A Study of Radiotherapy in Rectal Cancer Using Oxaliplatin, Capecitabine With or Without Cetuximab
Recruitment status was Recruiting
|First Received Date ICMJE||November 20, 2008|
|Last Updated Date||November 20, 2008|
|Start Date ICMJE||July 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||A Study of Radiotherapy in Rectal Cancer Using Oxaliplatin, Capecitabine With or Without Cetuximab|
|Official Title ICMJE||A Randomized, Phase II Study of Concurrent Radiotherapy and Oxaliplatin, Capecitabine With or Without Cetuximab in Rectal Cancer Tumor Stratified by KRAS Mutation Status.|
Primary Objectives To estimate the pathological complete response rate following neoadjuvant radiotherapy with concurrent capecitabine and oxaliplatin, with or without cetuximab based on the KRAS mutation status in rectal cancer.
Aims: The primary aim of this study is to estimate the pathological complete response rate following neoadjuvant radiotherapy with concurrent capecitabine and oxaliplatin (CAPOX), with or without cetuximab based on the KRAS mutation status in rectal cancer.
Hypothesis: Cetuximab, a monoclonal antibody targeted against the EGF receptor, is active in metastatic colorectal cancer and a radio-sensitizer. In colorectal cancer, the presence of KRAS mutation has been associated with the absence of response to cetuximab. We hypothesise that the addition of cetuximab to CAPOX concurrent with neoadjuvant radiotherapy only benefited patients whose tumours do not have the KRAS mutation and therefore, personalizing cetuximab therapy based on tumour KRAS mutation status may yield a higher pathological response.
Methods: This study employed a standard 2-stage Phase II design to evaluate the efficacy and tolerability of two neoadjuvant chemoradiotherapy regimens. The assignment of the neoadjuvant chemotherapy will be determined by the KRAS mutation status of the tumor. Subjects with KRAS mutation will receive CAPOX. Subjects with no KRAS mutation will be randomized to receive CAPOX +/- cetuximab.Definitive surgery is scheduled for 6-8 weeks after the completion of chemoradiotherapy. Surgical management will be a sphincter preservation approach whenever possible, using the total mesorectal excision technique.After the operation, pathologic evaluation of the surgical specimen will be performed.
Significance:In this proof-of-concept study, we aim to demonstrate that using an enriched patient cohort to test our hypothesis that the addition of cetuximab will yield a higher pathological response rate in KRAS mutation-negative rectal cancer. This approach can potentially identify a subset of patients that may benefit from cetuximab and spare those who may not benefit from unnecessary treatment toxicities and costs. Our study will help to prioritise novel targeted agents for a smaller, faster, and less expensive confirmatory phase III trials.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
|Condition ICMJE||Rectal Cancer|
|Intervention ICMJE||Drug: Capecitabine, Cetuximab, Oxaliplatin|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||21 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||Singapore|
|NCT Number ICMJE||NCT00795301|
|Other Study ID Numbers ICMJE||CR02/06/07|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Wei Peng Yong, National University Hospital|
|Study Sponsor ICMJE||National University Hospital, Singapore|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National University Hospital, Singapore|
|Verification Date||November 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP