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

Estrogen Receptor-positive Breast Cancer Clinical Trial

Official title:

A Pilot and Feasibility Neoadjuvant Study of a 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03962647
• Other study ID #: VICC BRE 18108
• Secondary ID: NCI-2019-03071
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: July 8, 2019
• Est. completion date: May 2025

Study information

• Verified date: December 2023
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: May 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Estrogen Receptor-positive Breast Cancer

Intervention

Dietary Supplement:
• 2-Week Ketogenic Diet
2-Week Ketogenic Diet in Combination with Letrozole

Drug:
• Letrozole
2.5 mg taken once daily by mouth

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Measure enhanced inhibition of cancer cell proliferation	Measured by Ki67	After 2 weeks of a ketogenic diet
Secondary	Reduction in measures of insulin/P13K pathway activation	Marks of insulin receptor/PI3K pathway activation in tumors	After 2 weeks of a ketogenic diet
Secondary	Measure changes in body composition	Waist circumference will be measured	After 2 weeks of a ketogenic diet
Secondary	Measure changes in body composition	Weight will be checked	After 2 weeks of a ketogenic diet
Secondary	Measure changes in body composition	Height will be checked	After 2 weeks of a ketogenic diet
Secondary	Measure changes in body composition	Body mass index will be measured	After 2 weeks of a ketogenic diet
Secondary	Measure changes in insulin resistance	Fasting glucose/insulin to measure HOMA-IR	After 2 weeks of a ketogenic diet