Gut Microbiome Dynamics in Metastasized or Irresectable Colorectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colorectal Cancer Metastatic

Intervention / Treatment
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* Diagnostic Test: fecal sample
* Behavioral: questionnaire
* Diagnostic Test: Blood sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GIMICC<br>Adult patients with newly diagnosed metastasized or irresectable CRC with an indication for standard palliative systemic anti-tumor treatment. | Diagnostic Test: fecal sample<br>* 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.<br>Behavioral: questionnaire<br>* 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.<br>Diagnostic Test: Blood sample<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiome, colorectal cancer