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Trial record 62 of 126 for:    colon cancer AND Rectal | ( Map: New Jersey, United States )

PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study

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ClinicalTrials.gov Identifier: NCT00911170
Recruitment Status : Completed
First Posted : June 1, 2009
Results First Posted : January 7, 2014
Last Update Posted : December 29, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Supportive Care
Conditions Cancer
Colon Cancer
Colorectal Cancer
Fever
Locally Advanced
Metastatic Colorectal Cancer
Neutropenia
Rectal Cancer
Interventions Drug: Pegfilgrastim
Drug: Placebo
Biological: Bevacizumab
Drug: Standard Chemotherapy
Enrollment 847
Recruitment Details The first participant was enrolled into the study on 03 November 2009 and the last participant on 03 January 2012.
Pre-assignment Details This study included a a study treatment period (approximately 8 weeks), and a long-term follow-up period (up to 36 months after the last participant was enrolled).
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle, plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4). During the long-term follow-up period, further chemotherapy and/or biologic agents (for example, bevacizumab) were to continue at the discretion of the treating physician. Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4). During the long-term follow-up period, further chemotherapy and/or biologic agents (for example, bevacizumab) were to continue at the discretion of the treating physician.
Period Title: Treatment Period
Started 424 423
Received Chemotherapy 423 [1] 422 [1]
Received Bevacizumab 423 420
Received Investigational Product 422 [2] 419
Completed 397 [3] 386 [3]
Not Completed 27 37
Reason Not Completed
Randomized in error             1             1
Ineligibility determined             1             3
Protocol deviation             1             2
Adverse Event             9             10
Withdrawal by Subject             4             4
Disease progression             0             2
Physician Decision             5             5
Lost to Follow-up             0             1
Death             6             9
[1]
Primary Analysis Set
[2]
Includes one participant who received pegfilgrastim in error.
[3]
Completed 4 cycles of treatment including chemotherapy, bevacizumab and investigational product.
Period Title: Long Term Follow-Up
Started 423 [1] 422 [1]
Completed 0 [2] 0 [2]
Not Completed 423 422
Reason Not Completed
Continuing in study             274             269
Withdrawal by Subject             20             21
Physician Decision             5             4
Lost to Follow-up             8             7
Death             116             121
[1]
Participants who received treatment in the Treatment Period
[2]
As of the data cut-off date of 8 June 2012
Arm/Group Title Placebo Pegfilgrastim Total
Hide Arm/Group Description Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4). Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4). Total of all reporting groups
Overall Number of Baseline Participants 423 422 845
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 423 participants 422 participants 845 participants
60.7  (10.7) 60.6  (10.4) 60.6  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 423 participants 422 participants 845 participants
Female
159
  37.6%
174
  41.2%
333
  39.4%
Male
264
  62.4%
248
  58.8%
512
  60.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 423 participants 422 participants 845 participants
American Indian or Alaska Native 0 1 1
Asian 3 2 5
Black or African American 6 4 10
Hispanic or Latino 8 11 19
Japanese 0 2 2
Native Hawaiian or Other Pacific Islander 2 0 2
White 404 402 806
Chemotherapy Regimen  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 423 participants 422 participants 845 participants
FOLFOX 207 207 414
FOLFIRI 216 215 431
Region   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 423 participants 422 participants 845 participants
North America 79 77 156
Rest of World 344 345 689
[1]
Measure Description: North America (Canada and the US) and the Rest of World (Australia, Belgium, Bulgaria, Czech Republic, France, Hungary, Ireland, Italy, Latvia, Mexico, Poland, Romania, Russian Federation, Slovakia, and Ukraine)
Disease Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 423 participants 422 participants 845 participants
Locally Advanced 18 18 36
Metastatic 405 404 809
Primary Tumor Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 423 participants 422 participants 845 participants
Colon 284 290 574
Rectum 139 132 271
1.Primary Outcome
Title Percentage of Participants With Grade 3/4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
Hide Description Grade 3/4 febrile neutropenia (FN) is defined as: • A temperature ≥ 38.0°C (≥ 100.4°F) and absolute neutrophil count (ANC) < 1.0 × 10^9/L, where ANC was measured the same day or within ± 1 calendar day of a temperature ≥ 38.0°C (≥ 100.4°F), or • An ANC < 1.0 × 10^9/L in combination with: – documented sepsis or infection, OR – neutropenia-related hospitalization where ANC was measured the same day or within ± 1 calendar day. Participants monitored their oral temperatures and maintained diaries to record their temperature twice per day: once in the morning and once in the evening, as well as whenever they suspect they had fever throughout the first 4 cycles of chemotherapy treatment.
