Trial Title:
TNBC Gut Microbiota During Neoadjuvant Treatment
NCT ID:
NCT06610097
Condition:
Breast Cancer
Triple Negative Breast Cancer
Early Stage Triple-Negative Breast Carcinoma
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Conditions: Keywords:
gut microbiome
triple-negative breast cancer
high fiber diet
immunotherapy
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Basic Science
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Other
Intervention name:
Nutritional Counseling
Description:
The nutritional intervention for the treatment group -- personalized counseling on
increasing fiber intake and maintaining adequate caloric intake during treatment -- will
be administered as (1) a 60-minute initial telehealth consultation within the first week
of study enrollment, and (2) up to two 30-minute follow-ups throughout the study, ideally
the first follow-up within 6 weeks of study enrollment. These sessions will be led by a
registered dietitian using cultural awareness and symptom assessment.
Arm group label:
High Fiber Dietary Counseling
Summary:
The gut microbiome is made up of the microbes (such as bacteria, viruses, and other
organisms too small to see with the naked eye) that live in the digestive tract and has
been shown to be important in metabolizing food, extracting vitamins and nutrients from
food, and maintaining a healthy gut lining. The gut microbiome plays an important role in
overall health and has been shown to dynamically change in response to early-stage
triple-negative breast cancer-directed therapies, which in turn has been associated with
worse outcomes. As the gut microbiome can be further modulated with dietary changes
during cancer treatment, it is an ideal potential modifiable risk factor in cancer
patients. However, due to multiple confounding factors such as dietary intake, mood, and
activity, its utility as part of the oncologic clinical assessment remains unclear.
In this prospective randomized controlled study, the investigators propose to recruit up
to 30 early-stage TNBC patients to randomize to a personalized nutritional intervention
of a high-fiber diet coached by a registered dietician versus educational handout alone
during neoadjuvant treatment. The investigators propose to study the gut microbiota
through stool sample analysis among early-stage triple-negative breast cancer patients
undergoing neoadjuvant (i.e. before surgery) chemotherapy +/- immunotherapy. The
investigators will also study how the gut microbiota can be further modulated with a
high-fiber diet, and the investigators hypothesize that a high-fiber diet may play a
protective role in preserving gut microbial diversity. As part of the nutritional
intervention, the investigators propose to administer nutritional counseling with a
registered dietitian (RD) to increase fiber intake and tracking performance status,
activity, and mood during neoadjuvant treatment. Finally, the investigators propose to
survey participants after study completion through one-on-one interviews to determine
whether participants experienced improved overall patient satisfaction in supportive care
during their treatment.
Detailed description:
This is a randomized, prospective study with a small group of 30 patients (pilot study).
Once participants are enrolled, they will be randomized in a 2:1 ratio of either the
nutritional intervention (personalized counseling on increasing fiber intake and
maintaining adequate caloric intake during breast cancer treatment) or an educational
handout on increasing fiber intake. Randomization will be concealed using a random number
generator. Investigators and healthcare providers will not be blinded due to the nature
of the intervention itself, but all documentation related to the personalized nutritional
intervention will not be part of the participant's electronic medical record.
Co-investigators completing the data analysis will be blinded to participants' group
assignments.
Consent will be obtained upon enrollment. Variables to be collected as part of the
baseline demographics questionnaire include: age, gender, marital status, education
level, employment status, annual income, residence (ZIP code), BMI, medications and dose,
TNBC stage at diagnosis, and treatment type(s).
Participants will complete: interim medication updates including antibiotic use (Interim
Survey), gastrointestinal symptoms using the PROMIS GI symptom assessment, dietary intake
(NCI-DSQ) with two 24-hour food logs, performance status (FACT-G Scale), anxiety (GAD-7),
and depression (PHQ-9), and physical activity (RAPA). If participants report
moderate-severe anxiety and/or depression through the GAD-7 and/or PHQ-9 surveys,
respectively, they will be notified by telephone or email to contact their primary care
provider or oncologist to seek prompt evaluation. Stool samples will be collected at
baseline (pre-treatment), 6-week, 12-week, 18-week, and 24-week timepoints. The 6-week
interval period was selected based on expected treatment cycles with dose-dense
doxorubicin/cyclophosphamide and Taxol +/- pembrolizumab. This interval was also selected
based on the minimum amount of time expected for potential changes in dietary intake and
symptoms during treatment. Survey reminders will be sent via the app every 6 weeks and
data will be exported to RedCap.
