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Gut 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 : November 7, 2018
Sponsor:
Collaborator:
Breast Cancer Research Foundation
Information provided by (Responsible Party):
Hackensack Meridian Health

Tracking Information
First Submitted Date June 11, 2018
First Posted Date July 13, 2018
Last Update Posted Date November 7, 2018
Actual Study Start Date August 27, 2017
Estimated Primary Completion Date May 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 2, 2018)
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.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03586297 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 2, 2018)
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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Gut Microbiome Effect on the Neoadjuvant Chemotherapy-induced Immunosurveillance in Triple Negative Breast Cancer
Official Title Gut Microbiome Effect on the Neoadjuvant Chemotherapy-induced Immunosurveillance in Triple Negative Breast Cancer
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.
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Stool and Blood Specimens
Sampling Method Non-Probability Sample
Study Population Newly Diagnosed Triple Negative Breast Cancer Patients
Condition Triple Negative Breast Cancer
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 2, 2018)
49
Original Estimated Enrollment Same as current
Estimated Study Completion Date May 1, 2021
Estimated Primary Completion Date May 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Must be Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03586297
Other Study ID Numbers BCRF 2017
PRO2017-0331 ( Other Identifier: HackensackUMC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Hackensack Meridian Health
Study Sponsor Hackensack Meridian Health
Collaborators Breast Cancer Research Foundation
Investigators
Principal Investigator: Leslie Montgomery, MD Hackensack UMC
PRS Account Hackensack Meridian Health
Verification Date November 2018