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Trial record 54 of 318 for:    colon cancer | ( Map: Canada )

A Study of Xeloda (Capecitabine) in Combination With Oxaliplatin in Patients With Metastatic Colorectal Cancer.

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ClinicalTrials.gov Identifier: NCT00353262
Recruitment Status : Completed
First Posted : July 18, 2006
Results First Posted : January 8, 2016
Last Update Posted : March 4, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: Avastin
Drug: Oxaliplatin
Drug: capecitabine [Xeloda]
Enrollment 36
Recruitment Details A total of 36 participants were enrolled in this study at three sites in Canada between 8 August 2005 and 24 April 2008.
Pre-assignment Details  
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Period Title: Overall Study
Started 36
Completed 7
Not Completed 29
Reason Not Completed
Adverse Event             8
Withdrawal by Subject             2
Insufficient Therapeutic Response             13
Progression             1
Surgery             4
Break from Chemotherapy             1
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Baseline Participants 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants
57.3  (13.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants
Female
21
  58.3%
Male
15
  41.7%
1.Primary Outcome
Title Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0–Inf) of 5’-Deoxy-5-fluorouridine 5’-(DFUR)
Hide Description AUC0-infinity represents the area under the concentration-time curve of the analyte (5’-DFUR) in plasma over the time interval from 0 extrapolated to infinity. The analyte 5’-DFUR, the direct precursor of 5-fluorouracil (5-FU), is considered to be the most important metabolite of capecitabine in plasma. The unit of measure was nanograms per millilitre per hour (ng/mL * hr).
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*hr
Cycle 1, Day 1
13605
(33%)
Cycle 2, Day 1
12177
(27%)
Cycle 3, Day 1
11817
(38%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.90
Confidence Interval (2-Sided) 90%
0.79 to 1.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 90%
0.76 to 0.99
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Cycle 3, Day 1 to Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 90%
0.85 to 1.10
Estimation Comments [Not Specified]
2.Primary Outcome
Title AUC0-inf for Free Platinum
Hide Description AUC0-infinity represents the area under the concentration-time curve of the analyte (free platinum) in plasma over the time interval from 0 extrapolated to infinity. AUC0-inf for free platinum was calculated for each participant from the concentration-data obtained on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. Free platinum is not bound to plasma proteins and is considered to be the most clinically significant measure of pharmacological and toxicological activity.
Time Frame Predose , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the 2 hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL * hr
Cycle 1, Day 2
10069
(23%)
Cycle 2 , Day 1
10537
(24%)
Cycle 3, Day 1.
10225
(23%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Cycle 2, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 90%
1.01 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Cycle 3, Day 1 to Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 90%
0.98 to 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Cycle 3, Day 1 to Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 90%
0.94 to 1.00
Estimation Comments [Not Specified]
3.Secondary Outcome
Title AUC (0-infinity) of Capecitabine and Its Metabolites (5’-DFCR, 5-FU, and FBAL)
Hide Description AUC0-infinity represents the area under the concentration-time curve of the analytes (5’-DFCR, 5-FU, and FBAL) in plasma over the time interval from 0 extrapolated to infinity. After oral administration, capecitabine is first metabolized in the liver to 5’-deoxy-5-fluorocytidine (5’-DFCR), which is then converted to 5’-DFUR, and then catalytically activated to 5-FU.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*hr
Capcetabine , Cycle 1, Day 1
5217
(57%)
Capcetabine , Cycle 2, Day 1
5299
(54%)
Capcetabine , Cycle 3, Day 1
6130
(68%)
5’-DFCR , Cycle 1, Day 1
7630
(76%)
5’-DFCR , Cycle 2, Day 1
6409
(47%)
5’-DFCR, Cylce 3, Day 1
7989
(52%)
5-FU , Cycle 1, Day 1
437
(92%)
5-FU , Cycle 2, Day 1
355
(50%)
5-FU , Cycle 3, Day 1
343
(86%)
FBAL , Cycle 1, Day 1
17904
(27%)
FBAL , Cycle 2, Day 1
17413
(26%)
FBAL , Cycle 3, Day 1
17356
(34%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Capecitabine: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 90%
0.83 to 1.24
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Capecitabine: Cycle 3, Day 1 to Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.16
Confidence Interval (2-Sided) 90%
0.94 to 1.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Capecitabine: Cycle 3, Day 1 to Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.17
Confidence Interval (2-Sided) 90%
0.96 to 1.44
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFCR: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 90%
0.69 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFCR: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.08
Confidence Interval (2-Sided) 90%
0.86 to 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFCR: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.25
Confidence Interval (2-Sided) 90%
1.00 to 1.55
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5-FU: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 90%
0.66 to 1.01
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5-FU: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 90%
0.64 to 0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5-FU: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 90%
0.78 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments FBAL: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 90%
0.91 to 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments FBAL: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 90%
0.90 to 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments FBAL: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 90%
0.93 to 1.07
Estimation Comments [Not Specified]
4.Secondary Outcome
Title AUC0-last of Capecitabine and Its Metabolites (5’-DFUR, 5’-DFCR, 5 FU, and FBAL)
Hide Description Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of capecitabine and its metabolites (5’-DFUR, 5’-DFCR, 5 FU, and FBAL).
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL*hr
5’ DFUR , Cycle 1, Day 1
13503
(33%)
5’ DFUR, Cycle 2 , Day 1
12057
(28%)
5’ DFUR, Cycle 3, Day 1
11618
(38%)
Capecitabine, Cycle 1, Day 1
5201
(57%)
Capecitabine, Cycle 2, Day 1
5273
(54%)
Capecitabine, Cycle 3, Day 1
6093
(68%)
5’-DFCR, Cycle 1, Day 1
6150
(80%)
5’-DFCR, Cycle 2 , Day 1
6378
(47%)
5’-DFCR, Cycle 3, Day 1
7909
(52%)
5-FU, Cycle 1, Day 1
433
(92%)
5-FU, Cycle 2, Day 1
350
(51%)
5-FU, Cycle 3, Day 1
336
(84%)
FBAL, Cycle 1, Day 1
16773
(26%)
FBAL, Cycle 2, Day 1
15992
(26%)
FBAL, Cycle 3, Day 1
14947
(31%)
5.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5’-DFUR, 5’-DFCR, 5 FU, and FBAL)
Hide Description Cmax is defined as maximum observed analyte concentration of capecitabine and its metabolites (5’-DFUR, 5’-DFCR, 5 FU, and FBAL)
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
5’-DFUR, Cycle 1, Day 1
8847
(48%)
5’-DFUR , Cycle 2, Day 1
6545
(48%)
5’-DFUR , Cycle 3, Day 1
5693
(54%)
Capecitabine, Cycle 1, Day 1
4930
(72%)
Capecitabine, Cycle 2, Day 1
4065
(73%)
Capecitabine, Cycle 3, Day 1
4167
(81%)
5’ DFCR, Cycle 1, Day 1
3902
(78%)
5’ DFCR, Cycle 2, Day 1
3407
(66%)
5’ DFCR , Cycle 3, Day 1
3747
(69%)
5-FU, Cycle 1 , Day 1
292
(63%)
5-FU, Cycle 2, Day 1
216
(63%)
5-FU, Cycle 3, Day 1
168
(83%)
FBAL, Cycle 1, Day 1
3970
(19%)
FBAL, Cycle 2, Day 1
3627
(27%)
FBAL, Cycle 3, Day 1
3292
(34%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFUR: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.74
Confidence Interval (2-Sided) 90%
0.61 to 0.90
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFUR: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 90%
0.53 to 0.79
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFUR: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 90%
0.71 to 1.06
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Capecitabine: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 90%
0.63 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Capecitabine: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 90%
0.78 to 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Capecitabine: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 90%
0.65 to 1.10
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFCR: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 90%
0.65 to 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFCR: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.96
Confidence Interval (2-Sided) 90%
0.71 to 1.30
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5'-DFCR: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.10
Confidence Interval (2-Sided) 90%
0.81 to 1.49
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5-FU: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.74
Confidence Interval (2-Sided) 90%
0.56 to 0.98
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5-FU: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.58
Confidence Interval (2-Sided) 90%
0.44 to 0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments 5-FU: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.78
Confidence Interval (2-Sided) 90%
0.59 to 1.03
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments FBAL: Cycle 2, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.91
Confidence Interval (2-Sided) 90%
0.83 to 1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments FBAL: Cycle 3, Day 1 versus Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 90%
0.76 to 0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments FBAL: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.91
Confidence Interval (2-Sided) 90%
0.83 to 1.00
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5’-DFUR , 5’-DFCR, 5 FU, and FBAL)
Hide Description t1/2 Beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of capecitabine and its metabolites (5’-DFUR , 5’-DFCR, 5 FU, and FBAL)
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour
5’ DFUR; Cycle 1, Day 1
0.65
(19%)
5’ DFUR, Cycle 2 , Day 1
0.64
(49%)
5’ DFUR, Cycle 3, Day 1
0.75
(39%)
Capecitabine, Cycle 1, Day 1
0.37
(52%)
Capecitabine, Cycle 2, Day 1
0.51
(55%)
Capecitabine, Cycle 3, Day 1
0.56
(42%)
5’-DFCR, Cycle 1, Day 1
0.71
(33%)
5’-DFCR, Cycle 2 , Day 1
0.75
(32%)
5’-DFCR, Cycle 3, Day 1
0.79
(24%)
5-FU, Cycle 1, Day 1
0.61
(20%)
5-FU, Cycle 2, Day 1
0.67
(61%)
5-FU, Cycle 3, Day 1
0.71
(31%)
FBAL, Cycle 1, Day 1
2.77
(19%)
FBAL, Cycle 2, Day 1
2.68
(26%)
FBAL, Cycle 3, Day 1
2.64
(33%)
7.Secondary Outcome
Title AUC0-infinity for Total Platinum
Hide Description AUC0-infinity represents the area under the concentration-time curve of the analyte (total platinum) in plasma over the time interval from 0 extrapolated to infinity.
Time Frame Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL* hr
Cycle 1, Day 2
139329
(24%)
Cycle 2, Day 1
167610
(17%)
Cycle 3, Day 1
186268
(21%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Total Platinum: Cycle 2, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.20
Confidence Interval (2-Sided) 90%
1.09 to 1.33
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Total Platinum: Cycle 3, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.34
Confidence Interval (2-Sided) 90%
1.21 to 1.48
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Total Platinum: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.11
Confidence Interval (2-Sided) 90%
1.01 to 1.23
Estimation Comments [Not Specified]
8.Secondary Outcome
Title AUC0-last of Total And Free Platinum
Hide Description Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of Total And Free Platinum.
Time Frame pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL* hr
Total Platinum: Cycle 1, Day 2
85406
(20%)
Total Platinum: Cycle 2, Day 1
97083
(12%)
Total Platinum: Cycle 3, Day 1
97011
(17%)
Free Platinum: Cycle 1, Day 2
9399
(24%)
Free Platinum: Cycle 2, Day 1
9818
(25%)
Free Platinum: Cycle 3, Day 1
9604
(22%)
9.Secondary Outcome
Title Cmax of Total And Free Platinum
Hide Description Cmax is defined as maximum observed analyte concentration of Total And Free Platinum.
