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

April 25, 2022 updated by: VastBiome
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Kentucky
      • Elizabethtown, Kentucky, United States, 42701
        • Recruiting
        • Baptist Health Clinical Research
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The investigator propose to enroll 800 cancer patients (NSCLC, MM, RCC, and TNBC; any stage) who are about to begin standard of care ICI therapy into a multi-site prospective observational study of the gut microbiome.

Description

Inclusion Criteria:

  1. Men or women ≥18 years of age
  2. 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
  3. Diagnosed with stages I-IV primary NSCLC, MM, TNBC or RCC
  4. 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
  5. Able to provide informed consent and answer study questionnaires in either English or Spanish
  6. Able to provide stool specimens for research purposes

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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) ]

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)
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.
Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)
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).
Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VastBiome

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 22, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 14, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 14, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 2, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 27, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00054854

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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