TNBC Gut Microbiota During Neoadjuvant Treatment

NCT ID: NCT06610097

Last Updated: 2025-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-07

Study Completion Date

2026-06-30

Brief Summary

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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

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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.

Conditions

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Breast Cancer Triple Negative Breast Cancer Early Stage Triple-Negative Breast Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Educational Handout

Participants will receive usual standard of care for early-stage triple negative breast cancer and an educational handout on increasing dietary fiber.

Group Type NO_INTERVENTION

No interventions assigned to this group

High Fiber Dietary Counseling

Participants will receive usual standard of care for early-stage triple negative breast cancer and personalized nutritional counseling (initial 1 hour session with up to 2 30-minute follow-up sessions) on how to increase dietary fiber.

Group Type EXPERIMENTAL

Nutritional Counseling

Intervention Type OTHER

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.

Interventions

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Nutritional Counseling

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.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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San Diego State University

OTHER

Sponsor Role collaborator

The Scripps Research Institute

OTHER

Sponsor Role collaborator

Scripps Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lee Hong, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Scripps Clinic

Locations

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Scripps Clinic

La Jolla, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lee Hong, MD, PhD

Role: CONTACT

858-610-1321

Thomas Buchholz, MD

Role: CONTACT

858-678-7190

Facility Contacts

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Lee Hong, MD, PhD

Role: primary

858-554-8788

Thomas Buchholz, MD

Role: backup

References

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Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015 Aug 7;21(29):8787-803. doi: 10.3748/wjg.v21.i29.8787.

Reference Type BACKGROUND
PMID: 26269668 (View on PubMed)

Kok CR, Rose D, Hutkins R. Predicting Personalized Responses to Dietary Fiber Interventions: Opportunities for Modulation of the Gut Microbiome to Improve Health. Annu Rev Food Sci Technol. 2023 Mar 27;14:157-182. doi: 10.1146/annurev-food-060721-015516. Epub 2022 Nov 29.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 32833508 (View on PubMed)

Other Identifiers

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24-8410

Identifier Type: -

Identifier Source: org_study_id

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