A 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer
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.
- Estrogen Receptor-positive Breast Cancer
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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 - SGOT, SGPT <= 4x ULN (unless known steatohepatitis) - Serum albumin >= 2.0 g/dL - Total serum bilirubin <= 1.5x ULN (or <= 3x ULN if known Gilbert's syndrome)
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.
- Early Phase 1
- Study Type
- Intervention Model
- Single Group Assignment
- Primary Purpose
- None (Open Label)
2-Week Ketogenic Diet
|2-Week Ketogenic Diet in Combination with Letrozole||
- Vanderbilt-Ingram Cancer Center
Study ContactVanderbilt-Ingram Service Information Program
Primary Objective: • To evaluate the feasibility and tolerability of a 2 week ketogenic diet in combination with endocrine therapy prior to surgery for early stage ER+ breast cancer. Secondary Objectives - To determine whether endocrine therapy in combination with a dietary intervention to reduce insulin pathway signaling results in enhanced inhibition of cancer cell proliferation (measured byKi67) - To determine the effectiveness of 2 weeks of a ketogenic diet to reduce measures of insulin/PI3Kpathway activation in breast tumors - To measure changes in weight and body composition after 2 weeks of a ketogenic diet - To measure changes in insulin resistance after 2 weeks of a ketogenic diet - To measure the effectiveness of a ketogenic diet in combination with endocrine therapy to induce and maintain a ketogenic state. Outline: Participants will have baseline metabolic parameters measured and will begin a 2-week diet consisting of meal replacement shakes to induce a ketogenic state. Patients will also receive letrozole 2.5 mg daily. At the end of 2 weeks, metabolic parameters will again be measured and patients will proceed with surgical treatment of their breast cancer. A tumor biopsy from the surgical specimen will be obtained to measure cell proliferation compared with the pre-treatment diagnostic biopsy.