Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00173472
Status:
UNKNOWN
Last Update Posted:
2005-11-24
First Post:
2005-09-12
Brief Title:
Association of MSI TS DPD MVD and EGFR With Chemosensitivity in Stage IV in Colorectal Cancer
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Association of MSI TS DPD MVD and EGFR With Chemosensitivity in Stage IV in Colorectal Cancer
Status:
UNKNOWN
Status Verified Date:
2002-07
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
The present project will follow our previous phaseⅡ study of FOLFOX regimens for the treatment of stage Ⅳ colorectal cancer We will recruit at least 200 patients for this study The selection of patients will be based on rigorous eligibility criteria The patients will be allocated based on the expression of each molecular marker MSI TS DPD MVD and EGFR and the implementation of chemotherapy For example in the examination for the clinical implications of EGFR the patients will be classified into four groups EGFR chemotherapy EGFR chemotherapy- EGFR- chemotherapy EGFR- chemotherapy- Base on the analysis of this 22 table we will clarify the prognostic significance of a specific molecular marker is due to whether the specific molecular marker predicts biological invasiveness andor chemosensitivity We believe the present study will have the following significance 1To further clarify the mechanisms for the carcinogenesis and progression of CRC 2To facilitate the development of novel chemotherapeutic agents and 3 To gain the experience for the practice of evidence-based medicine
Detailed Description:
Stage IV disease represented approximately 25 of all colorectal cancer CRC cases The mainstay treatment for stage IV CRC is chemotherapy and surgery is only for palliation of symptoms including colorectal bleeding and obstruction If patients with stage IV CRC were not treated the average survival time was 6 months Recently with the progress of chemotherapeutic agents such as oxaliplatin and irinotecan the stage IV patients average survival time considerably increased to 18 months However the currently utilized chemotherapeutic regimens including FOLFOX Folinic acid 5-Fu oxaliplatin and FOLFIRI Folinic acid 5-Fu irinotecan their response rate was only around 50-60 Moreover these agents had several severe side-effects such as neurotoxicity and diarrhea Therefore it is mandatory for us to seek clinicopathogical parameters or novel molecular markers that predicted chemosensitivity in terms of increase of response rate and avoidance of side-effects Recently the carcinogenesis of CRC was better clarified than before Some molecular markers such as p53 K-ras microsatellite instability MSI microvessel densityMVD and epidermal growth factor receptorEGFR and their relation to survival of colorectal cancer patients have become the focus of research
The present project basically follows our previous study that p53 overexpression predict poorer chemosensitivityLiang et al Int J Cancer 2002 97 451-457 and we plan to further explore the association between chemosensitivity with MSI-H MVD and EGFR In fact in either FOLFOX or FOLFIRI they all belong to 5-Fu-based therapy Therefore the tumor expression of enzymes related to the metabolism of 5-Fu such as thymidylate synthaseTSand dipyrimidine dehydrogenaseDPD have also become the hot issue of research In this project we will explore the clinical implications of MSI TS DPD MVD and EGFR This is because our previous study has indicated that MSI-H is a marker of mutator phenotype of colorectal cancer ie colorectal cancers with MSI-H tend to have multiple mutations of downstream genes especially those with repetitive microsatellite sequences within the genes Our previous study has shown MSI-H predicted better chemosensitivityLiang et al Int J Cancer 2002 101 519-525 Therefore we are curious to know that if MSI-H is related to the alterations of TS and DPD in the tumor ie if the alterations for the tumor levels of TS and DPD is one of the mechanisms for the better chemosensitivity in tumors with MSI-H On the other hand it has been known that EGFR is related to tumor growth invasion angiogenesis and metastasis of colorectal cancers Therefore it is mandatory to further dissect the correlation between EGFR and MVD To the best of our knowledge this has not been published before
The present project will follow our previous phaseⅡ study of FOLFOX regimens for the treatment of stage Ⅳ colorectal cancer We will recruit at least 200 patients for this study The selection of patients will be based on rigorous eligibility criteria The patients will be allocated based on the expression of each molecular marker and the implementation of chemotherapy For example in the examination for the clinical implications of EGFR the patients will be classified into four groups EGFR chemotherapy EGFR chemotherapy- EGFR- chemotherapy EGFR- chemotherapy- Base on the analysis of this 22 table we will clarify the prognostic significance of a specific molecular marker is due to whether the specific molecular marker predicts biological invasiveness andor chemosensitivity After the analysis of prognostic significance of each molecular marker we will explore the interrelationship between these molecular markers Also all these 5 molecular markers and various clinicopathological factors will be subjected to multivariate analysis Because the survival of stage Ⅳ CRC patients will generally not exceed 30 months the patients study will not have to be followed up for a long time before the final study result appears We believe the present study will have the following significance 1To further clarify the mechanisms for the carcinogenesis and progression of CRC 2To facilitate the development of novel chemotherapeutic agents and 3 To gain the experience for the practice of evidence-based medicine
The present project basically follows our previous study that p53 overexpression predict poorer chemosensitivityLiang et al Int J Cancer 2002 97 451-457 and we plan to further explore the association between chemosensitivity with MSI-H MVD and EGFR In fact in either FOLFOX or FOLFIRI they all belong to 5-Fu-based therapy Therefore the tumor expression of enzymes related to the metabolism of 5-Fu such as thymidylate synthaseTSand dipyrimidine dehydrogenaseDPD have also become the hot issue of research In this project we will explore the clinical implications of MSI TS DPD MVD and EGFR This is because our previous study has indicated that MSI-H is a marker of mutator phenotype of colorectal cancer ie colorectal cancers with MSI-H tend to have multiple mutations of downstream genes especially those with repetitive microsatellite sequences within the genes Our previous study has shown MSI-H predicted better chemosensitivityLiang et al Int J Cancer 2002 101 519-525 Therefore we are curious to know that if MSI-H is related to the alterations of TS and DPD in the tumor ie if the alterations for the tumor levels of TS and DPD is one of the mechanisms for the better chemosensitivity in tumors with MSI-H On the other hand it has been known that EGFR is related to tumor growth invasion angiogenesis and metastasis of colorectal cancers Therefore it is mandatory to further dissect the correlation between EGFR and MVD To the best of our knowledge this has not been published before
The present project will follow our previous phaseⅡ study of FOLFOX regimens for the treatment of stage Ⅳ colorectal cancer We will recruit at least 200 patients for this study The selection of patients will be based on rigorous eligibility criteria The patients will be allocated based on the expression of each molecular marker and the implementation of chemotherapy For example in the examination for the clinical implications of EGFR the patients will be classified into four groups EGFR chemotherapy EGFR chemotherapy- EGFR- chemotherapy EGFR- chemotherapy- Base on the analysis of this 22 table we will clarify the prognostic significance of a specific molecular marker is due to whether the specific molecular marker predicts biological invasiveness andor chemosensitivity After the analysis of prognostic significance of each molecular marker we will explore the interrelationship between these molecular markers Also all these 5 molecular markers and various clinicopathological factors will be subjected to multivariate analysis Because the survival of stage Ⅳ CRC patients will generally not exceed 30 months the patients study will not have to be followed up for a long time before the final study result appears We believe the present study will have the following significance 1To further clarify the mechanisms for the carcinogenesis and progression of CRC 2To facilitate the development of novel chemotherapeutic agents and 3 To gain the experience for the practice of evidence-based medicine
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