Working... Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03586297
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : November 7, 2018
Breast Cancer Research Foundation
Information provided by (Responsible Party):
Hackensack Meridian Health

Brief Summary:
The probability of pCR in Triple Negative Breast Cancer patients receiving standard of care AC-T neoadjuvant chemotherapy is associated with the dominance of specific intestinal microbiota that promote anti-tumor immunosurveillance.

Condition or disease
Triple Negative Breast Cancer

Detailed Description:

This is a prospective study of newly diagnosed TNBC patients undergoing standard of care neoadjuvant chemotherapy and correlate gut 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. Stool and peripheral blood (PB) samples will be collected at time of consent for neoadjuvant therapy. Detailed instructions on the stool collection will be provided to patients (please see Appendix 1). TNBC patients will be first treated with 4 cycles of AC neoadjuvant chemotherapy (2 weeks/cycle). Prior to the initiation of T, a tumor biopsy will be offered to the patient. Patients that are interested in having the optional biopsy will be informed and will sign a separate consent form (please see Appendix 2). In addition to the samples collected, patients' information regarding their pathology and the diagnosis (and physicians' notes) will be reviewed.

Stool and PB samples will be collected. At time of surgery, after the completion of T (12 cycles, 1 week/cycle or at the discretion of the medical oncology), resected tumor and adjacent normal, non-tumor tissue, stool and PB samples will be collected.

Pre- 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. Duration of T treatment is 12 weekly cycles or 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 T2 mass lesion or greater.
  4. For correlative studies, collection of PB will be at day 1 of cycle 1 of AC, day 1 of cycle 1 of T and end of treatment, prior to surgery. 8x Yellow top tubes (BD Vacutainer ACD Solution A Blood Collection tubes — 8.5ml) — 68 ml. Immunophenotying, gene expression profiling and assessment of cytokine/chemokine 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 the gut 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 expression on tumor cells and for the in situ presence of various T cell subset markers with PD1 expression will be performed. Isolation of RNA will be performed from formalin-fixed tissues.
  7. Tumor biopsy for cycle 1, day 1 of paclitaxel is not standard care. 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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 49 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Gut Microbiome Effect on the Neoadjuvant Chemotherapy-induced Immunosurveillance in Triple Negative Breast Cancer
Actual Study Start Date : August 27, 2017
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Primary Outcome Measures :
  1. 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 doxorubicin/cyclophosphamide followed by paclitaxel (AC+T) is correlated with variability in the composition of intestinal microbiota and subsequent short-term alterations in that composition.

Secondary Outcome Measures :
  1. Other Correlations between Pathologic complete Response [ Time Frame: completion of chemotherapy, approximately 18 weeks. ]

    I. Determine whether the correlation between specific microbiota and the probability of pCR is predictive for the resolution of T cell exhaustion.

    II. Determine if specific gut 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.

    III. Determine the predictive values of baseline tumor PD-L1 (Programmed death-ligand 1) expression and PD-1 in TILs (tumor infiltrating lymphocytes) with pCR.

Biospecimen Retention:   Samples With DNA
Stool and Blood Specimens

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Must be Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Newly Diagnosed Triple Negative Breast Cancer Patients

Inclusion Criteria:

  • Histologically confirmed new diagnosis of TNBC (<1% of ER and PR immunoreactivity and HER2— by FISH or IHC staining 0 or 1+)
  • >18 years
  • T2 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
  • prior systemic antibiotics x 6 months
  • lactating
  • pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03586297

Layout table for location information
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Contact: Caroline Jackman    202-687-8469   
Principal Investigator: Eleni Tousimis, MD         
United States, New Jersey
Hackensack UMC Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Sara Hyman, BA    551-996-4381   
Principal Investigator: Leslie Montgomery, MD         
Sub-Investigator: Rena Feinman, PhD         
Sub-Investigator: Robert Korngold, PhD         
Sub-Investigator: Mary-Jane Warden, MD         
Sub-Investigator: Tara Balija, MD         
Sub-Investigator: Marson Davidson, MD         
Sub-Investigator: Deena Graham, MD         
Sub-Investigator: Gail Starr, MD         
Sub-Investigator: Ciaran Mannion, MD         
Sub-Investigator: Christopher Koenig, MD         
Sponsors and Collaborators
Hackensack Meridian Health
Breast Cancer Research Foundation
Layout table for investigator information
Principal Investigator: Leslie Montgomery, MD Hackensack UMC

Layout table for additonal information
Responsible Party: Hackensack Meridian Health Identifier: NCT03586297     History of Changes
Other Study ID Numbers: BCRF 2017
PRO2017-0331 ( Other Identifier: HackensackUMC )
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hackensack Meridian Health:

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases