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 (OPTIMA)

May 16, 2025 updated by: Maastricht University Medical Center

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 (e.g. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
104

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Recruiting
        • Maastricht UMC+
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

A total of 104 participants will be included for this study. The patients will be addressed for participation in several hospitals in the Netherlands, including the Maastricht University Medical Centre+, Catharina Hospital, Amsterdam UMC, Hospital Gelderse Vallei, Van Weel-Bethesda Hospital and VieCuri Hospital. All participants are asked to sign an informed consent.

Description

Inclusion Criteria:

  • Adult patient: 18 years of age or older
  • Patients diagnosed with metastatic or unresectable CRC, who will be treated with irinotecan-based systemic therapy with or without anti-eGFR treatment.
  • WHO performance status 0-2

  • Minimal acceptable safety laboratory values defined as:

    • ANC of ≥ 1.5 x 109 /L
    • Platelet count of ≥ 100 x 109 /L
    • Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 2.5 x ULN; in case of liver metastases ALAT and ASAT ≤ 5 x ULN.
    • Renal function (eGFR) ≥ 50 ml/min or OR creatinine ≤ 1.5 x ULN
  • Written informed consent

Exclusion Criteria:

  • Microsatellite instability (MSI) or deficient MMR proteins
  • Pregnant or nursing
  • Presence of ileostomy
  • Asian ethnicity
  • Other systemic treatment is less than one month before the start of the irinotecan-based treatment
  • Therapeutic antibiotic use is less than three months before the start of the irinotecan-based treatment
  • Abdominal radiotherapy is less than two weeks before the start of the irinotecan-based treatment
  • Physically or mentally incapable or incompetent
  • More than 25% irinotecan dose reduction at the start of treatment (dose reductions during treatment are allowed), with exception of dose reduction due to UGT1A1 mutation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Bacterial beta-glucuronidase activity
Time Frame: 2022-2028
Bacterial beta-glucuronidase activity will be measured in faecal samples by using a validated beta-glucuronidase enzyme activity assay, which is based on previous studies. If we measure beta-glucuronidase activity, we will be able to predict late-onset gastrointestinal toxicity because we can estimate the amount of toxic SN-38 that will be produced.
2022-2028
UGT1A1 (uridine diphosphate glucuronosyltransferase)
Time Frame: 2022-2028
UGT1A1 will be measured by using blood samples, since decreased activity of the UGT1A1 enzyme will ensure an increase in toxic SN-38. When we measure the activity of the UGT1A1 enzyme, we can adjust the treatment dose based on this and, consequently, reduce gastrointestinal toxicity.
2022-2028
Molecular profile of the tumor
Time Frame: 2022-2028
Associations between the baseline molecular profile of the tumor (e.g. CMS) and response to irinotecan-based treatment
2022-2028

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Maastricht University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Erasmus Medical Center
Maastricht University
Gelderse Vallei Hospital
Dutch Colorectal Cancer Group (DCCG)
Clinical Trial Center Maastricht B.V.
Danone Nutricia Research
Wageningen University & Research
Fontys Hogeschool
Amsterdam UMC - Locatie AMC
Catharina Ziekenhuis
University of North Carolina (USA)
Oncology patientenpanel MUMC
Stichting Kanker.nl
Van Weel-Bethesda Ziekenhuis
VieCuri Medisch Centrum voor Noord-Limburg
Prospectief Landelijk CRC Cohort (PLCRC)
CRC-guideline committee
CZ zorgverzekeraar
Landelijke Werkgroep Diëtisten Oncologie (LWDO)
Rode Kruis Ziekenhuis Beverwijk

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marjolein Smidt, Prof. dr., Maastricht University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 9, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 19, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 18, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • METC 2022-3247

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings