Clinical trial NCT03586297: Gut and Intratumoral Microbiome Effect on the Neoadjuvant Chemotherapy-induced Immunosurveillance in Triple Negative Breast Cancer
Official title: Gut and Intratumoral Microbiome Effect on the Neoadjuvant Chemotherapy-induced Immunosurveillance in Triple Negative Breast Cancer
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Triple Negative Breast Cancer
Keywords: BCRF
Microbiome
Intratumoal microbiota
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
Collaborators: name: Breast Cancer Research Foundation
First posted: 2018-07-13
Enrollment: 49
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly Diagnosed Triple Negative Breast Cancer Patients

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.

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.

Eligibility 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

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: completion of chemotherapy, approximately 18 weeks.
Secondary outcomes:
measure: Other Correlations between Pathologic complete Response
timeFrame: completion of chemotherapy, approximately 18 weeks.
measure: Other Correlations between Pathologic complete Response
timeFrame: completion of chemotherapy, approximately 18 weeks.
measure: Other Correlations between Pathologic complete Response
timeFrame: completion of chemotherapy, approximately 18 weeks.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University - Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
Study officials:
affiliation: Hackensack Meridian Health
name: Marson Davidson, MD
role: PRINCIPAL_INVESTIGATOR
References: