Active, not recruiting • Phase I • Stage I, II, III • ER positive • Post-Menopausal • Brain Metastases absent • Interventional

The following is imported from ClinicalTrials.gov:

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

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.

Description

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.

Study Design

Eligibility Criteria

Arms and Intervention

• 2-Week Ketogenic Diet

• Letrozole

Inclusion criteria

• 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)

Exclusion criteria

• 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.