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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03962647
Recruitment Status : Recruiting
First Posted : May 24, 2019
Last Update Posted : September 21, 2021
Sponsor:
Information provided by (Responsible Party):
Brent Rexer, Vanderbilt-Ingram Cancer Center

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.

Condition or disease Intervention/treatment Phase
Estrogen Receptor-positive Breast Cancer Dietary Supplement: 2-Week Ketogenic Diet Drug: Letrozole Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 8, 2019
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: 2-Week Ketogenic Diet
2-Week Ketogenic Diet in Combination with Letrozole
Dietary Supplement: 2-Week Ketogenic Diet
2-Week Ketogenic Diet in Combination with Letrozole

Drug: Letrozole
2.5 mg taken once daily by mouth

Active Comparator: Letrozole Control Drug: Letrozole
2.5 mg taken once daily by mouth




Primary Outcome Measures :
  1. Patients who complete the dietary intervention [ Time Frame: After 2 weeks of a ketogenic diet ]
    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 :
  1. Measure enhanced inhibition of cancer cell proliferation [ Time Frame: After 2 weeks of a ketogenic diet ]
    Measured by Ki67

  2. Reduction in measures of insulin/P13K pathway activation [ Time Frame: After 2 weeks of a ketogenic diet ]
    Marks of insulin receptor/PI3K pathway activation in tumors

  3. Measure changes in body composition [ Time Frame: After 2 weeks of a ketogenic diet ]
    Waist circumference will be measured

  4. Measure changes in body composition [ Time Frame: After 2 weeks of a ketogenic diet ]
    Weight will be checked

  5. Measure changes in body composition [ Time Frame: After 2 weeks of a ketogenic diet ]
    Height will be checked

  6. Measure changes in body composition [ Time Frame: After 2 weeks of a ketogenic diet ]
    Body mass index will be measured

  7. Measure changes in insulin resistance [ Time Frame: After 2 weeks of a ketogenic diet ]
    Fasting glucose/insulin to measure HOMA-IR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03962647


Contacts
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Contact: Vanderbilt-Ingram Service Information Program 800-811-8480 cip@vumc.org

Locations
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United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Vanderbilt-Ingram Service Information Program    800-811-8480    cip@vumc.org   
Principal Investigator: Brent Rexer, MD, PhD         
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
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Principal Investigator: Brent Rexer, MD, PhD Vanderbilt Medical Center
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Responsible Party: Brent Rexer, Sponsor Investigator, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT03962647    
Other Study ID Numbers: VICC BRE 18108
NCI-2019-03071 ( Registry Identifier: NCI, Clinical Trials Reporting Program )
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: September 21, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs