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

Phase 2
Active, not recruiting
Conditions
Breast Cancer
Breast Cancer Stage IV
Metastatic Breast Cancer
Interventions
Dietary Supplement: Low Carbohydrate Diet
Dietary Supplement: Ketogenic Diet
Drug: Alpelisib
Drug: Fulvestrant
Drug: Canagliflozin
Registration Number
NCT05090358
Lead Sponsor
Memorial Sloan Kettering Cancer Center
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
15
Inclusion Criteria
  • 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.
    • Life expectancy ≥6 months.
    • Adequate organ and marrow function as defined below:
  • Hemoglobin ≥9.0 g/dL (without blood transfusion within 7 days of laboratory test used to determine eligibility)

  • Absolute neutrophil count ≥1.5 × 109/L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility)

  • Platelet count ≥100 × 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility)

  • Total bilirubin (TB) ≤1.0 × institutional upper limit of normal (ULN; Patients with known Gilbert's disease who have TB ≤3 × ULN may be enrolled)

  • Aspartate transaminase/alanine transaminase ≤2.5 × ULN with normal alkaline phosphatase (≤5 × ULN for patients with liver metastases) OR ≤1.5 × ULN in conjunction with alkaline phosphatase >2.5 × ULN

  • Creatinine ≤1.5 mg/dL.

    • Fasting blood glucose ≤140 mg/dL and HbA1c <8% (both criteria have to be met) and not on anti-hyperglycemic medications other than metformin (i.e., metformin is allowable if fasting blood glucose and HbA1c parameters are met).
    • Able to swallow oral medication.
    • Willing to be randomized to any of the diet arms and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
    • Women must be of postmenopausal status. Postmenopausal status is defined by any one of the following criteria:
  • Prior bilateral oophorectomy or current ovarian suppression with a GnRH agonist

  • Age ≥60 years

  • Age <60 years and amenorrheic for at least 12 months (spontaneous cessation of menses for 12 consecutive months or more in the absence of chemotherapy

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Exclusion Criteria
  • 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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low Carbohydrate DietLow Carbohydrate DietPostmenopausal 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)
Ketogenic DietKetogenic DietPostmenopausal 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)
Ketogenic DietAlpelisibPostmenopausal 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)
Ketogenic DietFulvestrantPostmenopausal 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)
Ketogenic DietCanagliflozinPostmenopausal 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)
Low Carbohydrate DietFulvestrantPostmenopausal 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)
Low Carbohydrate DietAlpelisibPostmenopausal 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)
Low Carbohydrate DietCanagliflozinPostmenopausal 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)
SGLT2i TherapyFulvestrantPostmenopausal 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)
SGLT2i TherapyAlpelisibPostmenopausal 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)
SGLT2i TherapyCanagliflozinPostmenopausal 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)
Primary Outcome Measures
NameTimeMethod
Hyperglycemia-free rate for participants12 weeks

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

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (9)

Ohio State University (Data Collection & Data Analysis)

🇺🇸

Columbus, Ohio, United States

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

🇺🇸

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

🇺🇸

Middletown, New Jersey, United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

🇺🇸

Uniondale, New York, United States

Memorial Sloan Kettering Suffolk - Commack (Limited protocol activity)

🇺🇸

Commack, New York, United States

Memorial Sloan Kettering Westchester (All protocol Activities)

🇺🇸

Harrison, New York, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

🇺🇸

Montvale, New Jersey, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Weill Cornell Medical College (Data Collection & Data Analysis)

🇺🇸

New York, New York, United States

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