Gut Microbiome, Adverse Effects, and Markers Through MEtabolic Reprogramming

NCT ID: NCT06536881

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-08
• Study Completion Date: 2029-05-31

Brief Summary

This research is being done to test the feasibility of 24-48 hours of water-only fasting to improve delivery of 4 cycles of chemotherapy in those receiving breast cancer treatment either before or after surgery.

Detailed Description

Breast cancer is the most common cancer diagnosed among women worldwide. Many women diagnosed with early stage breast cancer (ESBC) will receive systemic therapy consisting of cytotoxic chemotherapy. As therapy-related toxicities are the most common reason for non-completion or dose reduction of chemotherapy, new strategies are needed to mitigate adverse effects. Preclinical studies show that fasting can prevent toxic effects of oxidative stress and chemotherapy without causing chronic weight loss via modulation of key oncogenic pathways. A few studies in women with breast cancer have demonstrated that fasting around chemotherapy is safe and has the same or fewer expected toxicities, although the underlying biological mechanisms for these findings is unknown. A better understanding of the mechanistic underpinnings of fasting interventions can lead to future interventions to enhance tolerability of chemotherapy and ultimately, maintaining intended chemotherapy dosing and schedule.

The primary objective of this study is to determine the feasibility of water-only fasting during chemotherapy (standard of care Taxotere and Cyclophosphamide (TC) every 3 weeks for 4 cycles or dose dense doxorubicin and cyclophosphamide (ddAC) every 2 weeks for 4 cycles) in 30 patients with early stage breast cancer. Concomitant human epidermal growth factor 2 (HER2) therapy is allowed. The investigators designed a bed-to-bench feasibility study called the Gut microbiome, Adverse effects, and Markers through MEtabolic Reprogramming (GAMMER) study. Feasibility will be evaluated by the proportion of participants with self-reported adherence to the fasting regimen. The investigators will consider the fasting intervention to be feasible if there is evidence that at least 70% of patients (corresponding with 24 out of 30 patients) adhere to the intervention for at least 3 of 4 cycles of chemotherapy.

Prior to chemotherapy, patients will undergo a dose finding for fasting. A minimum of one successful 24 hour fast is required during this. A maximum of three trials is allowed. Participants have the option to progressively increase the fasting window by 12 hours each week as tolerated or to a maximum of 48 hours). Patients who are unable to adhere to at least a 24 hour fast during the dose finding phase will be replaced. Once patients have a fasting dose established, this will be the starting dose used for Cycle 1 of 4 of scheduled chemotherapy.

The investigators also aim to understand the impact of short-term fasting on quality of life, as well as key cytokines, metabolites and gut microbiome. Participants will complete patient reported outcomes (PROs) weekly. The investigators will collect fasting labs and research blood with each cycle of chemotherapy (4 instances). The investigators will also collect research bloods at baseline. The investigators will collect stool samples at baseline, and after fasting interventions for Cycle 1 and 3.

Through the proposed investigations the investigators will test the feasibility of a promising strategy to augment delivery of chemotherapy in a population at risk for toxicity for cancer therapy, and explore the mechanisms by which it may function. The long-term goals are to: enhance patient experience during chemotherapy, improve survival outcomes, and reduce disparities in survival between those who received recommended dose of chemotherapy versus those who require a dose reduction due to side effects. The study can potentially move the field forward by (a) identifying key cytokine, microbiome and metabolome changes associated with short-term fasting in ESBC and (b) improving survival outcomes in patients with ESBC.

Conditions

Breast Cancer; Early-stage Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Fasting prior to chemotherapy

Prior to chemotherapy administration, a trial of a 24-hour water-only fast will be conducted; at least 1 successful 24-hour fast is required to proceed with the fasting intervention during chemotherapy. A total of 3 trials is allowed (for a maximum of 48 hours fasting).

Group Type: EXPERIMENTAL

Fasting

Intervention Type: BEHAVIORAL

The dietician will review the patient's chemotherapy schedule, and confirm the fasting window (as windows may be 24, 26 or 48 hours; and chemotherapy start times can vary from patient to patient).

Interventions

Fasting

The dietician will review the patient's chemotherapy schedule, and confirm the fasting window (as windows may be 24, 26 or 48 hours; and chemotherapy start times can vary from patient to patient).

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Diagnosed with histologically-confirmed stage I-III invasive carcinoma of the breast
• Planning for standard neoadjuvant or adjuvant chemotherapy ddAC or TC for 4 cycles (concurrent anti-HER2 therapy is permitted)
• Provider physical exam within 4 weeks of consent
• Eastern Cooperative Oncology Group (ECOG) 0-1 (as per recent provider note or direct confirmation with provider)
• BMI ≥ 19.5 kg/m2 (as per most recent visit documented in medical record)
• Willingness to change diet, and provide fecal sample 3 times during study

Exclusion Criteria

• BMI <19.5 kg/m2
• Diabetes
• History of eating disorder
• Serious/uncontrolled medical condition (e.g. end stage renal disease on dialysis, cirrhosis, uncontrolled hypertension, seizure disorder, history of bariatric surgery)
• Pregnant or nursing
• Use of medications that must be taken with food: allopurinol, aspirin, amiodarone, baclofen, bromocriptine, carvedilol, carbamezpine, cimetidine, diclofenac, doxycycline, fenofibrate, fludrocortisone, glyburide, hydrocortisone, iron supplements, ketorolac, lithium, methylprednisolone, naproxen, niacin, potassium salts, prednisone, procainamide, sevelamer, sulfasalazine, trazodone, valproic acid

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The Commonwealth Fund

OTHER

Sponsor Role: collaborator

Maryland Cigarette Restitution Fund

OTHER_GOV

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Sheng, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer Sheng, MD

Role: CONTACT

jsheng7@jhmi.edu

202-537-4000

Facility Contacts

Azka Tariq

Role: primary

atariq6@jhmi.edu

202-660-5712

Aliya Lalji

Role: backup

alalji1@jhmi.edu

202-243-2294

Other Identifiers

IRB00390964

Identifier Type: OTHER

Identifier Source: secondary_id

J2362

Identifier Type: -

Identifier Source: org_study_id