) | 11/51 (21.6%) | 4/36 (11.1%) | 3/35 (8.6%) | ||||
| Oedema | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Oedema peripheral | 7/46 (15.2%) | 2/51 (3.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Pain | 0/46 (0%) | 1/51 (2%) | 3/36 (8.3%) | 1/35 (2.9%) | ||||
| Performance status decreased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Pyrexia | 5/46 (10.9%) | 7/51 (13.7%) | 5/36 (13.9%) | 3/35 (8.6%) | ||||
| Temperature intolerance | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Thrombosis in device | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholangitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hepatic function abnormal | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hepatic pain | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hyperbilirubinaemia | 3/46 (6.5%) | 1/51 (2%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Hyperplastic cholecystopathy | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Jaundice | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Jaundice cholestatic | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Portal vein thrombosis | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Immune system disorders | ||||||||
| Drug hypersensitivity | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypersensitivity | 0/46 (0%) | 1/51 (2%) | 5/36 (13.9%) | 1/35 (2.9%) | ||||
| Seasonal allergy | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| Anal abscess | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Bronchitis | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Clostridial infection | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Clostridium difficile colitis | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Colostomy infection | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Cystitis | 0/46 (0%) | 2/51 (3.9%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Device related infection | 1/46 (2.2%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Ear infection | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gastroenteritis | 2/46 (4.3%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Herpes simplex | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Herpes zoster | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hordeolum | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Infected sebaceous cyst | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Infection | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Influenza | 0/46 (0%) | 2/51 (3.9%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Laryngitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Lung infection | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Nasopharyngitis | 3/46 (6.5%) | 5/51 (9.8%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Oral candidiasis | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Oral herpes | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Pelvic abscess | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Pharyngitis | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Pneumonia | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Respiratory tract infection | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Rhinitis | 0/46 (0%) | 3/51 (5.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Septic shock | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Sinusitis | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Tonsillitis | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Tooth abscess | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Upper respiratory tract infection | 1/46 (2.2%) | 3/51 (5.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Urinary tract infection | 3/46 (6.5%) | 3/51 (5.9%) | 2/36 (5.6%) | 1/35 (2.9%) | ||||
| Viral upper respiratory tract infection | 2/46 (4.3%) | 3/51 (5.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Anal injury | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Contusion | 0/46 (0%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Excoriation | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Face injury | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Post procedural haemorrhage | 0/46 (0%) | 2/51 (3.9%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Scapula fracture | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Sunburn | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Thermal burn | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Tooth fracture | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Upper limb fracture | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 3/35 (8.6%) | ||||
| Alanine aminotransferase increased | 3/46 (6.5%) | 2/51 (3.9%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Aspartate aminotransferase | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 3/35 (8.6%) | ||||
| Aspartate aminotransferase increased | 2/46 (4.3%) | 2/51 (3.9%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Blood albumin decreased | 2/46 (4.3%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood alkaline phosphatase | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Blood alkaline phosphatase increased | 4/46 (8.7%) | 0/51 (0%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Blood bilirubin | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Blood bilirubin increased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood cholesterol increased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood creatine increased | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Blood creatinine | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Blood glucose increased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood lactate dehydrogenase increased | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Blood potassium decreased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood pressure increased | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood thyroid stimulating hormone increased | 4/46 (8.7%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Blood triglycerides increased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Breath sounds abnormal | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Carcinoembryonic antigen increased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Clostridium test positive | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gamma-glutamyltransferase increased | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| General physical condition normal | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Haemoglobin | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Haemoglobin decreased | 3/46 (6.5%) | 5/51 (9.8%) | 3/36 (8.3%) | 0/35 (0%) | ||||
