Cetuximab, Capecitabine, Oxaliplatin and Bevacizumab in Advanced Colorectal Cancer
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ClinicalTrials.gov Identifier: NCT00208546 |
Recruitment Status :
Completed
First Posted : September 21, 2005
Last Update Posted : February 2, 2012
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Tracking Information | ||||
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First Submitted Date ICMJE | September 13, 2005 | |||
First Posted Date ICMJE | September 21, 2005 | |||
Last Update Posted Date | February 2, 2012 | |||
Study Start Date ICMJE | June 2005 | |||
Actual Primary Completion Date | July 2009 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Cetuximab, Capecitabine, Oxaliplatin and Bevacizumab in Advanced Colorectal Cancer | |||
Official Title ICMJE | Cetuximab Added to Capecitabine, Oxaliplatin and Bevacizumab in Patients With Previously Untreated Advanced Colorectal Carcinoma, a Randomised Phase III Study | |||
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. |
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Detailed Description | Primary objective: To assess the efficacy, defined as progression-free survival (PFS), of adding cetuximab to capecitabine/oxaliplatin/bevacizumab 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 mg/m2 b.i.d. as of cycle 7. Arm A: capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (1250 mg/m2 after 6 cycles), oxaliplatin 130 mg/m2 i.v. infusion on day 1 during 6 cycles, bevacizumab 7.5 mg/kg i.v. infusion on day 1. Arm B: capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (1250 mg/m2 after 6 cycles), oxaliplatin 130 mg/m2 i.v. infusion on day 1 during 6 cycles, bevacizumab 7.5 mg/kg i.v. infusion on day 1. Cetuximab 400 mg/m2 i.v. day 1 of cycle 1, thereafter weekly 250 mg/m2 i.v. 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 and/or progression should be reported whenever it occurs. In case chemotherapy (i.e. capecitabine and/or 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 (i.e. 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 toxicity/symptomatology will be graded according to NCI common toxicity criteria, version 3.0. 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 (>=0.05, 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:
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. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 3 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Colorectal Cancer | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
750 | |||
Original Enrollment ICMJE | Same as current | |||
Actual Study Completion Date ICMJE | December 2009 | |||
Actual Primary Completion Date | July 2009 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria: Histology and Staging Disease
General Conditions
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Netherlands | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT00208546 | |||
Other Study ID Numbers ICMJE | CAIRO2 | |||
Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Dutch Colorectal Cancer Group | |||
Original Responsible Party | Not Provided | |||
Current Study Sponsor ICMJE | Dutch Colorectal Cancer Group | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Dutch Colorectal Cancer Group | |||
Verification Date | February 2012 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |