Ignite Creation Date:
2024-05-06 @ 2:50 AM
Last Modification Date:
2024-10-26 @ 11:24 AM
Study NCT ID:
NCT02138617
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-09-14
First Post:
2014-05-01
Brief Title:
Genotype-Directed Study Of Irinotecan Dosing In FOLFIRI BevacizumabTreated Metastatic Colorectal Cancer
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
Official Title:
Genotype-Directed Phase II Study Of Higher Dose Of Irinotecan In First-Line Metastatic Colorectal Cancer Patients Treated With Folfiri Plus Bevacizumab
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-09
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:
This study involves standard combination chemotherapy treatment for colon cancer 5-Fluorouracil 5FU leucovorin and irinotecan known as FOLFIRI plus bevacizumab Avastin The study is designed to test the FOLFIRI regimen based on certain characteristics of a persons genetic makeup or genes Genes are made of DNA and determine not only inherited traits or appearance hair and eye color height body type etc but also play an important role in health and how the body responds to illness and treatments for those illnesses
In this study the investigators will examine the relationship between a patients genes DNA or genotype and how the patients body breaks down and removes or metabolizes the anti-cancer drug irinotecan Circulating blood level of irinotecan plays an important role in how well this drug works against a patients cancer as well as the adverse side effects the patient may experience The current standard dose of irinotecan was determined in clinical trials without knowing individual genotypes and thus does not take into account a patients ability to metabolize irinotecan This means that based on one genotype the current standard dose of irinotecan may be correct or based on other genotypes the standard dose could result in lower and possibly less effective blood levels and result in significant under-dosing of irinotecan
Based on genotype the patient will be assigned to one of the following doses of irinotecan
180 mgm2 standard dose
260 mgm2
310 mgm2
The purpose of this research study is to determine if dosing irinotecan based on genotype is effective and safe for patients with colon cancer Patient genotype will be determined from a small sample of blood and a laboratory test or assay performed at UNC Laboratories For the purpose of this study this assay is new and considered to be investigational This means that the genotype assay used in this study has not yet been approved by the FDA for determining irinotecan dose levels in patients with colon cancer
In this study the investigators will examine the relationship between a patients genes DNA or genotype and how the patients body breaks down and removes or metabolizes the anti-cancer drug irinotecan Circulating blood level of irinotecan plays an important role in how well this drug works against a patients cancer as well as the adverse side effects the patient may experience The current standard dose of irinotecan was determined in clinical trials without knowing individual genotypes and thus does not take into account a patients ability to metabolize irinotecan This means that based on one genotype the current standard dose of irinotecan may be correct or based on other genotypes the standard dose could result in lower and possibly less effective blood levels and result in significant under-dosing of irinotecan
Based on genotype the patient will be assigned to one of the following doses of irinotecan
180 mgm2 standard dose
260 mgm2
310 mgm2
The purpose of this research study is to determine if dosing irinotecan based on genotype is effective and safe for patients with colon cancer Patient genotype will be determined from a small sample of blood and a laboratory test or assay performed at UNC Laboratories For the purpose of this study this assay is new and considered to be investigational This means that the genotype assay used in this study has not yet been approved by the FDA for determining irinotecan dose levels in patients with colon cancer
Detailed Description:
This phase II multicenter clinical trial will use a genotype-guided dosing strategy for irinotecan to prospectively analyze efficacy in 100 metastatic colorectal cancer patients mCRC receiving FOLFIRI 5-fluorouracil 5-FU leucovorin irinotecan plus bevacizumab Irinotecan is detoxified and excreted primarily by glucuronidation in the liver via the isoenzyme uridine diphosphate glucuronosyl transferase UGT1A1 Common variants in UGT1A1 alter the rate of glucuronidation and thus alter exposure to irinotecan
The UGT1A1 28 allele results in slower irinotecan glucuronidation and thus greater exposure to its active metabolite SN-38 At the standard irinotecan dose used in FOLFIRI 180 mgm2 established prior to our understanding of the importance of genotype in the rate of this drugs metabolism there is a small increased risk of neutropenia in 28 homozygotes However the risk of clinically important consequences of neutropenia such as febrile neutropenia and infection are not significantly increased Patients with other genotypes have a quite low risk of adverse effects suggesting patients with these low risk genotypes may tolerate higher doses of irinotecan in FOLFIRI This finding was demonstrated in a phase I study in which 128 and 11 genotypes were able to tolerate escalating doses of irinotecan up to 260 mgm2 and 310 mgm2 respectively
The central hypothesis of this trial is that increasing the irinotecan dose in 128 and 11 genotypes will increase the overall benefit of FOLFIRI for patients with mCRC as these two groups are likely under-dosed with the current dosing regimen Eligible patients will be genotyped for UGT1A1 and assigned into 1 of 3 different dosing groups based on their relative rate of metabolism The primary objective of this trial is to estimate progression-free survival PFS and secondary objectives include characterization of toxicity and objective response rate OR complete response CR partial response PR
The UGT1A1 28 allele results in slower irinotecan glucuronidation and thus greater exposure to its active metabolite SN-38 At the standard irinotecan dose used in FOLFIRI 180 mgm2 established prior to our understanding of the importance of genotype in the rate of this drugs metabolism there is a small increased risk of neutropenia in 28 homozygotes However the risk of clinically important consequences of neutropenia such as febrile neutropenia and infection are not significantly increased Patients with other genotypes have a quite low risk of adverse effects suggesting patients with these low risk genotypes may tolerate higher doses of irinotecan in FOLFIRI This finding was demonstrated in a phase I study in which 128 and 11 genotypes were able to tolerate escalating doses of irinotecan up to 260 mgm2 and 310 mgm2 respectively
The central hypothesis of this trial is that increasing the irinotecan dose in 128 and 11 genotypes will increase the overall benefit of FOLFIRI for patients with mCRC as these two groups are likely under-dosed with the current dosing regimen Eligible patients will be genotyped for UGT1A1 and assigned into 1 of 3 different dosing groups based on their relative rate of metabolism The primary objective of this trial is to estimate progression-free survival PFS and secondary objectives include characterization of toxicity and objective response rate OR complete response CR partial response PR
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