Gut and Intratumoral Microbiome Effect on the Neoadjuvant Chemotherapy-induced Immunosurveillance in Triple Negative Breast Cancer

January 8, 2024 updated by: Hackensack Meridian Health
The probability of pCR in TNBC patients receiving standard of care neoadjuvant chemotherapy treatment is associated with the dominance of specific intestinal and intratumoral microbiota that promote anti-tumor immunosurveillance.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This is a prospective study of newly diagnosed triple negative breast cancer (TNBC) patients undergoing standard of care neoadjuvant chemotherapy and correlate gut and intratumoral microbiome composition and anti-tumor immune responses with pCR.

The biopsy at diagnosis will be used as a pretreatment control for the assessment of TILs, PD-L1 expression, immune signature profiles. Both tumor and "normal" adjacent non-tumor tissue will be evaluated. Stool and peripheral blood (PB) samples will be collected at time of consent for therapy. TNBC patients will be treated with the standard of care neoadjuvant chemotherapy. At mid-treatment (MT), an elective tumor biopsy will be performed and stool and PB samples will be collected. At time of surgery, after the completion of neoadjuvant chemotherapy (at the discretion of the medical oncologist), resected tumor and "normal" adjacent non-tumor tissue, stool and PB samples will be collected.

Pre- , mid- and post-therapy immune phenotyping/profiling will be determined in PB samples and patient biopsies. The overall composition of the gut microbiome will also be determined in patient stool samples.

The overview of the study is presented below:

  1. Regimen and duration of neoadjuvant chemotherapy is at the discretion of the medical oncologist.
  2. Cycle 1 refers to first dose of each treatment.
  3. Tumor morphology, IHC and FISH will be performed at diagnosis of TNBC. Criteria for newly diagnosed TNBC: <1% of ER and PR immunoreactivity and HER2- by FISH or IHC staining 0 or 1+ and T1 (T1: <1.5 cm) mass lesion or greater.
  4. For correlative studies, collection of PB will be at day 1 of cycle 1, day 1 of cycle 1 of T and end of treatment, prior to surgery. Eight 8x tubes, seven (7) yellow top tubes (BD Vacutainer ACD Solution A Blood Collection tubes - 8.5ml) and one (1) Streck tube . Immunophenotying, gene expression profiling and assessment of cytokine/chemokine and other mediators production will be performed.
  5. For correlative studies, Stool collection will be collected up to 48 hours prior to drug administration on day 1 of cycle 1 and day of surgery. Sequencing of the gut and intratumoral microbiome and gene-associated pathways will be performed by 16S rRNA and shotgun metagenomics sequencing.
  6. For correlative studies, immunostaining of fixed tissue for PD-L1 or other immune marker expression on tumor cells and for the in situ presence of various T cell subset markers with PD1 expression will be performed. Isolation of DNA and RNA will be performed from formalin-fixed tissues.
  7. Tumor biopsy for mid-treatment (MT). This biopsy will be offered and performed upon consent of patient.
  8. This tissue will be provided by Pathology Department upon processing of surgical specimen.

Study Type

Observational

Enrollment (Estimated)

49

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 Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8327
        • Recruiting
        • Yale University - Yale Cancer Center
        • Principal Investigator:
          • Lajos Pusztai, MD
        • Contact:
        • Contact:
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Recruiting
        • Georgetown University
        • Principal Investigator:
          • Candace Mainor, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack Meridian Health
        • Sub-Investigator:
          • Rena Feinman, PhD
        • Sub-Investigator:
          • Deena Graham, MD
        • Sub-Investigator:
          • Gail Starr, MD
        • Sub-Investigator:
          • Oliver Loudig, PhD
        • Principal Investigator:
          • Marson Davidson, MD
        • Sub-Investigator:
          • Stanley Waintraub, MD
        • Sub-Investigator:
          • Donna McNamara, MD
        • 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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Newly Diagnosed Triple Negative Breast Cancer Patients

Description

Inclusion Criteria:

  • Histologically confirmed new diagnosis of TNBC (<5% of ER and PR immunoreactivity and HER2- by FISH or IHC staining 0 or 1+)
  • >18 years
  • 1.5 cm mass lesion or greater
  • Tumor amenable to percutaneous core biopsy

Exclusion Criteria:

  • chronic anticoagulation therapy
  • prior ipsilateral breast surgery, ipsilateral radiotherapy, hormonal therapy or systemic chemotherapy
  • Prolonged antibiotic treatment > 10 days within 1 month of neoadjuvant chemotherapy as prevention or suppression of an ongoing infection
  • lactating
  • pregnant

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic Complete Response
Time Frame: completion of chemotherapy, approximately 18 weeks.
The primary objective of this study is to determine if the probability of pCR (pathologic complete response) in TNBC (triple negative breast cancer) patients treated with standard of care neoadjuvant chemotherapy is correlated with variability in the composition of intestinal and intratumoral microbiota and subsequent short-term alterations in that composition.
completion of chemotherapy, approximately 18 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Other Correlations between Pathologic complete Response
Time Frame: completion of chemotherapy, approximately 18 weeks.
Determine whether the correlation between specific microbiota and the probability of pCR is predictive for the resolution of T cell exhaustion.
completion of chemotherapy, approximately 18 weeks.
Other Correlations between Pathologic complete Response
Time Frame: completion of chemotherapy, approximately 18 weeks.
Determine if specific microbiota correlated with the probability of pCR are associated with the anti-tumor innate and adaptive immune responses in the tumor site and peripheral blood.
completion of chemotherapy, approximately 18 weeks.
Other Correlations between Pathologic complete Response
Time Frame: completion of chemotherapy, approximately 18 weeks.
Determine the predictive values of baseline tumor PD-L1 (Programmed death-ligand 1) expression and PD-1 and other immune checkpoint inhibitory markers in TILs (tumor infiltrating lymphocytes) with pCR.
completion of chemotherapy, approximately 18 weeks.

Collaborators and Investigators

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

Sponsor

Hackensack Meridian Health

Collaborators

Breast Cancer Research Foundation

Investigators

  • Principal Investigator: Marson Davidson, MD, Hackensack Meridian Health

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)

August 27, 2017

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

June 11, 2018

First Submitted That Met QC Criteria

July 2, 2018

First Posted (Actual)

July 13, 2018

Study Record Updates

Last Update Posted (Actual)

January 9, 2024

Last Update Submitted That Met QC Criteria

January 8, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCRF 2017
  • PRO2017-0331 (Other Identifier: HackensackUMC)

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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