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
|Condition or disease|
|Triple Negative Breast Cancer|
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:
- Regimen and duration of neoadjuvant chemotherapy is 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 T1 (T1: <1.5 cm) mass lesion or greater.
- 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.
- 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.
- 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.
- Tumor biopsy for mid-treatment (MT). 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 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|
- 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.
- 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.
- 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.
- 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
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
|Contact: Sara Hyman, BA||551-996-4381||Sara.Hyman@hackensackmeridian.org|
|United States, Connecticut|
|Yale University - Yale Cancer Center||Recruiting|
|New Haven, Connecticut, United States, 06520-8327|
|Contact: Rocco Carbone, MS 203-687-5885 firstname.lastname@example.org|
|Contact: Rajni Mehta email@example.com|
|Principal Investigator: Lajos Pusztai, MD|
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20057|
|Contact: Caroline Jackman 202-687-8469 firstname.lastname@example.org|
|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|