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

NCT05655780 | Recruiting

• 1 other identifier: METC 2022-3247
• Study Type: observational
• Target: 104
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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

  2022-2028

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Maastricht University: collaborator
• Wageningen University & Research: collaborator
• Fontys Hogeschool: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Erasmus Medical Center: collaborator
• Catharina Ziekenhuis: collaborator
• University of North Carolina (USA): collaborator
• Oncology patientenpanel MUMC: collaborator
• Stichting Kanker.nl: collaborator
• Van Weel-Bethesda Ziekenhuis: collaborator
• VieCuri Medisch Centrum voor Noord-Limburg: collaborator
• Gelderse Vallei Hospital: collaborator
• Danone Nutricia Research: collaborator
• Clinical Trial Center Maastricht B.V.: collaborator
• Dutch Colorectal Cancer Group (DCCG): collaborator
• Prospectief Landelijk CRC Cohort (PLCRC): collaborator
• CRC-guideline committee: collaborator
• CZ zorgverzekeraar: collaborator
• Landelijke Werkgroep Diëtisten Oncologie (LWDO): collaborator
• Rode Kruis Ziekenhuis Beverwijk: collaborator

Study Sites (1)

Maastricht UMC+

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 40597074 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Marjolein Smidt, Prof. dr.

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janine Ziemons, M.Sc.

CONTACT

+31 (0)433881558; j.ziemons@maastrichtuniversity.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 19, 2022
• Study Start: January 9, 2023
• Primary Completion: October 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 18, 2025

Record last verified: 2025-05

Locations

NL (1)