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
|Condition or disease|
|Triple Negative Breast Cancer|
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:
- Duration of T treatment is 12 weekly cycles or at the discretion of the medical oncologist.
- Cycle 1 refers to first dose of each treatment.
- 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.
- 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.
- 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.
- 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.
- Tumor biopsy for cycle 1, day 1 of paclitaxel is not standard care. This biopsy will be offered and performed upon consent of patient.
- This tissue will be provided by Pathology Department upon processing of surgical specimen.
|Study Type :||Observational|
|Estimated Enrollment :||49 participants|
|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|
- 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.
- 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
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
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20057|
|Contact: Caroline Jackman 202-687-8469 email@example.com|
|Principal Investigator: Eleni Tousimis, MD|
|United States, New Jersey|
|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|
|Principal Investigator:||Leslie Montgomery, MD||Hackensack UMC|