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

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ClinicalTrials.gov Identifier: NCT03586297
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : July 2, 2021
Sponsor:
Collaborator:
Breast Cancer Research Foundation
Information provided by (Responsible Party):
Hackensack Meridian Health

Brief Summary:
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.

Condition or disease
Triple Negative Breast Cancer

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.

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Study Type : Observational
Estimated Enrollment : 49 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Gut and Intratumoral 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, 2022
Estimated Study Completion Date : May 1, 2023

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 is correlated with variability in the composition of intestinal and intratumoral 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. ]
    Determine whether the correlation between specific microbiota and the probability of pCR is predictive for the resolution of T cell exhaustion.

  2. 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.

  3. 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.


Biospecimen Retention:   Samples With DNA
Stool and Blood Specimens


Information from the National Library of Medicine

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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
Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT03586297


Contacts
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Contact: Sara Hyman, BA 551-996-4381 Sara.Hyman@hackensackmeridian.org

Locations
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United States, Connecticut
Yale University - Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520-8327
Contact: Rocco Carbone, MS    203-687-5885    rocco.carbone@yale.edu   
Contact: Rajni Mehta       rajni.mehta@yale.edu   
Principal Investigator: Lajos Pusztai, MD         
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Contact: Caroline Jackman    202-687-8469    cj514@georgetown.edu   
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    Sara.Hyman@hackensackmeridian.org   
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
Investigators
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Principal Investigator: Leslie Montgomery, MD Hackensack UMC
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Responsible Party: Hackensack Meridian Health
ClinicalTrials.gov Identifier: NCT03586297    
Other Study ID Numbers: BCRF 2017
PRO2017-0331 ( Other Identifier: HackensackUMC )
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: July 2, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hackensack Meridian Health:
BCRF
Microbiome
Intratumoal microbiota
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases