A 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer

NCT03962647 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: VICC BRE 18108NCI-2019-03071
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a neoadjuvant study to determine the feasibility and tolerability of 2 weeks of a very low carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+disease.

Conditions

Estrogen Receptor-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Patients who complete the dietary intervention

  The number of patients who complete the dietary intervention, as well as the reasons for early discontinuation and any adverse events will be reported. The number of of cases where pre- and post-treatment samples could be obtained and successfully analyzed for Ki67 and insulin signaling will also be reported.

  After 2 weeks of a ketogenic diet

Secondary Outcomes (7)

• Measure enhanced inhibition of cancer cell proliferation

  After 2 weeks of a ketogenic diet

• Reduction in measures of insulin/P13K pathway activation

  After 2 weeks of a ketogenic diet

• Measure changes in body composition

  After 2 weeks of a ketogenic diet

• Measure changes in body composition

  After 2 weeks of a ketogenic diet

• Measure changes in body composition

  After 2 weeks of a ketogenic diet

Study Arms (2)

2-Week Ketogenic Diet

EXPERIMENTAL

2-Week Ketogenic Diet in Combination with Letrozole

Dietary Supplement: 2-Week Ketogenic Diet; Drug: Letrozole

Letrozole Control

ACTIVE COMPARATOR

Drug: Letrozole

Interventions

2-Week Ketogenic Diet DIETARY_SUPPLEMENT

2-Week Ketogenic Diet in Combination with Letrozole

2-Week Ketogenic Diet

Letrozole DRUG

2.5 mg taken once daily by mouth

2-Week Ketogenic Diet; Letrozole Control

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must provide written informed consent.
• Patients must have histologically confirmed primary invasive mammary carcinoma
• The tumor must be estrogen receptor positive
• The tumor must be HER2 negative (negative IHC or FISH)
• The primary tumor size must be at least 2 mm in size.
• Patients must be post-menopausal defined by any of the following:
• Subjects at least 55 years of age.
• Subjects younger than 55 years of age and amenorrheic for at least 12 months or serum follicle-stimulating hormone (FSH) levels and estradiol levels in the post-menopausal range by local lab criteria
• Subjects with history of bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months.
• Patients must have clinical stage I, II, or III invasive mammary carcinoma planning to undergo surgical treatment with either segmental resection or total mastectomy.
• Patients must have BMI \>= 30.
• A core biopsy from the time of diagnosis must be available.
• Mammogram or ultrasound required prior to screening
• Patients must have adequate organ function based on the following laboratory parameters:
• Serum creatinine \<= 1.5x ULN

You may not qualify if:

• Patients with locally advanced disease who are candidates for other preoperative (chemo)therapy at the time of initial evaluation. This includes patients with inflammatory breast cancer.
• Evidence of distant metastatic disease (stage IV).
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
• Serious medical illness that in the judgment of the treating physician would preclude the use of a ketogenic diet.
• Severe uncontrolled malabsorption condition or disease (e.g. grade II/III diarrhea, severe malnutrition, short gut syndrome).
• Diabetes mellitus requiring insulin therapy.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Participation in any other neoadjuvant therapeutic clinical trial.
• Concurrent anti-cancer therapy other than endocrine therapy (e.g. chemotherapy, radiotherapy, immunotherapy, or any other biologic therapy).
• Concurrent treatment with an investigational agent.
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first day of dietary intervention.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

Diet, Ketogenic; Letrozole

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Brent Rexer, MD, PhD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 24, 2019
• Study Start: July 8, 2019
• Primary Completion: March 7, 2024
• Study Completion: July 14, 2024
• Last Updated: April 30, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)