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NCT Number: NCT05037825

The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

The microbiome has the potential to serve as a robust biomarker of clinical response to immunotherapy. Additionally, microbial manipulation, through diet, exercise, prebiotics, probiotics, or microbially-derived metabolites, may prove to be beneficial in promoting anti-tumor immune responses. However, large prospective studies in humans with longitudinal sample collection and standardized methods are needed to understand how microbiota and their byproducts affect cancer therapies, particularly among patients undergoing identical therapy but experiencing different outcomes. The proposed observational study builds upon these hypotheses by proposing a large cohort design to further assess the associations between the gut microbiota (composition and function), host immune system, and ICI treatment efficacy across multiple cancer types.

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Key information

Conditions

Non-Small-Cell Lung Carcinoma Adenocarcinoma Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Malignant Melanoma Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Renal Cell Carcinoma Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms Triple Negative Breast Neoplasms Triple-negative Breast Cancer Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Baptist Health Clinical Research

Elizabethtown, Kentucky, 42701, United States

Location status: Recruiting

Location contact

Diane Drobny, BSN, RN, OCN, CCRP

CONTACT

[email protected]

(270) 706-5470

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men or women ≥18 years of age
  • Screened negative for COVID-19 symptoms at time of consent, as per institutional policy and as applicable for the duration of the COVID-19 pandemic
  • Diagnosed with stages I-IV primary NSCLC, MM, TNBC or RCC
  • Plan to be treated at a partner cancer site with a checkpoint inhibitor (anti-PD-1, anti-PD-L1, or anti-CTLA-4) as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent
  • Able to provide informed consent and answer study questionnaires in either English or Spanish
  • Able to provide stool specimens for research purposes

Exclusion criteria

  • Mental incapacity
  • Incarcerated individuals
  • Pregnancy (by self-report of pregnancy status)
  • Experiencing active brain metastasis/metastases
  • Treatment with checkpoint inhibitor in off-label capacity or through a clinical/interventional trial
  • Active participation in an immuno-oncology clinical/interventional trial or pharma-sponsored observational study

Treatment and study plan

Checkpoint Inhibitor, Immune

Drug

anti-PD-1, anti-PD-L1, or anti-CTLA-4 as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent

Primary outcomes

  1. Change in microbiome composition from baseline to after Cycle 2 of checkpoint therapy (6-8 weeks) by analyzing longitudinally-collected stool specimens of 800 patients with primary NSCLC, MM, RCC, and TNBC

    Time frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 of checkpoint blockade immunotherapy (at approximately 6-8 weeks) ]

    Microbiome evaluation with whole metagenome shotgun sequencing to assess changes in the relative abundance of microbial taxa (measured as percentage abundance per microbial species and changes in percentage abundance between baseline and cycle 2 timepoints) in patients who are receiving checkpoint blockade immunotherapy as the standard of care

Secondary outcomes

  1. Microbiome samples correlation

    Time frame: Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)

    Definition of a correlation between the gut microbiome and circulating cytokines (specifically IL-2, IL-10, TNF-alpha, IFN-gamma, and G-CSF) and therapeutic response (defined using RECIST criteria).

  2. Microbiome correlation to blood biomarkers

    Time frame: Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)

    Definition of a correlation between the gut microbiome (measured as percent abundance of microbial taxa derived from whole-metagenome shotgun sequencing) and plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) in patients receiving checkpoint blockade immunotherapy.

  3. Blood samples correlation

    Time frame: Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)

    Definition of a correlation between plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) and therapeutic response (defined using RECIST criteria).

Study contacts

Contact information is provided by the study sponsor or research team.

Hanane Arib, MS

CONTACT

[email protected]

650-479-5539

Peter McCaffrey, MD

CONTACT

[email protected]

650-479-5539

Sponsors and collaborators

Lead sponsor

VastBiome

Industry

Registry information

Acronym: PARADIGM

Important dates

Study start
2021
Primary completion
2023
Study completion
2028
First posted
Sep 8, 2021
Registry last updated
Apr 27, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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