Ignite Creation Date:
2024-05-06 @ 1:21 AM
Last Modification Date:
2024-10-26 @ 11:02 AM
Study NCT ID:
NCT01781403
Status:
COMPLETED
Last Update Posted:
2021-02-04
First Post:
2013-01-21
Brief Title:
Preoperative CRT With Temozolomide Plus Capecitabine in Rectal Cancer
Sponsor:
Asan Medical Center
Organization:
Asan Medical Center
Study Overview
Official Title:
Preoperative Chemoradiation With Capecitabine Plus Temozolomide in Patients With Locally Advanced Resectable Rectal Cancer Phase I Study
Status:
COMPLETED
Status Verified Date:
2021-01
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:
The investigators planned a phase I study of preoperative CRT with capecitabine plus temozolomide inpatients with locally advanced resectable rectal cancer 1 the role of temozolomide as a radiosensitizer has been well established 2 hypermethylation or low expression of MGMT promoter is associated with colorectal carcinogenesis can be found in 2040 of colorectal cancer patients and this proportion could be adequate for validation as its role of predictive biomarker and 3 temozolomide can be additive or synergistic because radiotherapy is now essential in the treatment of rectal cancer
Detailed Description:
Preoperative chemoradiation CRT with fluoropyrimidine 5-fluorouracil or capecitabine is now regarded as a standard treatment option in patients with locally advanced resectable rectal cancer and pathologic response rates and tumor regression grades after preoperative CRT have been proved to be important prognostic factors for survival outcomes Several studies of preoperative CRT with fluoropyrimidines plus other agents such as oxaliplatin irinotecan cetuximab and bevacizumab have been performed to improve pathologic response rates however they have failed to show improved results compared to those with fluoropyrimidine alone Thus fluoropyrimidine alone is a standard chemotherapeutic strategy in patients with locally advanced resectable rectal cancer who will be treated with preoperative CRT at present further studies are needed to find effective combination for improving pathologic responses other than fluoropyrimidines alone in these patient population
Temozolomide is an oral alkylating agent and has been proved to be effective in patients with glioblastoma or high grade anaplastic glioma when administered with concurrent radiotherapy either as adjuvant or recurrent settings and also seemed to be effective in patients with malignant melanoma either as monotherapy or combination chemotherapy Temozolomide has been known to deplete O6-methylguanine DNA methyltransferase MGMT which is one of the DNA repair enzymes and recent studies have shown that lower expression by immunohistochemistry or hypermethylation by methylation-specific PCR of MGMT could be a predictive marker of better responses to treatment with temozolomide in patient with glioblastoma high grade anaplastic glioma or malignant melanoma
Silencing of MGMT by promoter hypermethylation has been known to involve colorectal carcinogenesis pathway by the association with KRAS mutation and low-CIMP CpG island methylation phenotype and hypermethylation of MGMT promoter could be detected in 29 to 46 of tumor tissues from sporadic colorectal cancer patients Nagasaka et al showed notable results that MGMT promoter methylation status was associated with microsatellite instability and hypermethylation of MGMT promoter could be a predictive factor of low recurrence in colorectal cancer patients with adjuvant oral fluoropyrimidine chemotherapy after curative surgery In addition Shacham-Shmueli et al showed that temozolomide could be an additional treatment option in a small group of patients with chemotherapy-refractory metastatic colorectal cancer which had lower MGMT expressions
Temozolomide is an oral alkylating agent and has been proved to be effective in patients with glioblastoma or high grade anaplastic glioma when administered with concurrent radiotherapy either as adjuvant or recurrent settings and also seemed to be effective in patients with malignant melanoma either as monotherapy or combination chemotherapy Temozolomide has been known to deplete O6-methylguanine DNA methyltransferase MGMT which is one of the DNA repair enzymes and recent studies have shown that lower expression by immunohistochemistry or hypermethylation by methylation-specific PCR of MGMT could be a predictive marker of better responses to treatment with temozolomide in patient with glioblastoma high grade anaplastic glioma or malignant melanoma
Silencing of MGMT by promoter hypermethylation has been known to involve colorectal carcinogenesis pathway by the association with KRAS mutation and low-CIMP CpG island methylation phenotype and hypermethylation of MGMT promoter could be detected in 29 to 46 of tumor tissues from sporadic colorectal cancer patients Nagasaka et al showed notable results that MGMT promoter methylation status was associated with microsatellite instability and hypermethylation of MGMT promoter could be a predictive factor of low recurrence in colorectal cancer patients with adjuvant oral fluoropyrimidine chemotherapy after curative surgery In addition Shacham-Shmueli et al showed that temozolomide could be an additional treatment option in a small group of patients with chemotherapy-refractory metastatic colorectal cancer which had lower MGMT expressions
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