Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00201331
Status:
UNKNOWN
Last Update Posted:
2005-12-16
First Post:
2005-09-13
Brief Title:
Prospective Phase II Randomized Trial of Postoperative Adjuvant Chemotherapy in Patients With High Risk Colon Cancer
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
Prospective Phase II Randomized Trial of Postoperative Adjuvant Chemotherapy in Patients With High Risk Colon Cancer
Status:
UNKNOWN
Status Verified Date:
2005-12
Last Known Status:
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:
Based on the astonishing high response rate in metastatic colorectal cancer in weekly high dose 5-FU and leucovorin we will conduct a clinical trial to clarify the activity of this regimen in the adjuvant setting The regimen of 5-FU and high dose leucovorin administered as the schedule of INT-0089 will be chosen as the controlled arm which was proven as effective as standard 5-FU plus levamisole regimen with short duration of treatment21 In this study continuous infusion of 5-FU HDFL Arm B and bolus injection of 5-FU Arm A will be administered to the high risk colon cancerN2 disease patients The role of TS level and inhibition of TS as a predictor of adjuvant chemotherapy with 5-FU based treatment will be clearly defined prospectively
Detailed Description:
Approximately 75 of all patients with colon carcinoma present at a stage when all gross tumor can be surgically resected Despite that high resectability rate about 50 of all colon adenocarcinoma patients die of subsequent metastatic disease not apparent at surgery These individuals could benefit from adjuvant local or systemic chemotherapy
Based on the encouraging antitumor activity of 5-FU plus leucovorinLV in patients with metastatic colon carcinoma67 several investigators reported their results using this combination in the adjuvant setting Results of an NSABP C-038 suggested that postoperative 5-FU plus leucovorin reduces the risk of colon cancer recurrence by 30 and the associated mortality by 32 compared with MOFsemustine vincristine and 5-FU Recently investigators from the IMPACT group9 analyzed the role of adjuvant 5-FU plus high dose leucovorin given 5 days every 28 days for a total of six courses versus no treatment in patients with stage II or III colon cancer The treatment arm showed a significant reduction by 22 in mortality P0029 and a 35 reduction in relapse rate P00001 Preliminary results from other studies have also suggested benefits of 5-FU plus leucovorin as adjuvant treatment of colon cancer101112 Those studies had employed chemotherapy with 5-FU plus leucovorin although there were differences in duration of treatment and drug dose among those trials it is striking that all revealed a similar magnitude of benefit for adjuvant chemotherapy with 5-FU and leucovorin in node positive patients At the present time both 5-FU plus levamisole and 5-FU plus leucovorin can be considered acceptable adjuvant chemotherapy regimens for patients with node positive disease
Thymidylate synthaseTS is a critical therapeutic target for the fluoropyrimidine cytotoxic drugs that are the mainstay of the treatment for patients with advanced colorectal cancer TS provide the sole de nono source of thymidylate for DNA synthesis The clinical importance of TS in determining fluoropyrimidine cytotoxicity has been established in both clinical and preclinical study Increased expression of TS protein due to underlying gene amplification has been described in cell lines selected for drug resistance by exposure to 5-FU2223 Several investigators have also demonstrated that intratumoral TS activity are predictive for response to 5-FU24-26 High TS activity was associated with no response whereas a low TS activity was associated with good response to 5-FU
Based on the encouraging antitumor activity of 5-FU plus leucovorinLV in patients with metastatic colon carcinoma67 several investigators reported their results using this combination in the adjuvant setting Results of an NSABP C-038 suggested that postoperative 5-FU plus leucovorin reduces the risk of colon cancer recurrence by 30 and the associated mortality by 32 compared with MOFsemustine vincristine and 5-FU Recently investigators from the IMPACT group9 analyzed the role of adjuvant 5-FU plus high dose leucovorin given 5 days every 28 days for a total of six courses versus no treatment in patients with stage II or III colon cancer The treatment arm showed a significant reduction by 22 in mortality P0029 and a 35 reduction in relapse rate P00001 Preliminary results from other studies have also suggested benefits of 5-FU plus leucovorin as adjuvant treatment of colon cancer101112 Those studies had employed chemotherapy with 5-FU plus leucovorin although there were differences in duration of treatment and drug dose among those trials it is striking that all revealed a similar magnitude of benefit for adjuvant chemotherapy with 5-FU and leucovorin in node positive patients At the present time both 5-FU plus levamisole and 5-FU plus leucovorin can be considered acceptable adjuvant chemotherapy regimens for patients with node positive disease
Thymidylate synthaseTS is a critical therapeutic target for the fluoropyrimidine cytotoxic drugs that are the mainstay of the treatment for patients with advanced colorectal cancer TS provide the sole de nono source of thymidylate for DNA synthesis The clinical importance of TS in determining fluoropyrimidine cytotoxicity has been established in both clinical and preclinical study Increased expression of TS protein due to underlying gene amplification has been described in cell lines selected for drug resistance by exposure to 5-FU2223 Several investigators have also demonstrated that intratumoral TS activity are predictive for response to 5-FU24-26 High TS activity was associated with no response whereas a low TS activity was associated with good response to 5-FU
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