Time Frame Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Total Platinum: Cycle 1, Day 2
3652
(14%)
Total Platinum: Cycle 2, Day 1
3741
(19%)
Total Platinum: Cycle 3, Day 1
3706
(21%)
Free Platinum: Cycle 1, Day 2
1818
(27%)
Free Platinum: Cycle 2, Day 1
1840
(36%)
Free Platinum: Cycle 3, Day 1
1813
(30%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Total Platinum: Cycle 2, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 90%
0.96 to 1.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Total Platinum: Cycle 3, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.01
Confidence Interval (2-Sided) 90%
0.95 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Total Platinum: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 90%
0.93 to 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Free Platinum: Cycle 2, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.01
Confidence Interval (2-Sided) 90%
0.94 to 1.09
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Free Platinum: Cycle 3, Day 1 versus Cycle 1, Day 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 90%
0.92 to 1.08
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Capecitabine+ Oxaliplatin+ Bevacizumab
Comments Free Platinum: Cycle 3, Day 1 versus Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 90%
0.91 to 1.07
Estimation Comments [Not Specified]
10.Secondary Outcome
Title T1/2 Beta of Total And Free Platinum
Hide Description T1/2 beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of total and free platinum.
Time Frame Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour
Total Platinum: Cycle 1, Day 2
48.70
(30%)
Total Platinum: Cycle 2, Day 1
55.73
(24%)
Total Platinum: Cycle 3, Day 1
67.28
(26%)
Free Platinum: Cycle 1, Day 2
17.64
(10%)
Free Platinum: Cycle 2, Day 1
18.41
(9%)
Free Platinum: Cycle 3, Day 1
18.47
(10.90%)
11.Secondary Outcome
Title Volume of Distribution at Steady State (VSS) of Total And Free Platinum
Hide Description VSS is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time Frame Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL
Total Platinum: Cycle 1, Day 2
109007
(23%)
Total Platinum: Cycle 2, Day 1
105097
(21%)
Total Platinum: Cycle 3, Day 1
112141
(21%)
Free Platinum: Cycle 1, Day 2
387158
(23%)
Free Platinum: Cycle 2, Day 1
389193
(29%)
Free Platinum: Cycle 3, Day 1
401040
(24%)
12.Secondary Outcome
Title Clearance of Total And Free Platinum
Hide Description CL is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (hour).
Time Frame Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/Hr
Total Platinum: Cycle 1, Day 2
1603
(78%)
Total Platinum: Cycle 2, Day 1
1331
(22%)
Total Platinum: Cycle 3, Day 1
1198
(25%)
Free Platinum: Cycle 1, Day 2
22183
(23%)
Free Platinum: Cycle 2, Day 1
21176
(26%)
Free Platinum: Cycle 3, Day 1
21823
(23%)
13.Secondary Outcome
Title Number Of Participants With Adverse Events (AEs)
Hide Description An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. This includes any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during the study were also to be reported as AEs.
Time Frame Approximately 3 Years (up to 28 days after the last intake of study medication)
Hide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received at least one dose of capecitabine.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 36
Measure Type: Number
Unit of Measure: Participants
Any AE 36
Any SAE 16
14.Secondary Outcome
Title Marked Laboratory Abnormalities
Hide Description Number of participants with marked laboratory abnormalities (hematology, coagulation, liver function, renal function, protein, electrolytes, miscellaneous).
Time Frame Up to 28 days after last chemotherapy administration
Hide Outcome Measure Data
Hide Analysis Population Description
All 36 participants who received at least one dose of capecitabine.
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description:
In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
Overall Number of Participants Analyzed 36
Measure Type: Number
Unit of Measure: Participants
Hematocrit - high 2
Hematocrit - low 5
Hemoglobin - low 6
Platelets - high 1
Platelets - low 9
RBC - low 12
WBC - high 1
WBC - low 7
Neutrophils - high 1
Neutrophils - low 3
PT (INR) - high 2
ASAT (SGOT) - high 6
LDH - high 2
ALAT (SGPT) - high 7
Alk. Phos. - high 6
Dir. Bilirubin - high 3
Total Bilirubin - high 2
Creatinine - high 0
Albumin - low 4
Potassium - low 2
Sodium - low 2
Calcium - low 1
Glucose Fasting - high 4
Time Frame Approximately 3 Years (up to 28 days after the last intake of study medication)
Adverse Event Reporting Description Adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and includes any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
 
Arm/Group Title Capecitabine+ Oxaliplatin+ Bevacizumab
Hide Arm/Group Description In Cycle 1, participants received a single oral dose of capecitabine 1000 milligrams per meter square (mg/m^2 on Day 1 followed by 2-hour intravenous (IV) infusion of oxaliplatin 130 mg/m^2 on Day 2 followed by oral dosing of capecitabine 1000 mg/m^2 twice-daily (BID) from Day 5 to Day 14 . In Cycle 2, participants received IV infusion of oxaliplatin 130 mg//m^2 over 2 hours on Day 1 along with capecitabine 1000 mg/m^2 orally BID until Day 14. In Cycle 3, participants received IV infusion of bevacizumab 7.5 mg/kg over 90 minutes on Day 1 at the same time as oxaliplatin 130 mg//m^2 was administered as an IV infusion over 2 hours (Day 1 every 3 weeks) along with capecitabine1000 mg//m^2 orally BID until Day 14. Treatment with the Cycle 3 dosing regimen continued for a further 13 cycles (i.e. Cycle 16) or until progressive disease or unacceptable toxicity or until the participant withdrew consent
All-Cause Mortality
Capecitabine+ Oxaliplatin+ Bevacizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Capecitabine+ Oxaliplatin+ Bevacizumab
Affected / at Risk (%)
Total   16/36 (44.44%) 
Blood and lymphatic system disorders   
Neutropenia  1  2/36 (5.56%) 
Thrombocytopenia  1  1/36 (2.78%) 
Gastrointestinal disorders   
Diarrhoea  1  4/36 (11.11%) 
Abdominal pain  1  2/36 (5.56%) 
Gastrointestinal haemorrhage  1  2/36 (5.56%) 
Enteritis  1  1/36 (2.78%) 
Intestinal obstruction  1  1/36 (2.78%) 
Vomiting  1  1/36 (2.78%) 
General disorders   
Pyrexia  1  3/36 (8.33%) 
Pain  1  1/36 (2.78%) 
Injury, poisoning and procedural complications   
Hip fracture  1  1/36 (2.78%) 
Metabolism and nutrition disorders   
Dehydration  1  6/36 (16.67%) 
Psychiatric disorders   
Anxiety  1  1/36 (2.78%) 
Depression  1  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism  1  1/36 (2.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Capecitabine+ Oxaliplatin+ Bevacizumab
Affected / at Risk (%)
Total   36/36 (100.00%) 
Blood and lymphatic system disorders   
Neutropenia  1  11/36 (30.56%) 
Anaemia  1  3/36 (8.33%) 
Thrombocytopenia  1  2/36 (5.56%) 
Cardiac disorders   
Palpitations  1  2/36 (5.56%) 
Tachycardia  1  2/36 (5.56%) 
Eye disorders   
Lacrimation increased  1  6/36 (16.67%) 
Vision blurred  1  3/36 (8.33%) 
Gastrointestinal disorders   
Nausea  1  30/36 (83.33%) 
Diarrhoea  1  29/36 (80.56%) 
Vomiting  1  21/36 (58.33%) 
Abdominal pain  1  14/36 (38.89%) 
