Gut Microbiome Dynamics in Metastasized or Irresectable Colorectal Cancer (GIMICC)

Gut Microbiome Dynamics in Metastasized or Irresectable Colorectal Cancer: Initiating a Prospective Multicenter Cohort (GIMICC)

In this study the characteristics and alterations of the gut microbiome during chemotherapy for metastasized or irresectable CRC are studied, as well as the relation between the gut microbiome and the effects of chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Diagnostic test: fecal sample; Behavioral: questionnaire; Diagnostic test: Blood sample

Detailed Description

Although systemic treatment for metastasized or irresectable colorectal cancer (CRC) is becoming increasingly effective, overall survival is still poor and side effects of current treatment modalities are substantial. There is an urgent need for novel therapies, and in addition, better predictive tools are needed to select the right drug to the right patient. New data suggest that modulation of the microbiome of the gut might provide opportunities to increase anti-tumor efficacy of immunotherapy. Whereas the relation between the gut microbiome and immunotherapy is intensively studied, the relation between the gut microbiome and efficacy of conventional chemotherapy is unknown. A better understanding of the composition, function and dynamics of the gut microbiome before and during chemotherapy might help to identify factors that can be influenced during the treatment of patients with metastasized or irresectable CRC.

Therefore, in this study the characteristics and alterations of the gut microbiome during chemotherapy for metastasized or irresectable CRC are studied, as well as the relation between the gut microbiome and the effects of chemotherapy.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: J. J. de Haan, MD, PhD; Phone Number: +31 50 3612821; Email: j.j.de.haan@umcg.nl
• Study Contact Backup: Name: D. J. de Groot, MD, PhD; Phone Number: +31 50 361 2821; Email: d.j.a.de.groot@umcg.nl

Study Locations

• Netherlands
  • Assen, Netherlands
    • Recruiting
    • Wilhelmina ziekenhuis
    • Contact: P. Nieboer, MD, PhD
  • Drachten, Netherlands
    • Recruiting
    • Ziekenhuis Nij Smellinghe
    • Contact: G. Bouma, MD
  • Emmen, Netherlands
    • Recruiting
    • TREANT zorggroep
    • Contact: C. Oldenhuis, MD, PhD
  • Enschede, Netherlands
    • Recruiting
    • Medisch Spectrum Twente
    • Contact: L. Mekenkamp, MD, PhD
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: D. J. de Groot, MD, PhD; Phone Number: +31 50 361 2821; Email: d.j.a.de.groot@umcg.nl
    • Contact: J. J. de Haan, MD, PhD; Phone Number: +31 50 361 6161; Email: j.j.de.haan@umcg.nl
    • Principal Investigator: J. J. de Haan, PhD
  • Groningen, Netherlands
    • Recruiting
    • Martini Ziekenhuis
    • Contact: J. van Rooijen, MD
  • Heerenveen, Netherlands
    • Recruiting
    • Tjongerschans Ziekenhuis
    • Contact: H. Bos, MD
  • Leeuwarden, Netherlands
    • Recruiting
    • Medisch Centrum Leeuwarden
    • Contact: B. Rikhof, MD, PhD
  • Scheemda, Netherlands
    • Recruiting
    • Ommelander Ziekenhuis Groep
    • Contact: R.R.H. van den Brom, MD, PhD
  • Sneek, Netherlands
    • Recruiting
    • Antonius Zorggroep
    • Contact: G. Veldhuis, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients who present in the hospitals of the North Netherlands Colorectal Cancer Network. The participating hospitals together cover 10% of the Dutch population. Given that 13.000 patients yearly are diagnosed with colorectal cancer of which one third will develop metastatic or irresectable disease (www.iknl.nl), in the hospitals participating in this study 400 potential patients will present. Taking into account that about 50% do not fulfil in- and exclusion criteria or will refuse to participate, about 200 patients per year are expected to be included.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients with histologically confirmed CRC with an indication for palliative systemic anti-tumor therapy (ANY combination of chemotherapy with/without anti-VEGF of anti-EGFR therapy)
• Measurable disease according to RECIST v1.1.
• Stored pathological specimens available
• Life expectancy ≥ 12 weeks
• Signed Informed Consent Form
• Ability to comply with protocol

Exclusion Criteria:

• Previous (neo)adjuvant chemotherapy < 6 months
• Previous radiotherapy on the small or large intestine < 1month
• Previous surgery of the small or large intestine < 1 month
• Uncontrolled inflammatory bowel disease
• Participation in a study with a potential effect on the gut microbiome

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

GIMICC; Adult patients with newly diagnosed metastasized or irresectable CRC with an indication for standard palliative systemic anti-tumor treatment.

Diagnostic test: fecal sample; patients will collect fecal samples at home prior to treatment and at 3 months after start of treatment at the time of response evaluation using a standard stool-collection-kit.; Behavioral: questionnaire; At the day of stool sampling, patients fill out a brief questionnaire about established factors that can change the microbiome such concurrent use of antibiotics and proton pump inhibitors.; Diagnostic test: Blood sample; 4 tubes of blood are collected prior to treatment and at 3 months after start of treatment at the time of response evaluation and sent to the UMCG for storage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of response to conventional systemic anti-tumor therapy conventional systemic anti-tumor therapy for metastatic or irresectable colorectal cancer	To determine which bacteria species in the microbiome predict response to conventional systemic anti-tumor therapy according to RECIST v1.1 for metastatic or irresectable colorectal cancer	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of serious side effects to conventional systemic anti-tumor therapy for metastatic or irresectable colorectal cancer	To determine which bacteria strains in the microbiome predict serious side effects (grade 3/4 according to CTCAE v4.03) to conventional systemic anti-tumor therapy for metastatic or irresectable colorectal cancer	2 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: J. J. de Haan, MD, PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2020
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 31, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: colorectal cancer; gut microbiome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 201900296

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No