Ignite Creation Date:
2024-05-06 @ 6:24 PM
Last Modification Date:
2024-10-26 @ 2:47 PM
Study NCT ID:
NCT05655780
Status:
RECRUITING
Last Update Posted:
2023-01-11
First Post:
2022-12-08
Brief Title:
The Role of the Tumor Molecular Profile CMS UGT1A1 Genotype and Beta-glucuronidase Activity of the Intestinal Microbiota for Treatment Efficiency Toxicity Survival and Quality of Life in Patients With Metastatic or Unresectable Colorectal Cancer During Irinotecan-based Systemic Treatment
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
Optimal Survival and Quality of Life in Patients With Metastatic Colorectal Cancer With Irinotecan Dosing Based on UGT1A1 Genotype and Gut Microbiota Enzyme Activity Including a Dietary Intervention OPTIMA
Status:
RECRUITING
Status Verified Date:
2023-01
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:
Irinotecan-based systemic therapy is a treatment option for metastatic or unresectable colorectal cancer However this therapy has two major disadvantages namely an unpredictable response to the treatment and severe side effects for instance diarrhea or a low white blood cell count neutropenia Therefore the OPTIMA study was developed to find out if biomarkers such as the molecular profile of the tumor the UGT1A1 genotype and activity of the bacterial enzyme β-glucuronidase can predict response and side effects during irinotecan treatment By looking at these biomarkers treatments could be more personalized resulting into enhanced therapy efficiency increased optimal survival and a better quality of life
Detailed Description:
Irinotecan-based systemic therapy is shown to have promising results in metastatic or unresectable colorectal cancer However this therapy has two major disadvantages including an unpredictable individual treatment response and late-onset systemic and gastrointestinal toxicity To target these problems biomarkers are needed which could be used to predict treatment response and toxicity before start of the treatment The molecular profile of the tumor consensus molecular subtypes CMS the UGT1A1 genotype and the gut microbiota-derived enzyme β-glucuronidase are promising candidates in this context Recent research demonstrated that irinotecan-based systemic therapy increased both progression free survival PFS and optimal survival OS predominantly in patients with CMS4 cancers as well as in preclinical models representing this subtype For the other CMS subtypes CMS1-3 irinotecan-based systemic therapy was shown to be significantly less efficient For the UGT1A1 genotypes decreased activity of the UGT1A1 enzyme converting the toxic metabolite SN-38 into the inactive SN-38G will increase the concentration of toxic SN-38 resulting in systemic toxicity Lastly the importance of studying bacterial β-glucuronidase β-GUS activity in CRC patients during treatment with irinotecan can be derived from recent animal studies and indirect human evidence Previous research has shown that high bacterial β-GUS activity converting the inactive SN-38G into the toxic SN-38 might be a possible indicator for irinotecan-induced late-onset gastrointestinal toxicity due to SN-38 accumulation Therefore the OPTIMA study was developed to combine prediction of tumor sensitivity towards irinotecan by CMS classification UGT1A1 expression for irinotecan dose determination and β-GUS for risk assessment for late-onset gastrointestinal toxicity The aim of the study is to investigate whether the molecular profile of the tumor eg based on CMS the UGT1A1 genotype and β-GUS activity can act as a predictor for therapy efficiency late-onset systemic and gastrointestinal toxicity as well as OS and quality of life QoL
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None