Gut Microbiome in Colorectal Cancer

Study Overview
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Brief Summary
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This is a pilot feasibility study designed to investigate the alterations in the gut microbiome that occur during the course of treatment for colorectal cancer

Detailed Description
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This is a pilot feasibility study designed to investigate the alterations in the gut microbiome that occur during the course of treatment for colorectal cancer (CRC). Three patient cohorts will be followed. Cohort A: patients treated with oral fluoropyrimidine CAP as part of standard of care (SOC) chemotherapy. Cohort B: patients treated with TAS-102 including those receiving it in combination with Y-90 radioembolization as part of a clinical trial. Cohort C: patients receiving CAP plus immunotherapy (pembrolizumab) and bevacizumab as part of a clinical trial. Investigators will replace participants as needed to ensure a minimum of 10 evaluable participants per cohort (or minimum total of 30 evaluable patients). Evaluable participants are defined as patients with two analyzable stool samples including a baseline sample and at least one on-treatment sample to be used in endpoint analysis

Official Title
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Gut Microbiome and Oral Fluoropyrimidine Study in Patients With Colorectal Cancer

Conditions
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Gastrointestinal Microbiome, Neoplasm, Colorectal

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has histologically proven colorectal adenocarcinoma The patient is starting treatment with oral fluoropyrimidine therapy: CAP or TAS-102 as SOC or on a clinical trial. This also includes those patients receiving treatment in the adjuvant setting or post-metastasectomy with no evidence of disease on imaging. Combination of oral fluoropyrimidine with other cancer-directed therapies, including oxaliplatin, bevacizumab, Y-90 radioembolization, or immunotherapy checkpoint inhibitors, is permitted. Combination of CAP with concurrent radiation is permitted, including patients undergoing radiotherapy to a rectal primary or a metastatic site. Male or female patient aged 18 years of age or older at the time of obtaining the signed and dated informed consent (no upper age limit). Be able to read and speak English. Be willing and able to provide written informed consent for the study Exclusion Criteria: Patient has had prior chemotherapy, biologic or immunotherapy in the previous 2 weeks. Patient has completed a course of antibiotics longer than 2 weeks in preceding six months or a course of antibiotics of any duration in the 4 weeks prior to starting oral chemotherapy. Any patient who requires treatment with antibiotics during the study may be removed at the investigator's discretion. Known HIV positive.

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 |
| --- | --- |
| Cohort A<br>Patients treated with oral fluoropyrimidine (Capecitabine (CAP)) as part of standard of care (SOC) chemotherapy | |
| Cohort B<br>Patients treated with Trifluridine/Tipiracil (TAS-102) including those receiving it in combination with Y-90 radioembolization as part of a clinical trial | |
| Cohort C<br>Patients receiving CAP plus immunotherapy (pembrolizumab) and bevacizumab as part of a clinical trial. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate rate (percentage of patients approached that consent to participate) | Feasibility and acceptability will be assessed by evaluating percentage of patients approached that consent to participate | Up to 2 years | 
| Reasons for nonparticipation/non-continuation of the study and adherence of submission of stool specimens | Feasibility and acceptability will be assessed by evaluating reasons for nonparticipation/non-continuation of the study and adherence of submission of stool specimens | Up to 2 years | 
| Dietary Assessment Questionnaires | Baseline questionnaires regarding bowel habits and dietary history. Patients will complete a 3-day diet record (Automated SelfAdministered 24-Hour (ASA24®) Dietary Assessment Tool or on paper) at the beginning of each treatment cycle when stool is collected. For mid-cycle or toxicity-related stool collections, patients will complete a 24-hour diet recall using the ASA24 system | Baseline, Day 1, Day 3, Day 7, Day 14, Day 21, at discontinuation of treatment (an average of 6 months) | 
| Acceptability of specimens for analysis | Specimens collected via Fecal occult blood test (FOBT) card method will be verified as evaluable defined as patients with two analyzable stool samples including a baseline sample and at least one on-treatment sample to be used in endpoint analysis. | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut microbiome diversity | Changes in the gut microbiome will be assessed by comparing the bacterial diversity present in the baseline pre-treatment stool sample to the designated initial treatment cycle midpoint for each of the three patient cohorts | Up to 2 years | 
| Change in relative abundance of following gut bacteria that occur with oral fluoropyrimidine therapy | Changes in relative and absolute abundance of specific bacteria from the Fusobacterium and Porphyromonas genus, and the species Bacteroides fragilis will be assessed using quantitative polymerase chain reaction (qPCR) and genus-specific primers | Up to 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, Oral Fluoropyrimidine