Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00208546
Status:
COMPLETED
Last Update Posted:
2012-02-02
First Post:
2005-09-13
Brief Title:
Cetuximab Capecitabine Oxaliplatin and Bevacizumab in Advanced Colorectal Cancer
Sponsor:
Dutch Colorectal Cancer Group
Organization:
Dutch Colorectal Cancer Group
Study Overview
Official Title:
Cetuximab Added to Capecitabine Oxaliplatin and Bevacizumab in Patients With Previously Untreated Advanced Colorectal Carcinoma a Randomised Phase III Study
Status:
COMPLETED
Status Verified Date:
2012-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a study to assess the efficacy and safety of the addition of cetuximab to the combined regimen of capecitabine oxaliplatin and bevacizumab in patients with previously untreated advanced colorectal carcinoma It is an open comparative study comparing the effects of capecitabine oxaliplatin and bevacizumab to those of the same regimen plus cetuximab
Seven hundred fifty patients will be included Treatment will continue until disease progression or serious toxicity and follow up will continue until death It is anticipated that the addition of cetuximab will lead to an increase in progression free survival
Seven hundred fifty patients will be included Treatment will continue until disease progression or serious toxicity and follow up will continue until death It is anticipated that the addition of cetuximab will lead to an increase in progression free survival
Detailed Description:
Primary objective To assess the efficacy defined as progression-free survival PFS of adding cetuximab to capecitabineoxaliplatinbevacizumab for advanced CRC
Secondary objectives To assess tumour response CR PR or SD response duration overall survival toxicity profile quality of life translational research
Methodology Open randomised multicenter phase III study The number of patients is 750
Test products All cycles will be administered q 3 weeks Oxaliplatin will be discontinued after 6 cycles in both study arms The dose of capecitabine will be increased to 1250 mgm2 bid as of cycle 7
Arm A capecitabine 1000 mgm2 orally bid on day 1-14 1250 mgm2 after 6 cycles oxaliplatin 130 mgm2 iv infusion on day 1 during 6 cycles bevacizumab 75 mgkg iv infusion on day 1
Arm B capecitabine 1000 mgm2 orally bid on day 1-14 1250 mgm2 after 6 cycles oxaliplatin 130 mgm2 iv infusion on day 1 during 6 cycles bevacizumab 75 mgkg iv infusion on day 1 Cetuximab 400 mgm2 iv day 1 of cycle 1 thereafter weekly 250 mgm2 iv
Duration of treatment and follow-up Treatment is continued until disease progression or unacceptable toxicity Patients will be evaluated every 9 weeks for response while on treatment or at any other time point when progression is suspected After cessation of therapy for reasons other than disease progression patients will be followed every 3 months until progression or death Death andor progression should be reported whenever it occurs
In case chemotherapy ie capecitabine andor oxaliplatin is discontinued for reasons of toxicity treatment with bevacizumab arm A or bevacizumab cetuximab Arm B should be continued until progression or unacceptable toxicity Also if chemotherapy plus bevacizumab is discontinued in Arm B for reasons of toxicity treatment with cetuximab should be continued until progression or unacceptable toxicity
Criteria for evaluation
Efficacy All eligible patients will be included in the analysis intent-to-treat All patients receiving 9 weeks of treatment ie 3 cycles will be considered evaluable for response unless documented progression occurred earlier
Safety profile Safety will be analysed in each treatment group Patients having received 1 treatment doses are evaluable for toxicity Evaluation will be performed on the safety population having received treatment assignment to treatment groups as treated Clinical and laboratory toxicitysymptomatology will be graded according to NCI common toxicity criteria version 30 The adverse events which are not reported in NCI common toxicity criteria will be graded as mild moderate severe life threatening
Statistical methodology The main endpoint of the study is the progression free survival interval PFS PFS curves will be constructed by means of the Kaplan Meier method Comparisons of PFS curves will performed by mean of the log rank test Similar methods will be used to analyse the duration of survival All analyses will be done according to the intention-to-treat principle
