Clinical Trials /

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

NCT03962647

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer
  • 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 IDs

  • ORG STUDY ID: VICC BRE 18108
  • SECONDARY ID: NCI-2019-03071
  • NCT ID: NCT03962647

Conditions

  • Estrogen Receptor-positive Breast Cancer

Interventions

DrugSynonymsArms
Letrozole2-Week Ketogenic Diet

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
2-Week Ketogenic DietExperimental2-Week Ketogenic Diet in Combination with Letrozole
  • Letrozole

Eligibility 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 reproducibly measurable by physical examination
                  and/or ultrasound and at least 1 cm 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 >= 40 IU/L and estradiol levels
                  <= 20 IU/L.

               -  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.

          -  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.

          -  Locally recurrent 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.

          -  Absence of a mammogram within three months of screening.

          -  Absence of a breast ultrasound within three months of screening.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Patients who complete the dietary intervention
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Measure enhanced inhibition of cancer cell proliferation
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Measured by Ki67
Measure:Reduction in measures of insulin/P13K pathway activation
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Marks of insulin receptor/PI3K pathway activation in tumors
Measure:Measure changes in body composition
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Waist circumference will be measured
Measure:Measure changes in body composition
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Weight will be checked
Measure:Measure changes in body composition
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Height will be checked
Measure:Measure changes in body composition
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Body mass index will be measured
Measure:Measure changes in insulin resistance
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Fasting glucose/insulin to measure HOMA-IR
Measure:Measure effectiveness in inducing a ketogenic state
Time Frame:After 2 weeks of a ketogenic diet
Safety Issue:
Description:Rate of ketones production

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Vanderbilt-Ingram Cancer Center

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