Gut Microbiome in Colorectal Cancer (GO)

Gut Microbiome and Oral Fluoropyrimidine Study in Patients With Colorectal Cancer

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

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Microbiome; Neoplasm, Colorectal

Detailed Description

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

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Recruitment will include both patients who will be taking TAS-102 and those taking CAP with or without other cancer-directed therapies, including those receiving CAP in combination with concurrent rectal radiation. Patients with colorectal cancer (CRC) expected to receive CAP or TAS-102 will be screened by the study PI, co-investigators, or study coordinators. The study coordinator may identify potential participants by various mechanisms: direct referral from a treating physician, review of schedules of medical and oncology providers at UCSF and participating sites, or phone calls from patients or referring physicians.

Description

Inclusion Criteria:

1. The patient has histologically proven colorectal adenocarcinoma
2. 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.
3. Combination of oral fluoropyrimidine with other cancer-directed therapies, including oxaliplatin, bevacizumab, Y-90 radioembolization, or immunotherapy checkpoint inhibitors, is permitted.
4. Combination of CAP with concurrent radiation is permitted, including patients undergoing radiotherapy to a rectal primary or a metastatic site.
5. 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).
6. Be able to read and speak English.
7. Be willing and able to provide written informed consent for the study

Exclusion Criteria:

1. Patient has had prior chemotherapy, biologic or immunotherapy in the previous 2 weeks.
2. 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.
3. Known HIV positive.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cohort A; Patients treated with oral fluoropyrimidine (Capecitabine (CAP)) as part of standard of care (SOC) chemotherapy
Cohort B; 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; Patients receiving CAP plus immunotherapy (pembrolizumab) and bevacizumab as part of a clinical trial.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Wesley Kidder, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2018
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: July 18, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Gut Microbiome; Oral Fluoropyrimidine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 174527; R21CA227232 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified data will be shared with researchers at other institutions.

Drug and device information, study documents

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