Preventing High Blood Sugar in People Being Treated for Metastatic Breast Cancer

NCT05090358 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-123
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study to find out whether a very low carbohydrate diet (ketogenic diet), a low carbohydrate diet, or the study drug canagliflozin can prevent high blood sugar and may improve the effectiveness of cancer therapy in people who are receiving standard treatment with alpelisib and fulvestrant for their metastatic PIK3CA-mutant breast cancer.

Conditions

Breast Cancer; Breast Cancer Stage IV; Metastatic Breast Cancer

Keywords

breast cancer; Metastatic Breast Cancer; breast cancer stage IV; PIK3CA-mutant; HR-Positive Breast Cancer; ketogenic diet; canagliflozin; 21-123; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Hyperglycemia-free rate for participants

  To determine the grade 3/4 hyperglycemia-free rate at 12 weeks, as assessed by the NCI CTCAE v5.0

  12 weeks

Study Arms (3)

Ketogenic Diet

EXPERIMENTAL

Postmenopausal women and men with histologically-confirmed, HR-positive, HER2-negative, PIK3CA mutant MBC who have received no more than 1 line of endocrine-based therapy in the metastatic setting will be eligible. Participants on this arm will partake in a ketogenic diet in combination with SOC endocrine therapy (fulvestrant) and PI3K inhibition (alpelisib)

Dietary Supplement: Ketogenic Diet; Drug: Alpelisib; Drug: Fulvestrant; Drug: Canagliflozin

Low Carbohydrate Diet

EXPERIMENTAL

Postmenopausal women and men with histologically-confirmed, HR-positive, HER2-negative, PIK3CA mutant MBC who have received no more than 1 line of endocrine-based therapy in the metastatic setting will be eligible. Participants on this arm will be assigned to Low Carbohydrate Diet/LCD therapy each in combination with SOC endocrine therapy (fulvestrant) and PI3K inhibition (alpelisib)

Dietary Supplement: Low Carbohydrate Diet; Drug: Alpelisib; Drug: Fulvestrant; Drug: Canagliflozin

SGLT2i Therapy

EXPERIMENTAL

Postmenopausal women and men with histologically-confirmed, HR-positive, HER2-negative, PIK3CA mutant MBC who have received no more than 1 line of endocrine-based therapy in the metastatic setting will be eligible. Participants on this arm will be assigned to SGLT2i therapy each in combination with SOC endocrine therapy (fulvestrant) and PI3K inhibition (alpelisib)

Drug: Alpelisib; Drug: Fulvestrant; Drug: Canagliflozin

Interventions

Ketogenic Diet DIETARY_SUPPLEMENT

Properly formulated meals will be provided to both diet groups for the first 12 weeks to facilitate compliance in women with metastatic breast cancer prescribed alpelisib. After 12 weeks, subjects on the two dietary arms will be given the option to cross-over to the other diet arm and continue the prescribed dietary formulation. The decision to cross over will be per patient preference.

Ketogenic Diet

Low Carbohydrate Diet DIETARY_SUPPLEMENT

Properly formulated meals will be provided to both diet groups for the first 12 weeks to facilitate compliance in women with metastatic breast cancer prescribed alpelisib. After 12 weeks, subjects on the two dietary arms will be given the option to cross-over to the other diet arm and continue the prescribed dietary formulation. The decision to cross over will be per patient preference.

Low Carbohydrate Diet

Alpelisib DRUG

The recommended dose of PIQRAY is 300 mg (two 150 mg film-coated tablets) taken orally, once daily, with food. Patients should take their dose of PIQRAY at approximately the same time each day.

Also known as: Piqray

Ketogenic Diet; Low Carbohydrate Diet; SGLT2i Therapy

Fulvestrant DRUG

The recommended dose is 500 mg to be administered intramuscularly into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter.

Also known as: Faslodex

Ketogenic Diet; Low Carbohydrate Diet; SGLT2i Therapy

Canagliflozin DRUG

Canagliflozin is an inhibitor of SGLT2, the transporter responsible for reabsorbing the majority of glucose filtered by the kidney. For the first week of canagliflozin dosing, the dose will be 100 mg. Starting week 2 and onward the dose will be 300 mg and supplied by the site.

Also known as: Invokana

Ketogenic Diet; Low Carbohydrate Diet; SGLT2i Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic HR-positive, HER2-negative breast cancer. HR positive is defined by ER status \>10% immunohistochemical (IHC) staining of any intensity. HER2 negativity is defined as the following as per the 2018 American Society of
• Clinical Oncology and College of American Pathologists guidelines:
• IHC score of 0 or 1+ or
• Single-probe average HER2 copy number of \<4 signals/cell or
• Dual-probe HER2/CEP17 ratio \<2 with an average HER2 copy number of \<4 signals/cell or
• IHC 0, 1+, or 2+ and dual-probe HER2/CEP17 ratio ≥2 with an average HER2 copy number of \<4 signals/cell or
• IHC 0 or 1+ and dual-probe HER2/CEP17 ratio \<2 with an average HER2 copy number of ≥6 signals/cell or
• IHC 0 or 1+ and dual-probe HER2/CEP17 ratio \<2 with an average HER2 copy number of ≥4 and \<6 signals/cell.
• Presence of one or more activating PIK3CA mutations in tumor tissue.
• Measurable or non-measurable disease per RECIST v1.1 OR at least one predominantly lytic bone lesion must be present.
• Written informed consent provided
• Female or male ≥18 years of age
• Adequate archived tumor tissue for the analysis of PIK3CA mutational status or evaluable circulating tumor DNA (ctDNA) for analysis of PIK3CA mutation status
• Recurrence or progression of disease during or after endocrine-based therapy
• Eastern Cooperative Oncology Group performance status of 0 or 1.

You may not qualify if:

• Multiple prior lines of chemotherapy in the metastatic setting (One line of chemotherapy is allowed. Also prior treatment with CDK4/6 inhibitors is allowed)
• Currently participating in a study of an investigational agent
• Current participation in a formalized weight loss program or currently consuming a ketogenic diet
• Body mass index \< 20 kg/m\^2
• Known hypersensitivity to alpelisib, fulvestrant, canagliflozin, or to any of the excipients of alpelisib or fulvestrant.
• Concurrent malignancy (basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone curative intent therapy are allowed)
• Type 1 diabetes mellitus
• Uncontrolled type 2 diabetes mellitus (hemoglobin A1c ≥8.0)
• Type 2 diabetes mellitus requiring treatment with a sulfonylurea, meglitinide, SGLT2 inhibitors or insulin.
• Vegetarian or vegan eating habits.
• Allergy or intolerance to egg, gluten, nut or milk protein that would interfere with adherence to diet.
• Individuals with impaired decision making capacity

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (9)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack (Limited protocol activity)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical College (Data Collection & Data Analysis)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Ohio State University (Data Collection & Data Analysis)

Columbus, Ohio, 43210, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Diet, Ketogenic; Diet, Carbohydrate-Restricted; Alpelisib; Fulvestrant; Canagliflozin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Sherry Shen, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: October 22, 2021
• Study Start: October 8, 2021
• Primary Completion (Estimated): October 8, 2026
• Study Completion (Estimated): October 8, 2026
• Last Updated: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (9)