Colorectal NeoplasmsOPTIMANCT05655780
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
An observational study of Colorectal Neoplasms, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- How many people
- 104 participants
- Where
- 1 siteNetherlands
- Study dates
- 9 Jan 2023to Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht UMC+
Maastricht, Limburg, 6229 HX
Marjolein Smidt, Prof. Dr., m.smidt@mumc.nl
About this study
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)
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.
Read the 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).
- Conditions
- Colorectal Neoplasms
- Medical subject headings
- Colorectal Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Bacterial beta-glucuronidase activity
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.
Measured: 2022-2028
UGT1A1 (uridine diphosphate glucuronosyltransferase)
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.
Measured: 2022-2028
Molecular profile of the tumor
Associations between the baseline molecular profile of the tumor (e.g. CMS) and response to irinotecan-based treatment
Measured: 2022-2028
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2022
- Study start9 Jan 2023
- Primary completionOct 2025 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University, Wageningen University & Research, Fontys Hogeschool, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Catharina Ziekenhuis, University of North Carolina, Oncology patientenpanel MUMC, Stichting Kanker.nl, Van Weel-Bethesda Ziekenhuis, VieCuri Medisch Centrum voor Noord-Limburg, Gelderse Vallei Hospital, Danone Nutricia Research, Clinical Trial Center Maastricht B.V., Dutch Colorectal Cancer Group, Prospectief Landelijk CRC Cohort (PLCRC), CRC-guideline committee, CZ zorgverzekeraar, Landelijke Werkgroep Diëtisten Oncologie (LWDO), Rode Kruis Ziekenhuis Beverwijk
- Responsible party
- Sponsor
- Investigators
- Marjolein Smidt, Prof. dr., Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05655780
- Sponsor's protocol ID
- METC 2022-3247
- Acronym
- OPTIMA
- Status last verified
- May 2025
- First submitted
- 8 Dec 2022
- Last updated
- 18 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Russ E, Ziemons J, Hillege LE, van Kuijk SMJ, de Jong EM, Elbers C, Deenen MJ, Borghuis LH, Bohm TMM, Kristen P, Valk LC, van Hellemond IEG, Vestjens H, Dietvorst A, Baars A, Goosens ANM, Vermeulen L, Buffart TE, de Vos-Geelen J, Penders J, Redinbo MR, Iersel LV, Smidt ML. Evaluation of potential biomarkers during irinotecan-based systemic treatment for colorectal cancer-study protocol of the OPTIMA study. BMC Cancer. 2025 Jul 1;25(1):1129. doi: 10.1186/s12885-025-14500-6.
PubMed 40597074
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05655780
- Acronym / sponsor ID
- OPTIMA / METC 2022-3247
- Conditions
- Colorectal Neoplasms
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Maastricht University, Wageningen University & Research, Fontys Hogeschool, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Catharina Ziekenhuis, University of North Carolina, Oncology patientenpanel MUMC, Stichting Kanker.nl, Van Weel-Bethesda Ziekenhuis, VieCuri Medisch Centrum voor Noord-Limburg, Gelderse Vallei Hospital, Danone Nutricia Research, Clinical Trial Center Maastricht B.V., Dutch Colorectal Cancer Group, Prospectief Landelijk CRC Cohort (PLCRC), CRC-guideline committee, CZ zorgverzekeraar, Landelijke Werkgroep Diëtisten Oncologie (LWDO), Rode Kruis Ziekenhuis Beverwijk
- Study start
- 9 Jan 2023 (actual)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 19 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- 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:
- Written informed consent
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2025.
- Derived from this study: PubMed 40597074Russ E, Ziemons J, Hillege LE, van Kuijk SMJ, de Jong EM, Elbers C, Deenen MJ, Borghuis LH, Bohm TMM, Kristen P, Valk LC, van Hellemond IEG, Vestjens H, Dietvorst A, Baars A, Goosens ANM, Vermeulen L, Buffart TE, de Vos-Geelen J, Penders J, Redinbo MR, Iersel LV, Smidt ML. Evaluation of potential biomarkers during irinotecan-based systemic treatment for colorectal cancer-study protocol of the OPTIMA study. BMC Cancer. 2025 Jul 1;25(1):1129. doi: 10.1186/s12885-025-14500-6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marjolein Smidt, Prof. dr. principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Neoplasms, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Janine Ziemons, M.Sc. (+31 (0)433881558, j.ziemons@maastrichtuniversity.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bacterial beta-glucuronidase activity (time frame: 2022-2028). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05655780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2025.