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

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: Potato starch


Participation Criteria
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Eligibility Criteria
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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.

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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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Potato-based dietary starch supplement<br>Patients undergoing cancer treatment with dual immune checkpoint inhibitors (ICI) will receive potato-based dietary starch supplements. | Drug: Potato starch<br>* 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).<br>* Other names: Resistant starch;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune checkpoint inhibitor