Time Frame Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis set which included all participants with a signed informed consent, and who were randomized and received at least 1 dose of protocol-specified study treatment (chemotherapy, bevacizumab, or investigational product).
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.7
(3.7 to 8.3)
2.4
(1.1 to 4.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments The primary hypothesis was that the percentage of participants treated with study chemotherapy and bevacizumab who experience grade 3/4 febrile neutropenia (FN) would be lower in participants randomized to the pegfilgrastim arm compared to placebo arm. The study was designed to have at least 90% power at the 2-sided 0.05 significance level to detect a 6% difference in incidence of grade 3/4 FN from 9% to 3%, which is approximately a 66.7% relative reduction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value is adjusted for the randomization stratification factors (chemotherapy regimen, geographic region, disease stage).
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.19 to 0.86
Estimation Comments Odds ratio adjusted for the randomization stratification factors. An OR < 1.0 indicates a lower event rate for the pegfilgrastim arm relative to the placebo arm.
2.Secondary Outcome
Title Overall Survival
Hide Description Median time from randomization to date of death caclulated using the Kaplan-Meier method. Participants were censored on the date of last contact (i.e., the date the participant was last known to be alive) if they were not known to have died.
Time Frame From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Median (95% Confidence Interval)
Unit of Measure: months
24.6 [1] 
(21.3 to NA)
21.8
(18.5 to 25.6)
[1]
Could not be estimated due to the low number of events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.704
Comments [Not Specified]
Method Log Rank
Comments P-values based on the log-rank test statistic from the Kaplan-Meier survival analysis stratified by the 3 randomization factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.81 to 1.36
Estimation Comments Based on Cox proportional Hazard model stratified by chemotherapy regimen, region and disease status. A HR< 1.0 indicates a lower average event rate and a longer survival time for the pegfilgrastim arm relative to the placebo arm.
3.Secondary Outcome
Title Progression Free Survival
Hide Description Time from randomization to date of radiological disease progression or death from any cause, whichever event occurs first, calculated using the Kaplan-Meier method. Participants without either event by the analysis data cutoff date were censored on the date of their last evaluable disease assessment. Disease progression based on the investigator’s assessment of radiographic scans using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Clinical progression without radiological assessment was not be considered a disease progression in this analysis. Progression defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Median (95% Confidence Interval)
Unit of Measure: months
10.1
(9.3 to 11.1)
9.7
(9.2 to 10.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.552
Comments [Not Specified]
Method Log Rank
Comments P-values are based on the log-rank test statistic from the Kaplan-Meier survival analysis stratified by the 3 randomization factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.88 to 1.26
Estimation Comments Based on Cox proportional Hazard model stratified by chemotherapy regimen, region and disease status. A HR< 1.0 indicates a lower average event rate and a longer survival time for the pegfilgrastim arm relative to the placebo arm.
4.Secondary Outcome
Title Time to Progression
Hide Description Time from randomization to date of radiological disease progression calculated using the Kaplan-Meier method. Participants without progression were censored on the date of their last radiographic tumor assessment. Disease progression based on the investigator’s assessment of scans using the RECIST v1.1. Clinical progression without radiological assessment was not considered a disease progression. Progression defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(10.0 to 11.8)
10.8
(9.5 to 11.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.502
Comments [Not Specified]
Method Log Rank
Comments P-values are based on the log-rank test statistic from the Kaplan-Meier survival analysis stratified by the 3 randomization factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.88 to 1.29
Estimation Comments Based on Cox proportional Hazard model stratified by chemotherapy regimen, region and disease status. A HR< 1.0 indicates a lower average event rate and a longer survival time for the pegfilgrastim arm relative to the placebo arm.
5.Secondary Outcome
Title Percentage of Participants With an Objective Response
Hide Description The percentage of participants with a complete response (CR) or partial response (PR) defined by the RECIST v1.1 criteria at any time during the study. Response was be determined by the investigator’s assessment of radiographic scans. CR: Disappearance of all non-nodal target lesions and the disappearance of all non-nodal non-target lesions, and no new lesions. All nodal lesions must have reduction of short axis to < 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters and no new lesions and/or unequivocal progression of existing non-target lesions, or, the disappearance of all non-nodal target lesions with persistence of one or more non-target lesion(s).
