PARADIGM: The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Sponsor

VastBiome (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05037825

Collaborator

(none)

800

Enrollment

Location

81.7

Anticipated Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Carcinoma Malignant Melanoma Renal Cell Carcinoma Triple-Negative Breast Cancer	Drug: Checkpoint Inhibitor, Immune

Study Design

Study Type:

Observational

Anticipated Enrollment :

800 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Actual Study Start Date :

Nov 22, 2021

Anticipated Primary Completion Date :

Sep 14, 2023

Anticipated Study Completion Date :

Sep 14, 2028

Outcome Measures

Primary Outcome Measures

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 [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 Outcome Measures

Microbiome samples correlation [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).
Microbiome correlation to blood biomarkers [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.
Blood samples correlation [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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