Estrogen Receptor-positive Breast CancerEarly Phase 1NCT03962647
A 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer
A Early Phase 1 study testing 2-Week Ketogenic Diet and Letrozole in people with Estrogen Receptor-positive Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Estrogen Receptor-positive Breast Cancer
- What is being tested?
- 2-Week Ketogenic Diet and Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jul 2019to 14 Jul 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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)
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
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
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.
Read the 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.
- Conditions
- Estrogen Receptor-positive Breast Cancer
- Being tested
- 2-Week Ketogenic Diet, Letrozole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2-Week Ketogenic DietDietary supplement
2-Week Ketogenic Diet in Combination with Letrozole
LetrozoleDrug
2.5 mg taken once daily by mouth
| Study group | Role | What they receive |
|---|---|---|
| 2-Week Ketogenic Diet | Experimental | 2-Week Ketogenic Diet in Combination with Letrozole Receives: Dietary Supplement: 2-Week Ketogenic Diet; Drug: Letrozole |
| Letrozole Control | Active comparator | Not described Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 2 weeks of a ketogenic diet
Secondary outcomes (7)
Measure enhanced inhibition of cancer cell proliferation
Measured by Ki67
Measured: After 2 weeks of a ketogenic diet
Reduction in measures of insulin/P13K pathway activation
Marks of insulin receptor/PI3K pathway activation in tumors
Measured: After 2 weeks of a ketogenic diet
Measure changes in body composition
Waist circumference will be measured
Measured: After 2 weeks of a ketogenic diet
Measure changes in body composition
Weight will be checked
Measured: After 2 weeks of a ketogenic diet
Measure changes in body composition
Height will be checked
Measured: After 2 weeks of a ketogenic diet
Measure changes in body composition
Body mass index will be measured
Measured: After 2 weeks of a ketogenic diet
Measure changes in insulin resistance
Fasting glucose/insulin to measure HOMA-IR
Measured: After 2 weeks of a ketogenic diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start8 Jul 2019
- Primary completion7 Mar 2024
- Study completion14 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Estrogen Receptor-positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brent Rexer, Vanderbilt-Ingram Cancer Center
- Investigators
- Brent Rexer, MD, PhD, Principal investigator, Vanderbilt Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962647
- Sponsor's protocol ID
- VICC BRE 18108
- Other IDs
- NCI-2019-03071
- Status last verified
- Sep 2025
- First submitted
- 21 May 2019
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03962647
- Acronym / sponsor ID
- VICC BRE 18108
- Conditions
- Estrogen Receptor-positive Breast Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Study start
- 8 Jul 2019 (actual)
- Primary completion
- 7 Mar 2024 (actual)
- Study completion
- 14 Jul 2024 (actual)
- First posted
- 24 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2-Week Ketogenic Diet | Experimental | Dietary Supplement: 2-Week Ketogenic Diet, Drug: Letrozole2-Week Ketogenic Diet in Combination with Letrozole |
| Letrozole Control | Active comparator | Drug: Letrozole |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- All participants must provide written informed consent.
- Patients must have histologically confirmed primary invasive mammary carcinoma
- Patients must be post-menopausal defined by any of the following:
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2-Week Ketogenic Diet2-Week Ketogenic Diet in Combination with Letrozole | Dietary supplement | 2-Week Ketogenic Diet |
| Letrozole2.5 mg taken once daily by mouth | Drug | 2-Week Ketogenic Diet, Letrozole Control |
Primary outcome
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.
7 secondary outcomes
Measure enhanced inhibition of cancer cell proliferation
Time frame: After 2 weeks of a ketogenic diet
Reduction in measures of insulin/P13K pathway activation
Time frame: After 2 weeks of a ketogenic diet
Measure changes in body composition
Time frame: After 2 weeks of a ketogenic diet
Measure changes in body composition
Time frame: After 2 weeks of a ketogenic diet
Measure changes in body composition
Time frame: After 2 weeks of a ketogenic diet
Measure changes in body composition
Time frame: After 2 weeks of a ketogenic diet
Measure changes in insulin resistance
Time frame: After 2 weeks of a ketogenic diet
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brent Rexer, MD, PhD principal investigator
Vanderbilt Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 2-Week Ketogenic Diet and Letrozole in people with Estrogen Receptor-positive Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients who complete the dietary intervention (time frame: After 2 weeks of a ketogenic diet). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.