Time Frame From randomization to the data cut-off date of 8 June 2012. Median time on study was 11.6 months and the maximum was 27.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set participants with measurable disease at Baseline.
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 420 420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
56.7
(51.8 to 61.5)
58.1
(53.2 to 62.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.683
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value is from the Cochran Mantel Haenszel (CMH) test adjusting for the randomization stratification factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.81 to 1.39
Estimation Comments Odds ratio (OR) adjusted for the randomization stratification factors. An OR > 1.0 indicates a higher event rate for the pegfilgrastim arm relative to the placebo arm.
6.Secondary Outcome
Title Percentage of Participants With Grade 4 Febrile Neutropenia Across the First 4 Cycles of Chemotherapy
Hide Description

Grade 4 febrile neutropenia (FN) is defined as:

  • A temperature ≥ 38.0ºC (≥ 100.4ºF) and absolute neutrophil count (ANC) < 0.5 × 10^9/L, where ANC is measured the same day or within +/- 1 calendar day of a temperature ≥ 38.0ºC (≥ 100.4ºF), or
  • An ANC <0.5 × 10^9/L in combination with:

    • Documented sepsis or infection, OR
    • Neutropenia-related hospitalization where ANC is measured the same day or within +/- 1 calendar day.
Time Frame Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.5
(2.0 to 5.8)
2.4
(1.1 to 4.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.312
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value is from the Cochran Mantel Haenszel (CMH) test adjusting for the randomization stratification factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.66
Confidence Interval 95%
0.29 to 1.49
Estimation Comments Odds ratio (OR) adjusted for the randomization stratification factors. An OR < 1.0 indicates a lower event rate for the pegfilgrastim arm relative to the placebo arm.
7.Secondary Outcome
Title Percentage of Participants With Grade 3/4 Neutropenia Across the First 4 Cycles of Chemotherapy
Hide Description Grade 3/4 severe neutropenia is defined as neutropenia with absolute neutrophil count (ANC) <1.0 x 10^9/L.
Time Frame Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.0
(13.6 to 20.9)
3.6
(2.0 to 5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value is from the Cochran Mantel Haenszel (CMH) test adjusting for the randomization stratification factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.18
Confidence Interval 95%
0.10 to 0.32
Estimation Comments Odds ratio (OR) adjusted for the randomization stratification factors. An OR < 1.0 indicates a lower event rate for the pegfilgrastim arm relative to the placebo arm.
8.Secondary Outcome
Title Percentage of Participants With Grade 4 Neutropenia Across the First 4 Cycles of Chemotherapy
Hide Description Grade 4 severe neutropenia is defined as neutropenia with absolute neutrophil count (ANC) <0.5 x 10^9/L.
Time Frame Approximately 2 months duration (Daily for 4 cycles of treatment; 2 weeks per cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 423 422
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.3
(5.8 to 11.3)
2.4
(1.1 to 4.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pegfilgrastim
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value is from the Cochran Mantel Haenszel (CMH) test adjusting for the randomization stratification factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
0.13 to 0.56
Estimation Comments Odds ratio (OR) adjusted for the randomization stratification factors. An OR < 1.0 indicates a lower event rate for the pegfilgrastim arm relative to the placebo arm.
9.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description A serious adverse event (SAE) is defined as an adverse event that - is fatal; - is life threatening (places the participant at immediate risk of death); - requires inpatient hospitalization or prolongation of existing hospitalization; - results in persistent or significant disability/incapacity; - is a congenital anomaly/birth defect; - other significant medical hazard. AEs were assessed for severity according to National Cancer Institute, Common Terminology Criteria for Adverse Events, Version 3.0, based on this general guideline: Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE.
Time Frame Approximately 8 weeks (4 treatment cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set, defined as all participants in the Primary Analysis Set who received at least one dose of investigational product (IP; placebo or pegfilgrastim). One participant was randomized to the placebo arm but actually received pegfilgrastim and is included in the pegfilgrastim arm for the safety analyses.
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description:
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
Overall Number of Participants Analyzed 421 420
Measure Type: Number
Unit of Measure: participants
Any adverse event 355 344
Worst Grade of > 2 254 240
Worst Grade of > 3 119 115
Worst Grade of > 4 45 31
Serious adverse events 55 68
Severe adverse events 103 106
Life-threatening adverse events 43 27
Fatal adverse events 11 10
Leading to discontinuation of IP 1 3
Leading to discontinuation from study treatment 9 8
Time Frame Approximately 8 weeks (4 treatment cycles)
Adverse Event Reporting Description All participants in the Primary Analysis Set who received at least 1 dose of investigational product were included in the safety analysis set. One participant was randomized to the placebo arm but actually received pegfilgrastim and is included in the pegfilgrastim arm for the safety analyses.
 
Arm/Group Title Placebo Pegfilgrastim
Hide Arm/Group Description Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2, plus bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus placebo subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4). Participants received standard chemotherapy (FOLFOX or FOLFIRI) on Days 1-2 and bevacizumab 5 mg/kg intravenous (IV) infusion on Day 1 of each 14-day cycle plus pegfilgrastim 6 mg administered as a single subcutaneous injection once per cycle, for a maximum of 4 cycles, 24 hours after chemotherapy (Day 4).
All-Cause Mortality
Placebo Pegfilgrastim
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Pegfilgrastim
Affected / at Risk (%) Affected / at Risk (%)
Total   56/421 (13.30%)   68/420 (16.19%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  1/421 (0.24%)  0/420 (0.00%) 
Anaemia  1  1/421 (0.24%)  1/420 (0.24%) 
Coagulopathy  1  1/421 (0.24%)  0/420 (0.00%) 
Febrile neutropenia  1  1/421 (0.24%)  2/420 (0.48%) 
Granulocytopenia  1  0/421 (0.00%)  1/420 (0.24%) 
Leukocytosis  1  0/421 (0.00%)  1/420 (0.24%) 
Leukopenia  1  1/421 (0.24%)  1/420 (0.24%) 
Neutropenia  1  4/421 (0.95%)  3/420 (0.71%) 
Thrombocytopenia  1  0/421 (0.00%)  1/420 (0.24%) 
Cardiac disorders     
Atrial fibrillation  1  0/421 (0.00%)  1/420 (0.24%) 
Cardiac arrest  1  1/421 (0.24%)  2/420 (0.48%) 
Cardio-respiratory arrest  1  0/421 (0.00%)  1/420 (0.24%) 
Coronary artery disease  1  1/421 (0.24%)  0/420 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  3/421 (0.71%)  5/420 (1.19%) 
Ascites  1  0/421 (0.00%)  1/420 (0.24%) 
Colitis  1  0/421 (0.00%)  3/420 (0.71%) 
Colonic obstruction  1  0/421 (0.00%)  1/420 (0.24%) 
Colonic stenosis  1  1/421 (0.24%)  0/420 (0.00%) 
Constipation  1  1/421 (0.24%)  2/420 (0.48%) 
Diarrhoea  1  5/421 (1.19%)  10/420 (2.38%) 
Duodenal ulcer  1  1/421 (0.24%)  0/420 (0.00%) 
Enteritis  1  0/421 (0.00%)  1/420 (0.24%) 
Gastrointestinal haemorrhage  1  1/421 (0.24%)  0/420 (0.00%) 
Gastrointestinal inflammation  1  1/421 (0.24%)  0/420 (0.00%) 
Gastrointestinal perforation  1  0/421 (0.00%)  1/420 (0.24%) 
Haemorrhoidal haemorrhage  1  0/421 (0.00%)  1/420 (0.24%) 
Ileus  1  0/421 (0.00%)  4/420 (0.95%) 
Ileus paralytic  1  0/421 (0.00%)  1/420 (0.24%) 
Intestinal fistula  1  1/421 (0.24%)  0/420 (0.00%) 
Intestinal obstruction  1  2/421 (0.48%)  3/420 (0.71%) 
Intestinal perforation  1  1/421 (0.24%)  0/420 (0.00%) 
Large intestine perforation  1  2/421 (0.48%)  2/420 (0.48%) 
Nausea  1  1/421 (0.24%)  3/420 (0.71%) 
Neutropenic colitis  1  0/421 (0.00%)  1/420 (0.24%) 
Oral pain  1  1/421 (0.24%)  0/420 (0.00%) 
Rectal haemorrhage  1  3/421 (0.71%)  2/420 (0.48%) 
Rectal perforation  1  0/421 (0.00%)  1/420 (0.24%) 
Small intestinal obstruction  1  1/421 (0.24%)  1/420 (0.24%) 
Subileus  1  1/421 (0.24%)  1/420 (0.24%) 
Vomiting  1  3/421 (0.71%)  4/420 (0.95%) 
General disorders     
Asthenia  1  1/421 (0.24%)  1/420 (0.24%) 
Chest pain  1  1/421 (0.24%)  1/420 (0.24%) 
Fatigue  1  2/421 (0.48%)  0/420 (0.00%) 
General physical health deterioration  1  2/421 (0.48%)  0/420 (0.00%) 
Hernia  1  0/421 (0.00%)  1/420 (0.24%) 
Local swelling  1  0/421 (0.00%)  1/420 (0.24%) 
Medical device complication  1  1/421 (0.24%)  0/420 (0.00%) 
Mucosal inflammation  1  1/421 (0.24%)  0/420 (0.00%) 
Oedema peripheral  1  0/421 (0.00%)  1/420 (0.24%) 
Pyrexia  1  4/421 (0.95%)  5/420 (1.19%) 
Sudden death  1  1/421 (0.24%)  1/420 (0.24%) 
Hepatobiliary disorders     
Cholecystitis  1  0/421 (0.00%)  2/420 (0.48%) 
Cholecystitis acute  1  0/421 (0.00%)  1/420 (0.24%) 
Hepatorenal failure  1  1/421 (0.24%)  1/420 (0.24%) 
Hyperbilirubinaemia  1  1/421 (0.24%)  0/420 (0.00%) 
Immune system disorders     
Anaphylactic shock  1  0/421 (0.00%)  1/420 (0.24%) 
Infections and infestations     
Abscess rupture  1  0/421 (0.00%)  1/420 (0.24%) 
Bacterial sepsis  1  1/421 (0.24%)  0/420 (0.00%) 
Bronchopneumonia  1  0/421 (0.00%)  1/420 (0.24%) 
Candidiasis  1  0/421 (0.00%)  1/420 (0.24%) 
Clostridial infection  1  1/421 (0.24%)  0/420 (0.00%) 
Cystitis  1  2/421 (0.48%)  0/420 (0.00%) 
Device related infection  1  1/421 (0.24%)  1/420 (0.24%) 
Device related sepsis  1  0/421 (0.00%)  1/420 (0.24%) 
Helicobacter gastritis  1  1/421 (0.24%)  0/420 (0.00%) 
Herpes zoster  1  1/421 (0.24%)  0/420 (0.00%) 
Infection  1  2/421 (0.48%)  1/420 (0.24%) 
Kidney infection  1  1/421 (0.24%)  0/420 (0.00%) 
Neutropenic sepsis  1  1/421 (0.24%)  0/420 (0.00%) 
Oral candidiasis  1  1/421 (0.24%)  0/420 (0.00%) 
Oral fungal infection  1  1/421 (0.24%)  0/420 (0.00%) 
Pelvic infection  1  1/421 (0.24%)  0/420 (0.00%) 
Perirectal abscess  1  0/421 (0.00%)  1/420 (0.24%) 
Peritonitis  1  0/421 (0.00%)  2/420 (0.48%) 
Pneumonia  1  0/421 (0.00%)  1/420 (0.24%) 
Postoperative abscess  1  0/421 (0.00%)  1/420 (0.24%) 
Sepsis  1  1/421 (0.24%)  4/420 (0.95%) 
Soft tissue infection  1  0/421 (0.00%)  1/420 (0.24%) 
Urinary tract infection  1  2/421 (0.48%)  1/420 (0.24%) 
Injury, poisoning and procedural complications     
Hip fracture  1  1/421 (0.24%)  0/420 (0.00%) 
Infusion related reaction  1  1/421 (0.24%)  0/420 (0.00%) 
Rib fracture  1  0/421 (0.00%)  1/420 (0.24%) 
Investigations     
Electrocardiogram abnormal  1  1/421 (0.24%)  0/420 (0.00%) 
Neutrophil count decreased  1  1/421 (0.24%)  0/420 (0.00%) 
White blood cell count decreased  1  1/421 (0.24%)  0/420 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  2/421 (0.48%)  2/420 (0.48%) 
Dehydration  1  3/421 (0.71%)  5/420 (1.19%) 
Hypokalaemia  1  1/421 (0.24%)  4/420 (0.95%) 
Metabolic acidosis  1  0/421 (0.00%)  1/420 (0.24%) 
Tumour lysis syndrome  1  0/421 (0.00%)  1/420 (0.24%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  0/421 (0.00%)  1/420 (0.24%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour necrosis  1  0/421 (0.00%)  1/420 (0.24%) 