The expected median PFS in Arm A standard arm is 11 months The minimum increase in PFS in Arm B experimental arm will be 3 months 21 hazard ratio reduction 540 events are required for 80 power 740 patients are needed to show this difference 005 2-tailed test To allow for ineligibility in some patients a total of 750 patients will be included
Stratification parameters
Patients will be stratified for the following parameters
Prior adjuvant therapy yes versus no
Number of organs affected 1 versus 1 in case the primary tumour is in situ this will count as one organ
Serum LDH normal versus above normal
Per participating institution
Side studies Side studies on prognostic factors in tumour samples from included patients will be performed as well as on circulating tumour cells and endothelial cells and serum proteomics
Secondary objectives To assess tumour response CR PR or SD response duration overall survival toxicity profile quality of life translational research
Methodology Open randomised multicenter phase III study The number of patients is 750
Test products All cycles will be administered q 3 weeks Oxaliplatin will be discontinued after 6 cycles in both study arms The dose of capecitabine will be increased to 1250 mgm2 bid as of cycle 7
Arm A capecitabine 1000 mgm2 orally bid on day 1-14 1250 mgm2 after 6 cycles oxaliplatin 130 mgm2 iv infusion on day 1 during 6 cycles bevacizumab 75 mgkg iv infusion on day 1
Arm B capecitabine 1000 mgm2 orally bid on day 1-14 1250 mgm2 after 6 cycles oxaliplatin 130 mgm2 iv infusion on day 1 during 6 cycles bevacizumab 75 mgkg iv infusion on day 1 Cetuximab 400 mgm2 iv day 1 of cycle 1 thereafter weekly 250 mgm2 iv
Duration of treatment and follow-up Treatment is continued until disease progression or unacceptable toxicity Patients will be evaluated every 9 weeks for response while on treatment or at any other time point when progression is suspected After cessation of therapy for reasons other than disease progression patients will be followed every 3 months until progression or death Death andor progression should be reported whenever it occurs
In case chemotherapy ie capecitabine andor oxaliplatin is discontinued for reasons of toxicity treatment with bevacizumab arm A or bevacizumab cetuximab Arm B should be continued until progression or unacceptable toxicity Also if chemotherapy plus bevacizumab is discontinued in Arm B for reasons of toxicity treatment with cetuximab should be continued until progression or unacceptable toxicity
Criteria for evaluation
Efficacy All eligible patients will be included in the analysis intent-to-treat All patients receiving 9 weeks of treatment ie 3 cycles will be considered evaluable for response unless documented progression occurred earlier
Safety profile Safety will be analysed in each treatment group Patients having received 1 treatment doses are evaluable for toxicity Evaluation will be performed on the safety population having received treatment assignment to treatment groups as treated Clinical and laboratory toxicitysymptomatology will be graded according to NCI common toxicity criteria version 30 The adverse events which are not reported in NCI common toxicity criteria will be graded as mild moderate severe life threatening
Statistical methodology The main endpoint of the study is the progression free survival interval PFS PFS curves will be constructed by means of the Kaplan Meier method Comparisons of PFS curves will performed by mean of the log rank test Similar methods will be used to analyse the duration of survival All analyses will be done according to the intention-to-treat principle
The expected median PFS in Arm A standard arm is 11 months The minimum increase in PFS in Arm B experimental arm will be 3 months 21 hazard ratio reduction 540 events are required for 80 power 740 patients are needed to show this difference 005 2-tailed test To allow for ineligibility in some patients a total of 750 patients will be included
Stratification parameters
Patients will be stratified for the following parameters
Prior adjuvant therapy yes versus no
Number of organs affected 1 versus 1 in case the primary tumour is in situ this will count as one organ
Serum LDH normal versus above normal
Per participating institution
Side studies Side studies on prognostic factors in tumour samples from included patients will be performed as well as on circulating tumour cells and endothelial cells and serum proteomics
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None