Constipation  1  10/36 (27.78%) 
Abdominal discomfort  1  7/36 (19.44%) 
Flatulence  1  6/36 (16.67%) 
Dyspepsia  1  5/36 (13.89%) 
Rectal haemorrhage  1  4/36 (11.11%) 
Stomatitis  1  4/36 (11.11%) 
Abdominal pain upper  1  3/36 (8.33%) 
Haematochezia  1  3/36 (8.33%) 
Toothache  1  3/36 (8.33%) 
Anorectal discomfort  1  2/36 (5.56%) 
Dry mouth  1  2/36 (5.56%) 
Dysphagia  1  2/36 (5.56%) 
Gastrooesophageal reflux Disease  1  2/36 (5.56%) 
Haemorrhoids  1  2/36 (5.56%) 
Rectal Discharge  1  2/36 (5.56%) 
General disorders   
Fatigue  1  32/36 (88.89%) 
Temperature intolerance  1  10/36 (27.78%) 
Mucosal inflammation  1  9/36 (25.00%) 
Oedema peripheral  1  7/36 (19.44%) 
Pyrexia  1  4/36 (11.11%) 
Catheter site erythema  1  3/36 (8.33%) 
Chills  1  3/36 (8.33%) 
Injection site pain  1  3/36 (8.33%) 
Pain  1  3/36 (8.33%) 
Catheter related complication  1  2/36 (5.56%) 
Catheter site rash  1  2/36 (5.56%) 
Chest discomfort  1  2/36 (5.56%) 
Injection site discolouration  1  2/36 (5.56%) 
Immune system disorders   
Hypersensitivity  1  2/36 (5.56%) 
Investigations   
Gamma−glutamyltransferase increased  1  2/36 (5.56%) 
Weight decreased  1  2/36 (5.56%) 
Metabolism and nutrition disorders   
Anorexia  1  20/36 (55.56%) 
Hypokalaemia  1  10/36 (27.78%) 
Dehydration  1  7/36 (19.44%) 
Hyponatraemia  1  3/36 (8.33%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  9/36 (25.00%) 
Muscle spasms  1  6/36 (16.67%) 
Muscular weakness  1  6/36 (16.67%) 
Arthralgia  1  4/36 (11.11%) 
Joint stiffness  1  4/36 (11.11%) 
Back pain  1  3/36 (8.33%) 
Pain in jaw  1  3/36 (8.33%) 
Musculoskeletal pain  1  2/36 (5.56%) 
Myalgia  1  2/36 (5.56%) 
Trismus  1  2/36 (5.56%) 
Nervous system disorders   
Peripheral sensory neuropathy  1  22/36 (61.11%) 
Neuropathy peripheral  1  14/36 (38.89%) 
Headache  1  9/36 (25.00%) 
Paraesthesia  1  6/36 (16.67%) 
Dysgeusia  1  5/36 (13.89%) 
Dizziness  1  4/36 (11.11%) 
Ataxia  1  2/36 (5.56%) 
Neuralgia  1  2/36 (5.56%) 
Psychiatric disorders   
Anxiety  1  7/36 (19.44%) 
Insomnia  1  7/36 (19.44%) 
Confusional state  1  4/36 (11.11%) 
Depression  1  3/36 (8.33%) 
Restlessness  1  2/36 (5.56%) 
Renal and urinary disorders   
Dysuria  1  2/36 (5.56%) 
Proteinuria  1  2/36 (5.56%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  7/36 (19.44%) 
Cough  1  6/36 (16.67%) 
Pharyngolaryngeal pain  1  5/36 (13.89%) 
Dysphonia  1  4/36 (11.11%) 
Dyspnoea  1  4/36 (11.11%) 
Dyspnoea exertional  1  4/36 (11.11%) 
Hiccups  1  2/36 (5.56%) 
Rhinorrhoea  1  2/36 (5.56%) 
Wheezing  1  2/36 (5.56%) 
Skin and subcutaneous tissue disorders   
Palmar−plantar  1  20/36 (55.56%) 
Erythrodysaesthesia syndrome Dry skin  1  5/36 (13.89%) 
Rash  1  5/36 (13.89%) 
Skin hyperpigmentation  1  5/36 (13.89%) 
Nail disorder  1  3/36 (8.33%) 
Dermatitis acneiform  1  2/36 (5.56%) 
Hyperhidrosis  1  2/36 (5.56%) 
Vascular disorders   
Thrombosis  1  6/36 (16.67%) 
Hypertension  1  5/36 (13.89%) 
Flushing  1  3/36 (8.33%) 
Hypotension  1  3/36 (8.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 616878333
EMail: global.trial_information@roche.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00353262     History of Changes
Other Study ID Numbers: NP18587
First Submitted: July 17, 2006
First Posted: July 18, 2006
Results First Submitted: December 4, 2015
Results First Posted: January 8, 2016
Last Update Posted: March 4, 2016