Nervous system disorders     
Cerebral infarction  1  1/421 (0.24%)  0/420 (0.00%) 
Cerebrovascular accident  1  1/421 (0.24%)  0/420 (0.00%) 
Lethargy  1  1/421 (0.24%)  0/420 (0.00%) 
Syncope  1  0/421 (0.00%)  1/420 (0.24%) 
Psychiatric disorders     
Anxiety  1  2/421 (0.48%)  1/420 (0.24%) 
Delirium  1  0/421 (0.00%)  1/420 (0.24%) 
Mental status changes  1  0/421 (0.00%)  1/420 (0.24%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/421 (0.24%)  0/420 (0.00%) 
Epistaxis  1  1/421 (0.24%)  0/420 (0.00%) 
Hiccups  1  0/421 (0.00%)  1/420 (0.24%) 
Lung disorder  1  0/421 (0.00%)  1/420 (0.24%) 
Pneumothorax  1  1/421 (0.24%)  0/420 (0.00%) 
Pulmonary embolism  1  3/421 (0.71%)  2/420 (0.48%) 
Rales  1  0/421 (0.00%)  1/420 (0.24%) 
Respiratory failure  1  1/421 (0.24%)  0/420 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  3/421 (0.71%)  2/420 (0.48%) 
Embolism venous  1  0/421 (0.00%)  1/420 (0.24%) 
Hypertension  1  1/421 (0.24%)  1/420 (0.24%) 
Hypertensive crisis  1  1/421 (0.24%)  0/420 (0.00%) 
Hypotension  1  1/421 (0.24%)  0/420 (0.00%) 
Orthostatic hypotension  1  1/421 (0.24%)  0/420 (0.00%) 
Phlebitis deep  1  1/421 (0.24%)  0/420 (0.00%) 
Subclavian vein thrombosis  1  1/421 (0.24%)  0/420 (0.00%) 
Thrombophlebitis  1  1/421 (0.24%)  0/420 (0.00%) 
Thrombosis  1  1/421 (0.24%)  0/420 (0.00%) 
Vena cava thrombosis  1  1/421 (0.24%)  0/420 (0.00%) 
Venous thrombosis  1  0/421 (0.00%)  3/420 (0.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Pegfilgrastim
Affected / at Risk (%) Affected / at Risk (%)
Total   310/421 (73.63%)   298/420 (70.95%) 
Blood and lymphatic system disorders     
Anaemia  1  23/421 (5.46%)  34/420 (8.10%) 
Neutropenia  1  121/421 (28.74%)  46/420 (10.95%) 
Gastrointestinal disorders     
Abdominal pain  1  21/421 (4.99%)  25/420 (5.95%) 
Constipation  1  47/421 (11.16%)  44/420 (10.48%) 
Diarrhoea  1  103/421 (24.47%)  107/420 (25.48%) 
Nausea  1  91/421 (21.62%)  115/420 (27.38%) 
Stomatitis  1  24/421 (5.70%)  9/420 (2.14%) 
Vomiting  1  45/421 (10.69%)  47/420 (11.19%) 
General disorders     
Asthenia  1  34/421 (8.08%)  31/420 (7.38%) 
Fatigue  1  64/421 (15.20%)  70/420 (16.67%) 
Pyrexia  1  31/421 (7.36%)  56/420 (13.33%) 
Investigations     
Weight decreased  1  19/421 (4.51%)  26/420 (6.19%) 
Metabolism and nutrition disorders     
Decreased appetite  1  31/421 (7.36%)  40/420 (9.52%) 
Hypokalaemia  1  15/421 (3.56%)  32/420 (7.62%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  14/421 (3.33%)  23/420 (5.48%) 
Nervous system disorders     
Neuropathy peripheral  1  25/421 (5.94%)  29/420 (6.90%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  23/421 (5.46%)  30/420 (7.14%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  17/421 (4.04%)  25/420 (5.95%) 
Vascular disorders     
Hypertension  1  28/421 (6.65%)  33/420 (7.86%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. 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 multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00911170     History of Changes
Other Study ID Numbers: 20080259
First Submitted: May 21, 2009
First Posted: June 1, 2009
Results First Submitted: November 19, 2013
Results First Posted: January 7, 2014
Last Update Posted: December 29, 2017