PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00115765
Collaborator
(none)
1,053
4
47
Study Details
Study Description
Brief Summary
The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1053 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer
Actual Study Start Date
:
Jun 1, 2005
Actual Primary Completion Date
:
May 31, 2007
Actual Study Completion Date
:
May 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Oxaliplatin and bevacizumab without panitumumab Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone. |
Drug: Oxaliplatin Based Chemotherapy
Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Names:
|
| Experimental: Irinotecan and bevacizumab plus panitumumab Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W |
Drug: Panitumumab
PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.
Other Names:
Drug: Irinotecan Based Chemotherapy
Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Names:
|
| Active Comparator: Irinotecan and bevacizumab without panitumumab Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
Drug: Irinotecan Based Chemotherapy
Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Names:
|
| Experimental: Oxaliplatin and bevacizumab plus panitumumab Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W |
Drug: Oxaliplatin Based Chemotherapy
Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
Drug: Panitumumab
PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.
Other Names:
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (Oxaliplatin) [Overall study]
Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression
- Objective Tumor Response Through Week 12 (Irinotecan) [Overall Study]
Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum
Secondary Outcome Measures
- Overall Survival (Oxaliplatin) [Overall study]
Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin
- Objective Tumor Response Rate (Oxaliplatin) [Overall study]
Best overall response of complete or partial response within oxaliplatin stratum
- Time to Progression (Oxaliplatin) [Overall Study]
Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the oxaliplatin stratum
- Time to Treatment Failure (Oxaliplatin) [Overall study]
Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the oxaliplatin stratum.
- Overall Survival (Irinotecan) [Overall study]
Incidence of mortality from any cause in groups treated with Irinotecan. Incidence is provided in lieu of the median time to death since the median or its measure of dispersion was not estimable for at least one treatment arm.
- Progression-free Survival (Irinotecan) [Overall Study]
Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression
- Objective Tumor Response Rate (Irinotecan) [Overall Study]
Best overall response of complete or partial response within irinotecan stratum
- Time to Progression (Irinotecan) [Overall Study]
Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the irinotecan stratum
- Time to Treatment Failure (Irinotecan) [Overall Study]
Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the irinotecan stratum
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Adenocarcinoma of the colon or rectum
-
Metastatic colorectal cancer (mCRC)
-
Measurable disease per modified response evaluation criteria in solid tumors (RECIST) criteria
-
ECOG performance status of 0 or 1
-
Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or unstained slides of paraffin-embedded tissue
-
If history of other primary cancer, subject will be eligible only if she or he has:
-
Curatively resected non-melanomatous skin cancer;
-
Curatively treated cervical carcinoma in situ;
-
Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 5 years.
-
Adequate hematologic data as follows:
-
Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 cells/L;
-
Platelet count greater than or equal to 100 x 10^9/L;
-
Hemoglobin greater than or equal to 9.0 g/dL. - Adequate renal function:
-
Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN);
-
Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then excretion of less than or equal to 1000 mg of protein per day as determined by 24-hour urine collection).
-
Adequate hepatic function:
-
Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
-
Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
-
Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
-
Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and date an IRB-approved informed consent form
-
Before any study-specific procedure, the appropriate written informed consent must be obtained.
Exclusion Criteria:
-
Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease
-
Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before randomization - Radiotherapy within 14 days before randomization
-
Elective and/or planned major surgical procedure to be performed during the course of this trial (surgery that arises as needed or necessary during the course of the study, not agreed a priori, will not make the subject ineligible)
-
Major surgery within 28 days before randomization
-
Central nervous system metastases
-
History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan
-
Clinically significant ascites
-
Preexisting bleeding diathesis or coagulopathy or the need for full-dose anticoagulation
-
Any of the following within 1 year before randomization:
-
Myocardial infarction;
-
Unstable angina;
-
Symptomatic congestive heart failure;
-
Serious uncontrolled cardiac arrhythmia;
-
Cerebrovascular accident or transient ischemic attack;
-
Gastrointestinal ulcer or hemorrhage;
-
Hemoptysis;
-
Pulmonary embolism;
-
Deep vein thrombosis, or other significant thromboembolic event.
-
Regular use of non-steroidal anti-inflammatory agents
-
Female subject of childbearing potential, not abstinent, and not willing to use contraceptives during the course of the study and for 6 months following the last dose of first-line treatment
-
Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization
-
Male subject, not abstinent, and not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of first-line treatment
-
Subject known to be human immunodeficiency virus (HIV) positive
-
Subject allergic to panitumumab or any components of panitumumab formulation
-
History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
-
Subject unwilling or unable to comply with study requirements
-
Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00115765
Other Study ID Numbers:
- 20040249
First Posted:
Jun 27, 2005
Last Update Posted:
Oct 17, 2018
Last Verified:
Sep 1, 2018
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled from 10 March 2005 through 19 October 2006. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Irinotecan and Bevacizumab Without Panitumumab | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab | Irinotecan and Bevacizumab Plus Panitumumab |
|---|---|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W alone | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W |
| Period Title: Overall Study | ||||
| STARTED | 115 | 413 | 410 | 115 |
| COMPLETED | 80 | 313 | 289 | 84 |
| NOT COMPLETED | 35 | 100 | 121 | 31 |
Baseline Characteristics
| Arm/Group Title | Oxaliplatin and Bevacizumab Without Panitumumab | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab | Oxaliplatin and Bevacizumab Plus Panitumumab | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Total of all reporting groups |
| Overall Participants | 410 | 115 | 115 | 413 | 1053 |
| Age (Year) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Year] |
61.0
(11.9)
|
59.4
(11.7)
|
57.8
(12.0)
|
60.8
(11.7)
|
60.4
(11.8)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
172
42%
|
59
51.3%
|
44
38.3%
|
180
43.6%
|
455
43.2%
|
| Male |
238
58%
|
56
48.7%
|
71
61.7%
|
233
56.4%
|
598
56.8%
|
| Race/Ethnicity, Customized (Participant) [Number] | |||||
| White or Caucasian |
330
|
86
|
85
|
343
|
844
|
| Black or African American |
41
|
18
|
16
|
35
|
110
|
| Hispanic or Latino |
25
|
6
|
14
|
25
|
70
|
| Asian |
10
|
2
|
0
|
10
|
22
|
| Japanese |
2
|
0
|
0
|
0
|
2
|
| American Indian or Alaska Native |
1
|
2
|
0
|
0
|
3
|
| Native Hawaiian or Other Pacific Islander |
1
|
0
|
0
|
0
|
1
|
| Other |
0
|
1
|
0
|
0
|
1
|
| ECOG Score (Participant) [Number] | |||||
| 0 |
239
|
68
|
74
|
253
|
634
|
| 1 |
171
|
47
|
41
|
160
|
419
|
| Number of Metastatic Organs (Participant) [Number] | |||||
| None |
0
|
0
|
0
|
1
|
1
|
| 1 |
199
|
46
|
53
|
204
|
502
|
| >1 |
211
|
69
|
62
|
208
|
550
|
| Primary Site of Disease (Participant) [Number] | |||||
| Colon |
326
|
92
|
95
|
322
|
835
|
| Rectal |
84
|
23
|
20
|
91
|
218
|
| Prior adjuvant chemotherapy (Participant) [Number] | |||||
| Yes |
77
|
38
|
36
|
80
|
231
|
| No |
333
|
77
|
79
|
333
|
822
|
Outcome Measures
| Title | Progression-Free Survival (Oxaliplatin) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression |
| Time Frame | Overall study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 413 | 410 |
| Median (95% Confidence Interval) [Month] |
10.0
|
11.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.011 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Model covariates were ECOG status, prior chemotherapy, metastatic organs, disease site, oxaliplatin dose < 85 mg/m2, and oxaliplatin dose > 100 mg/m2 | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
() 95% 1.06 to 1.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (Oxaliplatin) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin |
| Time Frame | Overall study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 413 | 410 |
| Median (95% Confidence Interval) [Month] |
19.4
|
24.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Model covariates were ECOG status, prior chemotherapy, metastatic organs, disease site, oxaliplatin dose < 85 mg/m2, and oxaliplatin dose > 100 mg/m2 | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.43 | |
| Confidence Interval |
() 95% 1.11 to 1.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Tumor Response Rate (Oxaliplatin) |
|---|---|
| Description | Best overall response of complete or partial response within oxaliplatin stratum |
| Time Frame | Overall study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 413 | 410 |
| Number [Participant] |
190
|
196
|
| Title | Time to Progression (Oxaliplatin) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the oxaliplatin stratum |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 413 | 410 |
| Median (95% Confidence Interval) [Month] |
10.8
|
11.4
|
| Title | Time to Treatment Failure (Oxaliplatin) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the oxaliplatin stratum. |
| Time Frame | Overall study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 413 | 410 |
| Median (95% Confidence Interval) [Month] |
5.7
|
5.9
|
| Title | Objective Tumor Response Through Week 12 (Irinotecan) |
|---|---|
| Description | Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 115 | 115 |
| Number [Participant] |
29
|
27
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.738 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Model covariates were ECOG status, prior adjuvant chemotherapy, number of metastatic organs, and primary disease site | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.11 | |
| Confidence Interval |
() 95% 0.60 to 2.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (Irinotecan) |
|---|---|
| Description | Incidence of mortality from any cause in groups treated with Irinotecan. Incidence is provided in lieu of the median time to death since the median or its measure of dispersion was not estimable for at least one treatment arm. |
| Time Frame | Overall study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 115 | 115 |
| Number [Participant] |
26
|
18
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.257 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Model covariates were ECOG status, prior adjuvant chemotherapy, number of metastatic organs, and primary disease site | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.42 | |
| Confidence Interval |
() 95% 0.77 to 2.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-free Survival (Irinotecan) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 115 | 115 |
| Median (95% Confidence Interval) [Month] |
10.1
|
11.7
|
| Title | Progression-free Survival (Wild-type KRAS) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression in groups treated with oxaliplatin and having a wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as wild-type, who were treated with oxaliplatin |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 201 | 203 |
| Median (95% Confidence Interval) [Month] |
9.8
|
11.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.36 | |
| Confidence Interval |
() 95% 1.04 to 1.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-free Survival (Mutant KRAS) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression in groups treated with oxaliplatin and having a mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as mutant, who were treated with oxaliplatin |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 135 | 125 |
| Median (95% Confidence Interval) [Month] |
10.4
|
11.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.25 | |
| Confidence Interval |
() 95% 0.91 to 1.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (Wild-type KRAS) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin and having a wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS). Since the measure of dispersion could not be estimated for at least one treatment arm, participant incidence is provided in lieu of the median |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as wild-type, who were treated with oxaliplatin |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 201 | 203 |
| Number [Participant] |
71
|
46
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.89 | |
| Confidence Interval |
() 95% 1.30 to 2.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (Mutant KRAS) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin and having a mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS). Since the measure of dispersion could not be estimated for at least one treatment arm, participant incidence is provided in lieu of the median. |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as mutant, who were treated with oxaliplatin |
| Arm/Group Title | Oxaliplatin and Bevacizumab Plus Panitumumab | Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 135 | 125 |
| Number [Participant] |
47
|
45
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.02 | |
| Confidence Interval |
() 95% 0.67 to 1.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Tumor Response Rate (Wild-type KRAS) |
|---|---|
| Description | Best overall response of complete or partial response in participants treated with irinotecan and having a wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as wild-type, who were treated with irinotecan |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 57 | 58 |
| Number [Participant] |
31
|
28
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.28 | |
| Confidence Interval |
() 95% 0.61 to 2.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Tumor Response Rate (Mutant KRAS) |
|---|---|
| Description | Best overall response of complete or partial response in participants treated with irinotecan and having a mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as mutant, who were treated with irinotecan |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 47 | 39 |
| Number [Participant] |
14
|
15
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oxaliplatin and Bevacizumab Plus Panitumumab, Oxaliplatin and Bevacizumab Without Panitumumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.68 | |
| Confidence Interval |
() 95% 0.28 to 1.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Tumor Response Rate (Irinotecan) |
|---|---|
| Description | Best overall response of complete or partial response within irinotecan stratum |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 115 | 115 |
| Number [Participant] |
49
|
46
|
| Title | Time to Progression (Irinotecan) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the irinotecan stratum |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 115 | 115 |
| Median (95% Confidence Interval) [Month] |
11.1
|
11.9
|
| Title | Time to Treatment Failure (Irinotecan) |
|---|---|
| Description | Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the irinotecan stratum |
| Time Frame | Overall Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-Treat |
| Arm/Group Title | Irinotecan and Bevacizumab Plus Panitumumab | Irinotecan and Bevacizumab Without Panitumumab |
|---|---|---|
| Arm/Group Description | Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W | Irinotecan-based chemotherapy and Bevacizumab Q2W alone |
| Measure Participants | 115 | 115 |
| Median (95% Confidence Interval) [Month] |
6.6
|
6.0
|
Adverse Events
| Time Frame | First dose through maximum of safety FU or 30 days after last dose | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. | |||
| Arm/Group Title | Panit. Plus Bevacizumab With Chemotherapy | Bevacizumab With Chemotherapy | ||
| Arm/Group Description | ||||
All Cause Mortality |
||||
| Panit. Plus Bevacizumab With Chemotherapy | Bevacizumab With Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Panit. Plus Bevacizumab With Chemotherapy | Bevacizumab With Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 306/518 (59.1%) | 188/510 (36.9%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 0/518 (0%) | 4/510 (0.8%) | ||
| FEBRILE NEUTROPENIA | 20/518 (3.9%) | 9/510 (1.8%) | ||
| GRANULOCYTOPENIA | 0/518 (0%) | 1/510 (0.2%) | ||
| HAEMOLYSIS | 0/518 (0%) | 1/510 (0.2%) | ||
| LEUKOCYTOSIS | 0/518 (0%) | 1/510 (0.2%) | ||
| LEUKOPENIA | 3/518 (0.6%) | 2/510 (0.4%) | ||
| NEUTROPENIA | 9/518 (1.7%) | 8/510 (1.6%) | ||
| PANCYTOPENIA | 1/518 (0.2%) | 1/510 (0.2%) | ||
| SPLENIC INFARCTION | 1/518 (0.2%) | 0/510 (0%) | ||
| THROMBOCYTOPENIA | 6/518 (1.2%) | 5/510 (1%) | ||
| Cardiac disorders | ||||
| ANGINA PECTORIS | 3/518 (0.6%) | 5/510 (1%) | ||
| ANGINA UNSTABLE | 1/518 (0.2%) | 0/510 (0%) | ||
| ARRHYTHMIA | 2/518 (0.4%) | 2/510 (0.4%) | ||
| ARTERIOSPASM CORONARY | 0/518 (0%) | 1/510 (0.2%) | ||
| ATRIAL FIBRILLATION | 3/518 (0.6%) | 2/510 (0.4%) | ||
| ATRIAL FLUTTER | 0/518 (0%) | 1/510 (0.2%) | ||
| CARDIAC ARREST | 3/518 (0.6%) | 1/510 (0.2%) | ||
| CARDIAC FAILURE | 0/518 (0%) | 1/510 (0.2%) | ||
| CARDIAC FAILURE CONGESTIVE | 3/518 (0.6%) | 4/510 (0.8%) | ||
| CARDIO-RESPIRATORY ARREST | 2/518 (0.4%) | 1/510 (0.2%) | ||
| CARDIOMYOPATHY | 1/518 (0.2%) | 0/510 (0%) | ||
| CORONARY ARTERY DISEASE | 1/518 (0.2%) | 2/510 (0.4%) | ||
| CORONARY ARTERY OCCLUSION | 1/518 (0.2%) | 0/510 (0%) | ||
| MYOCARDIAL INFARCTION | 1/518 (0.2%) | 4/510 (0.8%) | ||
| MYOCARDIAL ISCHAEMIA | 1/518 (0.2%) | 0/510 (0%) | ||
| PALPITATIONS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PERICARDIAL EFFUSION | 2/518 (0.4%) | 0/510 (0%) | ||
| SINUS TACHYCARDIA | 2/518 (0.4%) | 0/510 (0%) | ||
| SUPRAVENTRICULAR TACHYCARDIA | 2/518 (0.4%) | 1/510 (0.2%) | ||
| TACHYCARDIA | 2/518 (0.4%) | 1/510 (0.2%) | ||
| VENTRICULAR FIBRILLATION | 1/518 (0.2%) | 0/510 (0%) | ||
| Eye disorders | ||||
| DIPLOPIA | 1/518 (0.2%) | 0/510 (0%) | ||
| ECTROPION | 1/518 (0.2%) | 0/510 (0%) | ||
| EYELID DISORDER | 1/518 (0.2%) | 0/510 (0%) | ||
| EYELID FUNCTION DISORDER | 1/518 (0.2%) | 0/510 (0%) | ||
| VISUAL DISTURBANCE | 0/518 (0%) | 1/510 (0.2%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL ADHESIONS | 1/518 (0.2%) | 0/510 (0%) | ||
| ABDOMINAL DISTENSION | 1/518 (0.2%) | 0/510 (0%) | ||
| ABDOMINAL PAIN | 23/518 (4.4%) | 17/510 (3.3%) | ||
| ABDOMINAL PAIN LOWER | 3/518 (0.6%) | 0/510 (0%) | ||
| ABDOMINAL PAIN UPPER | 0/518 (0%) | 1/510 (0.2%) | ||
| ANAL FISTULA | 0/518 (0%) | 2/510 (0.4%) | ||
| ANO-RECTAL ULCER | 0/518 (0%) | 1/510 (0.2%) | ||
| ASCITES | 1/518 (0.2%) | 0/510 (0%) | ||
| CAECITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| COLITIS | 4/518 (0.8%) | 2/510 (0.4%) | ||
| COLITIS ISCHAEMIC | 1/518 (0.2%) | 1/510 (0.2%) | ||
| COLITIS ULCERATIVE | 1/518 (0.2%) | 0/510 (0%) | ||
| COLONIC OBSTRUCTION | 1/518 (0.2%) | 0/510 (0%) | ||
| CONSTIPATION | 4/518 (0.8%) | 1/510 (0.2%) | ||
| CROHN'S DISEASE | 0/518 (0%) | 1/510 (0.2%) | ||
| DIARRHOEA | 63/518 (12.2%) | 15/510 (2.9%) | ||
| DIARRHOEA HAEMORRHAGIC | 1/518 (0.2%) | 0/510 (0%) | ||
| DIVERTICULAR PERFORATION | 1/518 (0.2%) | 0/510 (0%) | ||
| DUODENAL PERFORATION | 1/518 (0.2%) | 0/510 (0%) | ||
| DUODENAL ULCER PERFORATION | 0/518 (0%) | 1/510 (0.2%) | ||
| DUODENITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| DYSPEPSIA | 0/518 (0%) | 2/510 (0.4%) | ||
| DYSPHAGIA | 1/518 (0.2%) | 1/510 (0.2%) | ||
| ENTERITIS | 5/518 (1%) | 0/510 (0%) | ||
| ENTEROCOLITIS | 2/518 (0.4%) | 0/510 (0%) | ||
| ENTEROCUTANEOUS FISTULA | 1/518 (0.2%) | 0/510 (0%) | ||
| ENTEROVESICAL FISTULA | 0/518 (0%) | 1/510 (0.2%) | ||
| EROSIVE OESOPHAGITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| FAECALOMA | 1/518 (0.2%) | 0/510 (0%) | ||
| GASTRIC ULCER | 1/518 (0.2%) | 1/510 (0.2%) | ||
| GASTRIC ULCER PERFORATION | 0/518 (0%) | 1/510 (0.2%) | ||
| GASTROINTESTINAL FISTULA | 1/518 (0.2%) | 0/510 (0%) | ||
| GASTROINTESTINAL HAEMORRHAGE | 7/518 (1.4%) | 4/510 (0.8%) | ||
| GASTROINTESTINAL INFLAMMATION | 0/518 (0%) | 1/510 (0.2%) | ||
| GASTROINTESTINAL OBSTRUCTION | 2/518 (0.4%) | 0/510 (0%) | ||
| GASTROINTESTINAL PAIN | 1/518 (0.2%) | 0/510 (0%) | ||
| GASTROINTESTINAL PERFORATION | 2/518 (0.4%) | 0/510 (0%) | ||
| GASTROINTESTINAL TOXICITY | 1/518 (0.2%) | 0/510 (0%) | ||
| GASTROINTESTINAL ULCER | 1/518 (0.2%) | 0/510 (0%) | ||
| GASTROOESOPHAGEAL REFLUX DISEASE | 3/518 (0.6%) | 0/510 (0%) | ||
| HAEMATEMESIS | 1/518 (0.2%) | 0/510 (0%) | ||
| HAEMATOCHEZIA | 1/518 (0.2%) | 0/510 (0%) | ||
| HAEMORRHOIDS | 1/518 (0.2%) | 0/510 (0%) | ||
| ILEUS | 7/518 (1.4%) | 3/510 (0.6%) | ||
| ILEUS PARALYTIC | 1/518 (0.2%) | 0/510 (0%) | ||
| INTESTINAL OBSTRUCTION | 7/518 (1.4%) | 5/510 (1%) | ||
| INTESTINAL PERFORATION | 4/518 (0.8%) | 0/510 (0%) | ||
| LARGE INTESTINAL OBSTRUCTION | 1/518 (0.2%) | 0/510 (0%) | ||
| LARGE INTESTINE PERFORATION | 3/518 (0.6%) | 1/510 (0.2%) | ||
| MALLORY-WEISS SYNDROME | 0/518 (0%) | 1/510 (0.2%) | ||
| NAUSEA | 24/518 (4.6%) | 7/510 (1.4%) | ||
| OESOPHAGITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| PANCREATITIS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PANCREATITIS ACUTE | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PERITONITIS | 2/518 (0.4%) | 0/510 (0%) | ||
| PNEUMOPERITONEUM | 1/518 (0.2%) | 0/510 (0%) | ||
| PROCTALGIA | 0/518 (0%) | 2/510 (0.4%) | ||
| RECTAL HAEMORRHAGE | 2/518 (0.4%) | 2/510 (0.4%) | ||
| RETROPERITONEAL HAEMORRHAGE | 0/518 (0%) | 1/510 (0.2%) | ||
| SMALL INTESTINAL OBSTRUCTION | 12/518 (2.3%) | 8/510 (1.6%) | ||
| STOMATITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| VOMITING | 27/518 (5.2%) | 10/510 (2%) | ||
| General disorders | ||||
| ASTHENIA | 10/518 (1.9%) | 4/510 (0.8%) | ||
| CATHETER RELATED COMPLICATION | 2/518 (0.4%) | 1/510 (0.2%) | ||
| CHEST PAIN | 1/518 (0.2%) | 1/510 (0.2%) | ||
| CHILLS | 2/518 (0.4%) | 1/510 (0.2%) | ||
| DISEASE PROGRESSION | 0/518 (0%) | 1/510 (0.2%) | ||
| FATIGUE | 2/518 (0.4%) | 2/510 (0.4%) | ||
| GENERAL PHYSICAL HEALTH DETERIORATION | 1/518 (0.2%) | 1/510 (0.2%) | ||
| INFUSION RELATED REACTION | 0/518 (0%) | 1/510 (0.2%) | ||
| MUCOSAL INFLAMMATION | 6/518 (1.2%) | 1/510 (0.2%) | ||
| MULTI-ORGAN FAILURE | 1/518 (0.2%) | 0/510 (0%) | ||
| NON-CARDIAC CHEST PAIN | 4/518 (0.8%) | 2/510 (0.4%) | ||
| OEDEMA PERIPHERAL | 1/518 (0.2%) | 0/510 (0%) | ||
| PAIN | 4/518 (0.8%) | 0/510 (0%) | ||
| PELVIC MASS | 1/518 (0.2%) | 0/510 (0%) | ||
| PNEUMATOSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| PYREXIA | 16/518 (3.1%) | 9/510 (1.8%) | ||
| SWELLING | 1/518 (0.2%) | 0/510 (0%) | ||
| SYSTEMIC INFLAMMATORY RESPONSE SYNDROME | 2/518 (0.4%) | 0/510 (0%) | ||
| ULCER | 1/518 (0.2%) | 0/510 (0%) | ||
| Hepatobiliary disorders | ||||
| CHOLECYSTITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| CHOLELITHIASIS | 0/518 (0%) | 1/510 (0.2%) | ||
| GALLBLADDER FISTULA | 1/518 (0.2%) | 0/510 (0%) | ||
| HEPATIC FAILURE | 1/518 (0.2%) | 0/510 (0%) | ||
| HEPATIC LESION | 0/518 (0%) | 1/510 (0.2%) | ||
| JAUNDICE CHOLESTATIC | 0/518 (0%) | 1/510 (0.2%) | ||
| LIVER DISORDER | 0/518 (0%) | 1/510 (0.2%) | ||
| Immune system disorders | ||||
| ANAPHYLACTIC REACTION | 1/518 (0.2%) | 2/510 (0.4%) | ||
| DRUG HYPERSENSITIVITY | 2/518 (0.4%) | 1/510 (0.2%) | ||
| HYPERSENSITIVITY | 4/518 (0.8%) | 1/510 (0.2%) | ||
| Infections and infestations | ||||
| ABDOMINAL ABSCESS | 2/518 (0.4%) | 0/510 (0%) | ||
| ABDOMINAL INFECTION | 1/518 (0.2%) | 0/510 (0%) | ||
| ABSCESS | 2/518 (0.4%) | 0/510 (0%) | ||
| ACUTE SINUSITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| APPENDICITIS | 0/518 (0%) | 1/510 (0.2%) | ||
| BACTERAEMIA | 5/518 (1%) | 4/510 (0.8%) | ||
| BACTERIAL INFECTION | 1/518 (0.2%) | 0/510 (0%) | ||
| BACTERIAL SEPSIS | 2/518 (0.4%) | 0/510 (0%) | ||
| BRONCHITIS | 0/518 (0%) | 3/510 (0.6%) | ||
| CANDIDIASIS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| CATHETER RELATED INFECTION | 7/518 (1.4%) | 2/510 (0.4%) | ||
| CATHETER SEPSIS | 0/518 (0%) | 1/510 (0.2%) | ||
| CELLULITIS | 4/518 (0.8%) | 1/510 (0.2%) | ||
| CELLULITIS GANGRENOUS | 1/518 (0.2%) | 0/510 (0%) | ||
| CELLULITIS STAPHYLOCOCCAL | 2/518 (0.4%) | 0/510 (0%) | ||
| CLOSTRIDIAL INFECTION | 3/518 (0.6%) | 1/510 (0.2%) | ||
| CLOSTRIDIUM DIFFICILE COLITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| CYSTITIS KLEBSIELLA | 0/518 (0%) | 1/510 (0.2%) | ||
| DEVICE RELATED INFECTION | 1/518 (0.2%) | 1/510 (0.2%) | ||
| DIVERTICULITIS | 0/518 (0%) | 1/510 (0.2%) | ||
| ESCHERICHIA BACTERAEMIA | 1/518 (0.2%) | 0/510 (0%) | ||
| EXTRADURAL ABSCESS | 1/518 (0.2%) | 0/510 (0%) | ||
| FUNGAEMIA | 0/518 (0%) | 1/510 (0.2%) | ||
| FUNGAL INFECTION | 1/518 (0.2%) | 0/510 (0%) | ||
| FUNGAL SEPSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| FUNGAL SKIN INFECTION | 1/518 (0.2%) | 1/510 (0.2%) | ||
| GASTROENTERITIS | 4/518 (0.8%) | 3/510 (0.6%) | ||
| GASTROENTERITIS VIRAL | 1/518 (0.2%) | 0/510 (0%) | ||
| HERPES SIMPLEX | 1/518 (0.2%) | 0/510 (0%) | ||
| INFECTION | 2/518 (0.4%) | 1/510 (0.2%) | ||
| INTERTRIGO CANDIDA | 1/518 (0.2%) | 0/510 (0%) | ||