| Lymphocyte count decreased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Neutrophil count | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Neutrophil count decreased | 4/46 (8.7%) | 3/51 (5.9%) | 3/36 (8.3%) | 2/35 (5.7%) | ||||
| Platelet count | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Platelet count decreased | 2/46 (4.3%) | 2/51 (3.9%) | 4/36 (11.1%) | 3/35 (8.6%) | ||||
| Visual field tests | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Weight decreased | 13/46 (28.3%) | 4/51 (7.8%) | 5/36 (13.9%) | 2/35 (5.7%) | ||||
| Weight increased | 0/46 (0%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| White blood cell count | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| White blood cell count decreased | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| White blood cell count increased | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 24/46 (52.2%) | 16/51 (31.4%) | 13/36 (36.1%) | 7/35 (20%) | ||||
| Dehydration | 7/46 (15.2%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypercalcaemia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hypercholesterolaemia | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Hyperglycaemia | 0/46 (0%) | 1/51 (2%) | 2/36 (5.6%) | 2/35 (5.7%) | ||||
| Hyperkalaemia | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 2/35 (5.7%) | ||||
| Hypoalbuminaemia | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypocalcaemia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hypoglycaemia | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypokalaemia | 4/46 (8.7%) | 3/51 (5.9%) | 3/36 (8.3%) | 2/35 (5.7%) | ||||
| Hypomagnesaemia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hyponatraemia | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Lactic acidosis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Metabolic acidosis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 2/46 (4.3%) | 1/51 (2%) | 2/36 (5.6%) | 3/35 (8.6%) | ||||
| Back pain | 3/46 (6.5%) | 6/51 (11.8%) | 2/36 (5.6%) | 2/35 (5.7%) | ||||
| Bone pain | 0/46 (0%) | 3/51 (5.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Flank pain | 2/46 (4.3%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Muscle atrophy | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Muscle contracture | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Muscle spasms | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Muscular weakness | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Musculoskeletal chest pain | 0/46 (0%) | 2/51 (3.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Musculoskeletal disorder | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Musculoskeletal pain | 2/46 (4.3%) | 2/51 (3.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Myalgia | 0/46 (0%) | 3/51 (5.9%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Neck pain | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Osteoarthritis | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Pain in extremity | 4/46 (8.7%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Spinal osteoarthritis | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Cancer pain | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Malignant pleural effusion | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Tumour haemorrhage | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Nervous system disorders | ||||||||
| Ageusia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Aphasia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Cerebral ischaemia | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Cholinergic syndrome | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Dizziness | 1/46 (2.2%) | 3/51 (5.9%) | 3/36 (8.3%) | 2/35 (5.7%) | ||||
| Dysaesthesia | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Dysgeusia | 5/46 (10.9%) | 1/51 (2%) | 3/36 (8.3%) | 4/35 (11.4%) | ||||
| Headache | 6/46 (13%) | 4/51 (7.8%) | 7/36 (19.4%) | 3/35 (8.6%) | ||||
| Hyperaesthesia | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Hypoaesthesia | 0/46 (0%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Myelopathy | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Neuropathy peripheral | 3/46 (6.5%) | 4/51 (7.8%) | 7/36 (19.4%) | 16/35 (45.7%) | ||||
| Paraesthesia | 0/46 (0%) | 2/51 (3.9%) | 4/36 (11.1%) | 3/35 (8.6%) | ||||
| Peripheral sensory neuropathy | 2/46 (4.3%) | 4/51 (7.8%) | 4/36 (11.1%) | 5/35 (14.3%) | ||||
| Somnolence | 0/46 (0%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Syncope | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Toxic neuropathy | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Transient ischaemic attack | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Anxiety | 3/46 (6.5%) | 3/51 (5.9%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Confusional state | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Delirium | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Depression | 5/46 (10.9%) | 3/51 (5.9%) | 2/36 (5.6%) | 0/35 (0%) | ||||
| Disorientation | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Insomnia | 3/46 (6.5%) | 2/51 (3.9%) | 2/36 (5.6%) | 3/35 (8.6%) | ||||
| Mood altered | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Nervousness | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Sleep disorder | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Bladder spasm | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Chromaturia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Dysuria | 2/46 (4.3%) | 1/51 (2%) | 3/36 (8.3%) | 4/35 (11.4%) | ||||
| Glycosuria | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Haematuria | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Hydronephrosis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Proteinuria | 8/46 (17.4%) | 5/51 (9.8%) | 2/36 (5.6%) | 3/35 (8.6%) | ||||
| Renal failure | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Ureteric obstruction | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Urinary incontinence | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Urinary retention | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Dysmenorrhoea | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Epididymitis | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Erectile dysfunction | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Gynaecomastia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Metrorrhagia | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Ovarian cyst | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Pelvic pain | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Uterine haemorrhage | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vaginal discharge | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Vaginal haemorrhage | 1/46 (2.2%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vulvovaginal pain | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Vulvovaginal pruritus | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchospasm | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Cough | 7/46 (15.2%) | 5/51 (9.8%) | 3/36 (8.3%) | 4/35 (11.4%) | ||||
| Dysphonia | 6/46 (13%) | 2/51 (3.9%) | 4/36 (11.1%) | 1/35 (2.9%) | ||||
| Dyspnoea | 8/46 (17.4%) | 3/51 (5.9%) | 4/36 (11.1%) | 0/35 (0%) | ||||
| Dyspnoea exertional | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Epistaxis | 11/46 (23.9%) | 15/51 (29.4%) | 4/36 (11.1%) | 5/35 (14.3%) | ||||
| Hiccups | 2/46 (4.3%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Lung disorder | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Nasal discomfort | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Nasal disorder | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Nasal ulcer | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Oropharyngeal discomfort | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Oropharyngeal pain | 2/46 (4.3%) | 5/51 (9.8%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Painful respiration | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Paranasal sinus hypersecretion | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Pneumonitis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Productive cough | 1/46 (2.2%) | 2/51 (3.9%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Pulmonary artery thrombosis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Pulmonary embolism | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Reflux laryngitis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Respiratory alkalosis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Rhinitis allergic | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Rhinorrhoea | 2/46 (4.3%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Sinus congestion | 0/46 (0%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Throat irritation | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Throat tightness | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Wheezing | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Alopecia | 6/46 (13%) | 12/51 (23.5%) | 2/36 (5.6%) | 0/35 (0%) | ||||
| Dermatitis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Dermatitis allergic | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 1/35 (2.9%) | ||||
| Dry skin | 2/46 (4.3%) | 0/51 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Eczema | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Erythema | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Facial wasting | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Hyperhidrosis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Nail disorder | 1/46 (2.2%) | 0/51 (0%) | 1/36 (2.8%) | 2/35 (5.7%) | ||||
| Nail toxicity | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Night sweats | 0/46 (0%) | 1/51 (2%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 8/46 (17.4%) | 3/51 (5.9%) | 4/36 (11.1%) | 2/35 (5.7%) | ||||
| Pruritus | 3/46 (6.5%) | 2/51 (3.9%) | 4/36 (11.1%) | 1/35 (2.9%) | ||||
| Rash | 5/46 (10.9%) | 2/51 (3.9%) | 3/36 (8.3%) | 1/35 (2.9%) | ||||
| Rash pruritic | 0/46 (0%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Skin discolouration | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Skin disorder | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Skin hyperpigmentation | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Skin lesion | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Skin toxicity | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Subcutaneous nodule | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Urticaria | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Embolism | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Embolism venous | 0/46 (0%) | 1/51 (2%) | 0/36 (0%) | 0/35 (0%) | ||||
| Flushing | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
| Haematoma | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Haemorrhage | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Hypertension | 17/46 (37%) | 8/51 (15.7%) | 24/36 (66.7%) | 6/35 (17.1%) | ||||
| Hypotension | 3/46 (6.5%) | 1/51 (2%) | 2/36 (5.6%) | 2/35 (5.7%) | ||||
| Pallor | 0/46 (0%) | 0/51 (0%) | 1/36 (2.8%) | 0/35 (0%) | ||||
| Phlebitis | 1/46 (2.2%) | 2/51 (3.9%) | 0/36 (0%) | 0/35 (0%) | ||||
| Thrombophlebitis superficial | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Thrombosis | 1/46 (2.2%) | 0/51 (0%) | 0/36 (0%) | 0/35 (0%) | ||||
| Vasculitis | 0/46 (0%) | 0/51 (0%) | 0/36 (0%) | 1/35 (2.9%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00615056
Other Study ID Numbers:
- A4061034
First Posted:
Feb 14, 2008
Last Update Posted:
Apr 19, 2013
Last Verified:
Apr 1, 2013