The nutritional intervention for the treatment group -- personalized counseling on
increasing fiber intake and maintaining adequate caloric intake during treatment -- will
be administered as (1) a 60-minute initial telehealth consultation within the first week
of study enrollment, and (2) up to two 30-minute follow-ups throughout the study, ideally
the first follow-up within 6 weeks of study enrollment. These sessions will be led by a
registered dietitian using cultural awareness and symptom assessment. Session notes will
be included in the participants' medical records. Control participants' intervention will
be an educational handout on increasing fiber intake. San Diego State University (SDSU)
masters students in Exercise and Nutritional Science will assist all participants with
completing two 24-hour ASA24 food logs at each timepoint along with other surveys.
Nutritional composition reported in 24-hour logs will be analyzed at SDSU using ASA24.
Participants will collect stool samples using the Zymo Research kit, which has previously
been shown to be equally efficacious as a larger stool sample (scoop),10 mailed to their
home. This kit includes a Fecal Collection Tube, a Feces Catcher, a Biohazard Bag,
Gloves, and multi-language instructions. To encourage participation and retention,
participants will be given a $40 gift certificate per stool sample with up to $200 total
compensation. Participants will mail stool samples to the Scripps Biorepository and
processed for storage at -80 degrees C. Once all samples are collected, they will be sent
to the Scripps Genomics Core for DNA extraction and 16S sequencing. Sequencing data
analysis by the CCBB will include taxonomic classification, abundance tables, diversity
analysis (alpha and beta indices), and principal component analysis (PCA) plots. Subset
analyses will compare participants with high/low fiber consumption, high/low caloric
intake, overweight/not overweight by BMI, and cancer-directed treatment (chemotherapy
alone or with immunotherapy).
Survey data will be imported into GraphPad Prism for visualization and analyses. For each
survey item collected at all 5 time points, a mixed effects model will be used where the
survey item result is the dependent variable, group (control or nutritional intervention)
and time point are fixed effects, and participant is treated as a random effect. The
mixed effects model uses restricted maximum likelihood estimation to account for missing
values. Residuals will be examined to ensure approximation of normality is met. P-values
will be reported for each fixed effect (group and time) and the interaction between these
effects, reported as time x group.
For TME analysis, up to 3 participants with high-fiber dietary intake who experience pCR
and 3 participants with residual disease (i.e. up to 6 total) will be selected based on
retrospective chart review, and biopsy samples pre- and post-treatment will be identified
through the Department of Pathology. Samples will be further processed and mounted onto
slides, each with 1 participant with matched pre- and post-neoadjuvant treatment samples
per slide for GeoMx spatial transcriptional profiling of 96 regions of interest (ROIs)
through the Scripps Genomics Core. The CCBB will perform statistical analysis to identify
signaling pathways and immune cell composition in TNBC.
At the end of the study, participants will be offered participation in a one-on-one
session via video conferencing platform (such as Zoom) to provide an opportunity for
participants to share in their own words their experiences in the study and in using the
survey app. Specifically, participants will be asked to discuss the utility of
educational materials provided, ease of navigating the study app and participating in the
study, and other feedback that will help medical oncologists and dietitians continuously
improve patients' experience during neoadjuvant treatment. Participants who uninstall the
CareEvolution app or have not engaged with the app for over 60 days will be disenrolled
from the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Diagnosis of early-stage triple-negative breast cancer, not on neoadjuvant systemic
therapy at the time of enrollment.
- Age greater than or equal to 18 years and less than 100 years
- English proficiency at or above 8th grade level
- Expected survival greater than or equal to 12 months
Exclusion Criteria:
- Prebiotic and/or probiotic use prior to and during the study
Gender:
All
Minimum age:
18 Years
Maximum age:
100 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Scripps Clinic
Address:
City:
La Jolla
Zip:
92037
Country:
United States
Contact:
Last name:
Lee Hong, MD, PhD
Phone:
858-554-8788
Email:
hong.lee@scrippshealth.org
Contact backup:
Last name:
Thomas Buchholz, MD
Email:
buchholz.thomas@scrippshealth.org
Investigator:
Last name:
Lee Hong, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Jacob New, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Gagandeep Kaur, DO
Email:
Sub-Investigator
Investigator:
Last name:
Laura Nicholson, MD, PhD
Email:
Sub-Investigator
Start date:
September 30, 2024
Completion date:
June 30, 2026
Lead sponsor:
Agency:
Scripps Health
Agency class:
Other
Collaborator:
Agency:
San Diego State University
Agency class:
Other
Collaborator:
Agency:
The Scripps Research Institute
Agency class:
Other
Source:
Scripps Health
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06610097