| INTERVERTEBRAL DISCITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| KIDNEY INFECTION | 1/518 (0.2%) | 0/510 (0%) | ||
| MEDIASTINITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| MENINGITIS CRYPTOCOCCAL | 0/518 (0%) | 1/510 (0.2%) | ||
| MUSCLE ABSCESS | 0/518 (0%) | 1/510 (0.2%) | ||
| NECROTISING FASCIITIS | 2/518 (0.4%) | 0/510 (0%) | ||
| NEUTROPENIC INFECTION | 1/518 (0.2%) | 0/510 (0%) | ||
| NEUTROPENIC SEPSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| OSTEOMYELITIS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PAROTITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| PELVIC ABSCESS | 2/518 (0.4%) | 0/510 (0%) | ||
| PERIRECTAL ABSCESS | 2/518 (0.4%) | 0/510 (0%) | ||
| PERITONEAL INFECTION | 1/518 (0.2%) | 0/510 (0%) | ||
| PERITONITIS BACTERIAL | 1/518 (0.2%) | 0/510 (0%) | ||
| PNEUMONIA | 3/518 (0.6%) | 9/510 (1.8%) | ||
| PNEUMONIA BACTERIAL | 1/518 (0.2%) | 0/510 (0%) | ||
| POSTOPERATIVE WOUND INFECTION | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PYELONEPHRITIS | 2/518 (0.4%) | 1/510 (0.2%) | ||
| RASH PUSTULAR | 1/518 (0.2%) | 0/510 (0%) | ||
| RECTAL ABSCESS | 0/518 (0%) | 1/510 (0.2%) | ||
| RETROPERITONEAL ABSCESS | 2/518 (0.4%) | 0/510 (0%) | ||
| SEPSIS | 16/518 (3.1%) | 8/510 (1.6%) | ||
| SEPTIC SHOCK | 2/518 (0.4%) | 3/510 (0.6%) | ||
| SINUSITIS | 0/518 (0%) | 1/510 (0.2%) | ||
| STAPHYLOCOCCAL BACTERAEMIA | 3/518 (0.6%) | 1/510 (0.2%) | ||
| STAPHYLOCOCCAL INFECTION | 1/518 (0.2%) | 1/510 (0.2%) | ||
| STREPTOCOCCAL BACTERAEMIA | 0/518 (0%) | 1/510 (0.2%) | ||
| TRACHEOBRONCHITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 0/518 (0%) | 1/510 (0.2%) | ||
| URINARY TRACT INFECTION | 7/518 (1.4%) | 2/510 (0.4%) | ||
| URINARY TRACT INFECTION FUNGAL | 1/518 (0.2%) | 0/510 (0%) | ||
| UROSEPSIS | 2/518 (0.4%) | 1/510 (0.2%) | ||
| WOUND INFECTION | 3/518 (0.6%) | 0/510 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| ANASTOMOTIC LEAK | 1/518 (0.2%) | 0/510 (0%) | ||
| ARTHROPOD BITE | 0/518 (0%) | 1/510 (0.2%) | ||
| CARBON MONOXIDE POISONING | 0/518 (0%) | 1/510 (0.2%) | ||
| CONTUSION | 2/518 (0.4%) | 0/510 (0%) | ||
| DRUG TOXICITY | 0/518 (0%) | 1/510 (0.2%) | ||
| FACIAL BONES FRACTURE | 1/518 (0.2%) | 0/510 (0%) | ||
| FALL | 0/518 (0%) | 1/510 (0.2%) | ||
| FOOT FRACTURE | 0/518 (0%) | 1/510 (0.2%) | ||
| GASTROINTESTINAL STOMA COMPLICATION | 0/518 (0%) | 1/510 (0.2%) | ||
| HIP FRACTURE | 3/518 (0.6%) | 0/510 (0%) | ||
| IMPLANTABLE DEFIBRILLATOR MALFUNCTION | 1/518 (0.2%) | 0/510 (0%) | ||
| POST PROCEDURAL HAEMORRHAGE | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PROCEDURAL PAIN | 1/518 (0.2%) | 0/510 (0%) | ||
| SUBDURAL HAEMATOMA | 0/518 (0%) | 2/510 (0.4%) | ||
| TIBIA FRACTURE | 0/518 (0%) | 1/510 (0.2%) | ||
| WOUND | 1/518 (0.2%) | 0/510 (0%) | ||
| WOUND DEHISCENCE | 1/518 (0.2%) | 1/510 (0.2%) | ||
| Investigations | ||||
| BLOOD AMYLASE INCREASED | 0/518 (0%) | 1/510 (0.2%) | ||
| BLOOD MAGNESIUM DECREASED | 0/518 (0%) | 1/510 (0.2%) | ||
| BLOOD POTASSIUM DECREASED | 1/518 (0.2%) | 0/510 (0%) | ||
| ELECTROCARDIOGRAM ABNORMAL | 1/518 (0.2%) | 0/510 (0%) | ||
| HAEMOGLOBIN INCREASED | 1/518 (0.2%) | 0/510 (0%) | ||
| LIPASE INCREASED | 0/518 (0%) | 1/510 (0.2%) | ||
| NEUTROPHIL COUNT DECREASED | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PLATELET COUNT DECREASED | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PROTHROMBIN TIME PROLONGED | 1/518 (0.2%) | 0/510 (0%) | ||
| WEIGHT DECREASED | 2/518 (0.4%) | 0/510 (0%) | ||
| Metabolism and nutrition disorders | ||||
| ACIDOSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| ANOREXIA | 5/518 (1%) | 1/510 (0.2%) | ||
| DECREASED APPETITE | 1/518 (0.2%) | 0/510 (0%) | ||
| DEHYDRATION | 72/518 (13.9%) | 21/510 (4.1%) | ||
| DIABETIC KETOACIDOSIS | 0/518 (0%) | 1/510 (0.2%) | ||
| ELECTROLYTE IMBALANCE | 2/518 (0.4%) | 1/510 (0.2%) | ||
| FAILURE TO THRIVE | 0/518 (0%) | 1/510 (0.2%) | ||
| GOUT | 0/518 (0%) | 1/510 (0.2%) | ||
| HYPERGLYCAEMIA | 2/518 (0.4%) | 0/510 (0%) | ||
| HYPERNATRAEMIA | 1/518 (0.2%) | 0/510 (0%) | ||
| HYPOCALCAEMIA | 2/518 (0.4%) | 0/510 (0%) | ||
| HYPOGLYCAEMIA | 1/518 (0.2%) | 1/510 (0.2%) | ||
| HYPOKALAEMIA | 12/518 (2.3%) | 4/510 (0.8%) | ||
| HYPOMAGNESAEMIA | 6/518 (1.2%) | 0/510 (0%) | ||
| HYPOVOLAEMIA | 3/518 (0.6%) | 1/510 (0.2%) | ||
| MALNUTRITION | 0/518 (0%) | 1/510 (0.2%) | ||
| METABOLIC ACIDOSIS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| BACK PAIN | 5/518 (1%) | 6/510 (1.2%) | ||
| FISTULA | 2/518 (0.4%) | 0/510 (0%) | ||
| INTERVERTEBRAL DISC DEGENERATION | 0/518 (0%) | 1/510 (0.2%) | ||
| INTERVERTEBRAL DISC PROTRUSION | 0/518 (0%) | 1/510 (0.2%) | ||
| MUSCLE SPASMS | 1/518 (0.2%) | 0/510 (0%) | ||
| MUSCULAR WEAKNESS | 3/518 (0.6%) | 0/510 (0%) | ||
| MUSCULOSKELETAL CHEST PAIN | 0/518 (0%) | 2/510 (0.4%) | ||
| NECK PAIN | 1/518 (0.2%) | 0/510 (0%) | ||
| PAIN IN EXTREMITY | 1/518 (0.2%) | 1/510 (0.2%) | ||
| SHOULDER PAIN | 2/518 (0.4%) | 0/510 (0%) | ||
| SOFT TISSUE NECROSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| CANCER PAIN | 1/518 (0.2%) | 0/510 (0%) | ||
| COLON CANCER | 12/518 (2.3%) | 4/510 (0.8%) | ||
| COLON CANCER METASTATIC | 9/518 (1.7%) | 2/510 (0.4%) | ||
| COLORECTAL CANCER | 1/518 (0.2%) | 2/510 (0.4%) | ||
| COLORECTAL CANCER METASTATIC | 1/518 (0.2%) | 0/510 (0%) | ||
| HEPATIC NEOPLASM MALIGNANT RECURRENT | 1/518 (0.2%) | 0/510 (0%) | ||
| METASTATIC NEOPLASM | 1/518 (0.2%) | 0/510 (0%) | ||
| Nervous system disorders | ||||
| APHASIA | 0/518 (0%) | 1/510 (0.2%) | ||
| CEREBRAL HAEMORRHAGE | 0/518 (0%) | 1/510 (0.2%) | ||
| CEREBRAL ISCHAEMIA | 1/518 (0.2%) | 0/510 (0%) | ||
| CEREBROVASCULAR ACCIDENT | 1/518 (0.2%) | 0/510 (0%) | ||
| CONVULSION | 5/518 (1%) | 1/510 (0.2%) | ||
| COORDINATION ABNORMAL | 1/518 (0.2%) | 0/510 (0%) | ||
| DIZZINESS | 3/518 (0.6%) | 4/510 (0.8%) | ||
| ENCEPHALOPATHY | 0/518 (0%) | 1/510 (0.2%) | ||
| GRAND MAL CONVULSION | 1/518 (0.2%) | 0/510 (0%) | ||
| HEADACHE | 3/518 (0.6%) | 3/510 (0.6%) | ||
| HYPERTENSIVE ENCEPHALOPATHY | 0/518 (0%) | 1/510 (0.2%) | ||
| LETHARGY | 1/518 (0.2%) | 0/510 (0%) | ||
| LOSS OF CONSCIOUSNESS | 0/518 (0%) | 1/510 (0.2%) | ||
| METABOLIC ENCEPHALOPATHY | 1/518 (0.2%) | 0/510 (0%) | ||
| NEUROPATHY | 1/518 (0.2%) | 0/510 (0%) | ||
| NEUROPATHY PERIPHERAL | 1/518 (0.2%) | 1/510 (0.2%) | ||
| RADICULOPATHY | 0/518 (0%) | 1/510 (0.2%) | ||
| SUBARACHNOID HAEMORRHAGE | 0/518 (0%) | 1/510 (0.2%) | ||
| SYNCOPE | 3/518 (0.6%) | 3/510 (0.6%) | ||
| TRANSIENT ISCHAEMIC ATTACK | 3/518 (0.6%) | 0/510 (0%) | ||
| Psychiatric disorders | ||||
| CONFUSIONAL STATE | 2/518 (0.4%) | 0/510 (0%) | ||
| DEPRESSION | 2/518 (0.4%) | 0/510 (0%) | ||
| MAJOR DEPRESSION | 1/518 (0.2%) | 0/510 (0%) | ||
| MENTAL STATUS CHANGES | 1/518 (0.2%) | 1/510 (0.2%) | ||
| PANIC ATTACK | 1/518 (0.2%) | 0/510 (0%) | ||
| SUICIDE ATTEMPT | 1/518 (0.2%) | 0/510 (0%) | ||
| Renal and urinary disorders | ||||
| CALCULUS URINARY | 0/518 (0%) | 1/510 (0.2%) | ||
| DYSURIA | 1/518 (0.2%) | 0/510 (0%) | ||
| FAECALURIA | 0/518 (0%) | 1/510 (0.2%) | ||
| HAEMATURIA | 1/518 (0.2%) | 1/510 (0.2%) | ||
| HYDRONEPHROSIS | 2/518 (0.4%) | 0/510 (0%) | ||
| NEPHROLITHIASIS | 2/518 (0.4%) | 0/510 (0%) | ||
| RENAL FAILURE | 6/518 (1.2%) | 2/510 (0.4%) | ||
| RENAL FAILURE ACUTE | 2/518 (0.4%) | 4/510 (0.8%) | ||
| URETERIC OBSTRUCTION | 1/518 (0.2%) | 0/510 (0%) | ||
| URETHRAL OBSTRUCTION | 1/518 (0.2%) | 0/510 (0%) | ||
| URINARY RETENTION | 1/518 (0.2%) | 0/510 (0%) | ||
| URINARY TRACT PAIN | 1/518 (0.2%) | 0/510 (0%) | ||
| VESICAL FISTULA | 1/518 (0.2%) | 0/510 (0%) | ||
| Reproductive system and breast disorders | ||||
| FEMALE GENITAL TRACT FISTULA | 1/518 (0.2%) | 2/510 (0.4%) | ||
| VULVAL DISORDER | 1/518 (0.2%) | 0/510 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| ACUTE RESPIRATORY DISTRESS SYNDROME | 3/518 (0.6%) | 0/510 (0%) | ||
| ACUTE RESPIRATORY FAILURE | 1/518 (0.2%) | 2/510 (0.4%) | ||
| BRONCHOSPASM | 1/518 (0.2%) | 0/510 (0%) | ||
| COUGH | 1/518 (0.2%) | 1/510 (0.2%) | ||
| DYSAESTHESIA PHARYNX | 0/518 (0%) | 1/510 (0.2%) | ||
| DYSPNOEA | 8/518 (1.5%) | 12/510 (2.4%) | ||
| DYSPNOEA EXACERBATED | 1/518 (0.2%) | 0/510 (0%) | ||
| EPISTAXIS | 2/518 (0.4%) | 0/510 (0%) | ||
| HAEMOPTYSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| HYPOXIA | 3/518 (0.6%) | 1/510 (0.2%) | ||
| PLATYPNOEA | 1/518 (0.2%) | 0/510 (0%) | ||
| PLEURAL EFFUSION | 3/518 (0.6%) | 1/510 (0.2%) | ||
| PNEUMONIA ASPIRATION | 2/518 (0.4%) | 0/510 (0%) | ||
| PNEUMOTHORAX | 0/518 (0%) | 2/510 (0.4%) | ||
| PULMONARY EMBOLISM | 35/518 (6.8%) | 17/510 (3.3%) | ||
| PULMONARY OEDEMA | 1/518 (0.2%) | 1/510 (0.2%) | ||
| RESPIRATORY DISTRESS | 2/518 (0.4%) | 1/510 (0.2%) | ||
| RESPIRATORY FAILURE | 1/518 (0.2%) | 1/510 (0.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| DERMATITIS | 1/518 (0.2%) | 0/510 (0%) | ||
| INTERTRIGO | 1/518 (0.2%) | 0/510 (0%) | ||
| PETECHIAE | 0/518 (0%) | 1/510 (0.2%) | ||
| PURPURA | 0/518 (0%) | 1/510 (0.2%) | ||
| RASH | 5/518 (1%) | 0/510 (0%) | ||
| SKIN REACTION | 1/518 (0.2%) | 0/510 (0%) | ||
| TELANGIECTASIA | 1/518 (0.2%) | 0/510 (0%) | ||
| Surgical and medical procedures | ||||
| COLECTOMY | 2/518 (0.4%) | 0/510 (0%) | ||
| CRYOTHERAPY | 0/518 (0%) | 1/510 (0.2%) | ||
| HEPATECTOMY | 14/518 (2.7%) | 6/510 (1.2%) | ||
| HEPATIC EMBOLISATION | 0/518 (0%) | 1/510 (0.2%) | ||
| HIGH FREQUENCY ABLATION | 2/518 (0.4%) | 1/510 (0.2%) | ||
| LESION EXCISION | 1/518 (0.2%) | 0/510 (0%) | ||
| LIVER OPERATION | 0/518 (0%) | 1/510 (0.2%) | ||
| LUNG NEOPLASM SURGERY | 0/518 (0%) | 1/510 (0.2%) | ||
| Vascular disorders | ||||
| ARTERIOSCLEROSIS | 1/518 (0.2%) | 0/510 (0%) | ||
| AXILLARY VEIN THROMBOSIS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| CIRCULATORY COLLAPSE | 1/518 (0.2%) | 0/510 (0%) | ||
| DEEP VEIN THROMBOSIS | 17/518 (3.3%) | 12/510 (2.4%) | ||
| EMBOLISM | 1/518 (0.2%) | 1/510 (0.2%) | ||
| HAEMATOMA | 2/518 (0.4%) | 2/510 (0.4%) | ||
| HAEMORRHAGE | 0/518 (0%) | 1/510 (0.2%) | ||
| HYPERTENSION | 4/518 (0.8%) | 5/510 (1%) | ||
| HYPOTENSION | 4/518 (0.8%) | 6/510 (1.2%) | ||
| JUGULAR VEIN THROMBOSIS | 1/518 (0.2%) | 1/510 (0.2%) | ||
| ORTHOSTATIC HYPOTENSION | 1/518 (0.2%) | 0/510 (0%) | ||
| SUBCLAVIAN VEIN THROMBOSIS | 2/518 (0.4%) | 2/510 (0.4%) | ||
| THROMBOSIS | 3/518 (0.6%) | 2/510 (0.4%) | ||
| VENA CAVA THROMBOSIS | 2/518 (0.4%) | 0/510 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Panit. Plus Bevacizumab With Chemotherapy | Bevacizumab With Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 516/518 (99.6%) | 505/510 (99%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 177/518 (34.2%) | 147/510 (28.8%) | ||
| LEUKOPENIA | 53/518 (10.2%) | 60/510 (11.8%) | ||
| NEUTROPENIA | 179/518 (34.6%) | 207/510 (40.6%) | ||
| THROMBOCYTOPENIA | 71/518 (13.7%) | 108/510 (21.2%) | ||
| Eye disorders | ||||
| CONJUNCTIVITIS | 31/518 (6%) | 6/510 (1.2%) | ||
| LACRIMATION INCREASED | 34/518 (6.6%) | 34/510 (6.7%) | ||
| VISION BLURRED | 29/518 (5.6%) | 22/510 (4.3%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 132/518 (25.5%) | 114/510 (22.4%) | ||
| ABDOMINAL PAIN UPPER | 48/518 (9.3%) | 38/510 (7.5%) | ||
| CONSTIPATION | 217/518 (41.9%) | 187/510 (36.7%) | ||
| DIARRHOEA | 385/518 (74.3%) | 350/510 (68.6%) | ||
| DRY MOUTH | 30/518 (5.8%) | 31/510 (6.1%) | ||
| DYSPEPSIA | 86/518 (16.6%) | 72/510 (14.1%) | ||
| DYSPHAGIA | 31/518 (6%) | 18/510 (3.5%) | ||
| FLATULENCE | 33/518 (6.4%) | 48/510 (9.4%) | ||
| GASTROOESOPHAGEAL REFLUX DISEASE | 35/518 (6.8%) | 40/510 (7.8%) | ||
| HAEMORRHOIDS | 41/518 (7.9%) | 49/510 (9.6%) | ||
| NAUSEA | 359/518 (69.3%) | 368/510 (72.2%) | ||
| ORAL PAIN | 46/518 (8.9%) | 40/510 (7.8%) | ||
| PROCTALGIA | 34/518 (6.6%) | 24/510 (4.7%) | ||
| RECTAL HAEMORRHAGE | 43/518 (8.3%) | 34/510 (6.7%) | ||
| STOMATITIS | 171/518 (33%) | 91/510 (17.8%) | ||
| VOMITING | 215/518 (41.5%) | 199/510 (39%) | ||
| General disorders | ||||
| ASTHENIA | 92/518 (17.8%) | 68/510 (13.3%) | ||
| CHILLS | 63/518 (12.2%) | 55/510 (10.8%) | ||
| FATIGUE | 354/518 (68.3%) | 371/510 (72.7%) | ||
| MUCOSAL INFLAMMATION | 159/518 (30.7%) | 104/510 (20.4%) | ||
| OEDEMA PERIPHERAL | 54/518 (10.4%) | 61/510 (12%) | ||
| PAIN | 38/518 (7.3%) | 39/510 (7.6%) | ||
| PYREXIA | 111/518 (21.4%) | 82/510 (16.1%) | ||
| TEMPERATURE INTOLERANCE | 65/518 (12.5%) | 99/510 (19.4%) | ||
| Infections and infestations | ||||
| PARONYCHIA | 51/518 (9.8%) | 0/510 (0%) | ||
| SINUSITIS | 26/518 (5%) | 35/510 (6.9%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 26/518 (5%) | 38/510 (7.5%) | ||
| URINARY TRACT INFECTION | 72/518 (13.9%) | 47/510 (9.2%) | ||
| Investigations | ||||
| NEUTROPHIL COUNT DECREASED | 25/518 (4.8%) | 32/510 (6.3%) | ||
| WEIGHT DECREASED | 166/518 (32%) | 107/510 (21%) | ||
| Metabolism and nutrition disorders | ||||
| ANOREXIA | 211/518 (40.7%) | 155/510 (30.4%) | ||
| DECREASED APPETITE | 50/518 (9.7%) | 51/510 (10%) | ||
| DEHYDRATION | 129/518 (24.9%) | 72/510 (14.1%) | ||
| HYPERGLYCAEMIA | 43/518 (8.3%) | 34/510 (6.7%) | ||
| HYPOCALCAEMIA | 35/518 (6.8%) | 9/510 (1.8%) | ||
| HYPOKALAEMIA | 172/518 (33.2%) | 73/510 (14.3%) | ||
| HYPOMAGNESAEMIA | 148/518 (28.6%) | 14/510 (2.7%) | ||
| HYPONATRAEMIA | 26/518 (5%) | 12/510 (2.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 60/518 (11.6%) | 71/510 (13.9%) | ||
| BACK PAIN | 71/518 (13.7%) | 74/510 (14.5%) | ||
| MUSCULOSKELETAL CHEST PAIN | 30/518 (5.8%) | 31/510 (6.1%) | ||
| MYALGIA | 29/518 (5.6%) | 46/510 (9%) | ||
| PAIN IN EXTREMITY | 54/518 (10.4%) | 49/510 (9.6%) | ||
| SHOULDER PAIN | 33/518 (6.4%) | 40/510 (7.8%) | ||
| Nervous system disorders | ||||
| DIZZINESS | 107/518 (20.7%) | 93/510 (18.2%) | ||
| DYSGEUSIA | 95/518 (18.3%) | 97/510 (19%) | ||
| HEADACHE | 95/518 (18.3%) | 113/510 (22.2%) | ||
| HYPOAESTHESIA | 33/518 (6.4%) | 41/510 (8%) | ||
| NEUROPATHY | 98/518 (18.9%) | 115/510 (22.5%) | ||
| NEUROPATHY PERIPHERAL | 94/518 (18.1%) | 106/510 (20.8%) | ||
| PARAESTHESIA | 82/518 (15.8%) | 104/510 (20.4%) | ||
| PERIPHERAL SENSORY NEUROPATHY | 64/518 (12.4%) | 85/510 (16.7%) | ||
| Psychiatric disorders | ||||
| ANXIETY | 61/518 (11.8%) | 65/510 (12.7%) | ||
| DEPRESSION | 91/518 (17.6%) | 68/510 (13.3%) | ||
| INSOMNIA | 122/518 (23.6%) | 126/510 (24.7%) | ||
| Renal and urinary disorders | ||||
| HAEMATURIA | 29/518 (5.6%) | 23/510 (4.5%) | ||
| PROTEINURIA | 46/518 (8.9%) | 46/510 (9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| COUGH | 106/518 (20.5%) | 97/510 (19%) | ||
| DYSPHONIA | 31/518 (6%) | 31/510 (6.1%) | ||
| DYSPNOEA | 126/518 (24.3%) | 100/510 (19.6%) | ||
| EPISTAXIS | 146/518 (28.2%) | 164/510 (32.2%) | ||
| HICCUPS | 27/518 (5.2%) | 38/510 (7.5%) | ||
| PHARYNGOLARYNGEAL PAIN | 71/518 (13.7%) | 57/510 (11.2%) | ||
| RHINORRHOEA | 26/518 (5%) | 25/510 (4.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| ALOPECIA | 111/518 (21.4%) | 86/510 (16.9%) | ||
| DERMATITIS ACNEIFORM | 179/518 (34.6%) | 7/510 (1.4%) | ||
| DRY SKIN | 143/518 (27.6%) | 38/510 (7.5%) | ||
| ERYTHEMA | 75/518 (14.5%) | 24/510 (4.7%) | ||
| EXFOLIATIVE RASH | 33/518 (6.4%) | 2/510 (0.4%) | ||
| NAIL DISORDER | 41/518 (7.9%) | 17/510 (3.3%) | ||
| PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME | 52/518 (10%) | 31/510 (6.1%) | ||
| PRURITUS | 141/518 (27.2%) | 33/510 (6.5%) | ||
| RASH | 331/518 (63.9%) | 71/510 (13.9%) | ||
| SKIN FISSURES | 72/518 (13.9%) | 10/510 (2%) | ||
| SKIN HYPERPIGMENTATION | 13/518 (2.5%) | 26/510 (5.1%) | ||
| SKIN ULCER | 32/518 (6.2%) | 5/510 (1%) | ||
| Vascular disorders | ||||
| DEEP VEIN THROMBOSIS | 26/518 (5%) | 25/510 (4.9%) | ||
| HYPERTENSION | 86/518 (16.6%) | 107/510 (21%) | ||
| HYPOTENSION | 49/518 (9.5%) | 24/510 (4.7%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00115765
Other Study ID Numbers:
- 20040249
First Posted:
Jun 27, 2005
Last Update Posted:
Oct 17, 2018
Last Verified:
Sep 1, 2018