Intermittent Fasting for the Improvement of Outcomes in Patients With Stage I-III Breast Cancer Receiving Chemotherapy Before Surgery

Study Overview
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Brief Summary
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This phase II trial studies whether intermittent fasting works to improve outcomes in patients with stage I-III breast cancer receiving chemotherapy before surgery (neoadjuvant) with a body mass index >= 25. Intermittent fasting has been shown to elicit similar metabolic changes as calorie restriction such as reduction in blood glucose levels, improved insulin sensitivity, and reduction of tumor cell growth. Intermittent fasting may improve outcomes in patients with breast cancer

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the proportion of patients that can adhere to intermittent fasting (14:10) in patients with HER2 negative and estrogen receptor (ER)/progesterone receptor (PR) < 10% breast cancer who receive neoadjuvant chemotherapy (NCT) for a new diagnosis of stage I-III breast cancer. SECONDARY OBJECTIVES: I. To evaluate the pathologic complete response (pCR) rate of intermittent fasting (14:10) in patients with HER2 negative and ER/PR < 10% breast cancer who receive neoadjuvant chemotherapy (NCT) for a new diagnosis of stage I-III breast cancer. II. To evaluate the effect of intermittent fasting in the prevention of weight gain, measured by body mass index (BMI) and waist circumference, in patients who are undergoing neoadjuvant chemotherapy. III. To evaluate the differences in the pCR rate among breast cancer patients within different race/ethnic groups, African American versus (vs.) Non-Hispanic White (AA vs NHW) and based on baseline social determinants of health when undergoing NCT. IV. To evaluate if study intervention acceptability, adherence, and engagement differ by race (AA vs NHW) and based on baseline social determinants of health. V. To evaluate if percent of patients with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 3 or 4 toxicities differ by race (AA vs NHW) and based on baseline social determinants of health. EXPLORATORY OBJECTIVES: I. To monitor changes in the following inflammatory markers in patients undergoing neoadjuvant chemotherapy with intermittent fasting: fasting glucose, hemoglobin A1c, insulin, leptin, adiponectin, free fatty acids and lipids. II. To measure changes in markers involved in metabolic and lipogenic signaling pathways, immune modulation, and autophagy in adipocytes, tumor cells, and surrounding immune cells by Reverse-Phase Protein microarrays (RPPA) analysis. OUTLINE: Patients undergo intermittent fasting involving 14 hours of fasting and 10 hours of eating for 4 months while undergoing standard of care neoadjuvant chemotherapy. After completion of study treatment, patients are followed up for 6 months.

Official Title
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Intermittent Fasting for Patients With HER2- Negative and ER/PR <10% Breast Cancer and Body Mass Index >= 25 Receiving Neoadjuvant Chemotherapy

Conditions
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Prognostic Stage IIIC Breast Cancer AJCC v8, Breast Ductal Carcinoma in Situ, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, HER2 Negative Breast Carcinoma, Hormone Receptor Positive Breast Carcinoma, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8

Intervention / Treatment
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* Other: Short-Term Fasting
* Other: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be >= 18 years of age at time of consent and must be able to understand and provide informed consent BMI >= 25 at time of enrollment Patient must have a recent diagnosis of histologically confirmed primary invasive breast carcinoma Multifocal or contralateral ductal carcinoma in situ (DCIS) or invasive breast cancers are allowed if the breast cancers meet the same eligibility criteria for ER/PR and HER2 Oligometastatic disease is allowed if treating physician recommends standard neoadjuvant chemotherapy Tumor status must be HER2 negative per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (determined by local testing) ER and PR expression must be < 10% cells positive by immunohistochemestry (IHC) test Patients must have clinical stage I-III (utilizing tumor, node, metastasis [TNM] criterion) at diagnosis Clinical T size must be >= 1.5 cm if there is no radiographic or clinical evidence of axillary lymph node involvement. Any size tumor is allowed if axillary lymph nodes appear to be involved Patient must be willing and able (have no contraindication) to receive recommended standard neoadjuvant therapy consisting of at least 16 weeks of planned neoadjuvant chemotherapy * Acceptable regimen includes doxorubicin and cytoxan followed by paclitaxel (AC-T). The schedule will be determined by treating physician. Carboplatin and pembrolizumab can also be added to the neoadjuvant chemotherapy regimen if determined to be appropriate by treating physician Patients must have organ and marrow function adequate for initiating neoadjuvant chemotherapy as determined by their treating physician Women of childbearing potential and sexually active males must use accepted and effective method(s) of contraception or abstain from sexual intercourse for the duration of their participation in the study and for 6 months after the last study intervention Exclusion Criteria: Clinical T4 and/or N3 disease, including inflammatory breast cancer Any prior treatment for the current breast cancer diagnosis, including surgery, chemotherapy, radiation, or experimental therapy Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive from the time of registration, while on study treatment, and until at least 6 months after the last study intervention Patients must not have impaired decision-making capacity Patients who are not English speaking as study staff is only able to provide the study intervention measurement tool and behavioral lifestyle coaching in English Patients that are > 2 weeks into starting neoadjuvant chemotherapy regimen

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (Intermittent Fasting)<br>Patients undergo intermittent fasting involving 14 hours of fasting and 10 hours of eating for approximately 4 months while undergoing standard of care neoadjuvant chemotherapy. | Other: Short-Term Fasting<br>* Undergo intermittent fasting<br>* Other names: Short-term Intermittent Fasting;Other: Chemotherapy<br>* Receive standard of care neoadjuvant chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who can adhere to to intermittent fasting > 80% of days |  | Through study participation; approximately 6 months |