Intestinal Microbiome Modification With Resistant Starch in Patients Treated With Dual Immune Checkpoint Inhibitors

Pilot Study of Intestinal Microbiome Modification With Resistant Starch in Patients Treated With Dual Immune Checkpoint Inhibitors

This is a pilot study designed to assess the safety and feasibility of administering a dietary supplement to patients undergoing cancer treatment with a dual immune checkpoint inhibitors (ICIs) for solid cancer.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Potato starch

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients starting dual immune checkpoint inhibitor therapy (ipilimumab and nivolumab in any dose combination) for solid cancer treatment per FDA approved indications.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Patients with a history of colectomy and/or gastric bypass.
• Patients with a known diagnosis of inflammatory bowel disease or irritable bowel syndrome.
• Patients with active Clostridium difficile infection. Active infection is defined as a stool sample positive for Clostridium difficile toxin by EIA and either symptoms (frequent loose stools) OR imaging findings consistent with toxic megacolon.
• Inability to take oral supplements
• Patients with existing gastrointestinal symptoms including abdominal pain, diarrhea (watery stool), nausea and/or actively requiring regular anti-emetics.
• Patients with symptomatic bowel metastasis including pain, severe constipation, or gastrointestinal bleeding.
• Receiving antibiotic within 14 days of ICI therapy initiation.
• Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient or raise concern that the patient would not comply with protocol procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Potato-based dietary starch supplement; Patients undergoing cancer treatment with dual immune checkpoint inhibitors (ICI) will receive potato-based dietary starch supplements.	Drug: Potato starch; Starting 5-7 days before treatment with dual-ICI, participant will consume 20g of potato starch (Bob's Red Mill®) once a day for 3 days, then increase to 20g twice a day, continuing throughout dual-ICI treatment (total duration approximately 13 weeks).; Other Names: Resistant starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients able to adhere to resistant starch (RS) supplement schedule	Feasibility will be determined by calculating the number of patients who have taken 70% or more of scheduled dose of dietary intervention. Patients will be asked to record doses of starch taken and will be provided a table in which doses can be checked off.	Approximately 13 weeks
Frequency of serious adverse events (SAEs) attributable to ICI therapy	Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency of known serious effects of ICIs will be compared to historical rates.	Up to 6 months (3 months after RS supplement discontinuation)
Occurrence of unanticipated serious adverse events (SAEs)	Adverse events will be assessed using the NCI CTCAE, version 5.0.	Approximately 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of immunotherapy-induced diarrhea/colitis	Graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	Up to 6 months (3 months after RS supplement discontinuation)
Change in luminal microbiome composition	Weekly stool samples will be compared to the baseline sample (prior to starting starch-based dietary supplement). Stool samples will be analyzed for microbial nucleic acids to characterize the components of the stool microbiome.	Up to 6 months (3 months after RS supplement discontinuation)
Change in luminal microbiome metabolite	Weekly stool samples will be compared to the baseline sample (prior to starting starch-based dietary supplement). Key metabolic byproducts will be identified in stool specimens using liquid chromatography and mass spectrometry.	Up to 6 months (3 months after RS supplement discontinuation)

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Leslie Fecher, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Actual): January 24, 2023
• Study Completion (Actual): January 24, 2023

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Immune checkpoint inhibitor
• Other Study ID Numbers: UMCC 2020.010; HUM00178229 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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