The Gut Microbiome and Immunotherapy Response in Solid Cancers

NCT ID: NCT06050733

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

16 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-06-30

Study Completion Date

2026-12-30

Brief Summary

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The aim of this study is characterize the gastrointestinal microbiomes of patient with solid cancer undergoing standard of care treatment with programmed cell death protein 1 (PD-1) /programmed cell death ligand (PD-L1) blockade.

Detailed Description

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Frontline treatment for solid cancers such as renal cell carcinoma includes immunotherapies such as immune checkpoint inhibitor (ICI) therapy. Despite an increase in overall survival in cancer patients undergoing ICI therapy, many patients' tumors are unresponsive or eventually progress. Recent studies indicate that the gut microbiome composition is associated with clinical response to ICI treatment. Following the success of preclinical research, two recent studies investigated the efficacy of fecal microbiota transplant (FMT) from cancer patients responsive to programmed cell-death protein 1 (PD-1) blockade, a type of ICI treatment, to patients nonresponsive to treatment. Notably, 30-40% of the FMT recipients in these studies subsequently responded to anti-PD-1 therapy. However, the effectiveness of FMT may vary among donors, there is no clear agreement on the ideal FMT composition, and FMT carries the risk of transmitting infection. An alternative to FMT is identification of specific efficacious commensals for supplementation. While the specific commensals enriched in cancer patients with more favorable outcomes vary from study to study, several are commonly reported, including Akkermansia muciniphila, Bacteroides spp., Bifidobacterium spp., Ruminococcaceae spp., and Faecalibacterium spp.

Cancer-related fatigue is experienced by nearly all patients during treatment, and cancer-related cognitive impairment (CRCI), which is a decrease in neurocognitive functioning that can be caused by cancer or its treatment, is present in up to ¾ of patients during treatment. Fatigue and CRCI have both been linked to the composition of the gut microbiome in cancer patients.

Specific Aims

Specific Aim 1: Characterize the gut microbiome of solid cancer patients that have had disease progression during standard-of-care treatment with PD-1 or programmed cell death ligand 1 (PD-L1) blockade and compare to solid cancer patients that were stable or experienced tumor shrinkage during standard-of-care treatment with PD-1/PD-L1 blockade.

Specific Aim 2: Assess neuropsychological measures of cognition and fatigue in solid cancer patients undergoing standard-of-care treatment with PD-1/PD-L1 blockade and determine associations with composition of the gut microbiome.

Conditions

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Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Solid cancer patients with disease progression

8 patients with a diagnosis of solid cancer undergoing standard of care treatment, with a PD-1 or PD-L1 inhibitor, with disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.

No interventions assigned to this group

Solid cancer patients with stable or experience shrinkage in tumor size

8 patients with a diagnosis of solid cancer undergoing standard of care treatment, with a PD-1 or PD-L1 inhibitor, with tumor size stable or shrinkage, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Current diagnosis of malignant solid cancer that is nonresectable or metastatic.
2. Ages 35 to 75 years.
3. Treatment with immunotherapy, specifically programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor, for at least 3 months but less than 24 months (except for previously responsive subjects re-enrolling as non-responsive patients).
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.
5. Participant is willing and able to give informed consent for participation in the study

Exclusion Criteria

1. Significant heart, liver, blood or respiratory disease.
2. Current diagnosis of HIV, Hepatitis B or Hepatitis C.
3. History of heart disease.
4. Uncontrolled diabetes mellitus.
5. Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
6. Females who are pregnant or lactating.
7. Treatment with chemotherapy within the past 2 years.
8. Treatment with kinase inhibitors within the past 3 months.
9. Previous radiation therapy for brain metastases.
10. Other medical condition or medication administration deemed exclusionary by the study investigators.
Minimum Eligible Age

35 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Melinda Sheffield-Moore, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

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University of Texas Medical Branch

Galveston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kristen McGovern, PhD

Role: CONTACT

Phone: 409-772-8126

Email: [email protected]

Kate Randolph, BS

Role: CONTACT

Phone: 409-223-7891

Email: [email protected]

Facility Contacts

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Kristen McGovern, PhD

Role: primary

Kate Randolph, BS

Role: backup

Other Identifiers

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23-0028

Identifier Type: -

Identifier Source: org_study_id