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

• Status: Recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt-Ingram Cancer Center
• Treatments: Letrozole

Criteria

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.