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Preventing High Blood Sugar in People Being Treated for Metastatic 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: NCT05090358
Recruitment Status : Recruiting
First Posted : October 22, 2021
Last Update Posted : September 16, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Breast Cancer Stage IV Metastatic Breast Cancer Dietary Supplement: Ketogenic Diet Dietary Supplement: Low Carbohydrate Diet Drug: Alpelisib Drug: Fulvestrant Drug: Canagliflozin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Targeting Insulin Feedback to Enhance Alpelisib (TIFA): A Phase 2 Randomized Control Trial in Metastatic PIK3CA-mutant Hormone-Receptor Positive Breast Cancer
Actual Study Start Date : October 8, 2021
Estimated Primary Completion Date : October 8, 2024
Estimated Study Completion Date : October 8, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketogenic Diet
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
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.

Drug: Alpelisib
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.
Other Name: Piqray

Drug: Fulvestrant

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.

Other Name: Faslodex

Drug: Canagliflozin
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.
Other Name: Invokana

Experimental: Low Carbohydrate Diet
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
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.

Drug: Alpelisib
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.
Other Name: Piqray

Drug: Fulvestrant

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.

Other Name: Faslodex

Drug: Canagliflozin
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.
Other Name: Invokana

Experimental: SGLT2i Therapy
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
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.
Other Name: Piqray

Drug: Fulvestrant

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.

Other Name: Faslodex

Drug: Canagliflozin
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.
Other Name: Invokana




Primary Outcome Measures :
  1. Hyperglycemia-free rate for participants [ Time Frame: 12 weeks ]
    To determine the grade 3/4 hyperglycemia-free rate at 12 weeks, as assessed by the NCI CTCAE v5.0



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone and estradiol levels in the postmenopausal range without an alternative cause.

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

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): NCT05090358


Contacts
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Contact: Neil Iyengar, MD 646-888-4714 iyengarn@mskcc.org
Contact: Komal Jhaveri, MD 646-888-5145 jhaverik@mskcc.org

Locations
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United States, New Jersey
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Neil Iyengar, MD    646-888-8103      
Memorial Sloan Kettering Monmouth (Limited Protocol Activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Neil Iyengar, MD    646-888-4714      
Memorial Sloan Kettering Bergen (Limited Protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Neil Iyengar, MD    646-888-4714      
United States, New York
Memorial Sloan Kettering Suffolk - Commack (Limited protocol activity) Recruiting
Commack, New York, United States, 11725
Contact: Neil Iyengar, MD    646-888-4714      
Memorial Sloan Kettering Westchester (All protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Neil Iyengar, MD    646-888-4714      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Neil Iyengar, MD    646-888-4714      
Weill Cornell Medical College (Data Collection & Data Analysis) Not yet recruiting
New York, New York, United States, 10065
Contact: Eleni Andreopoulou, MD    646-962-9888      
Memorial Sloan Kettering Nassau (Limited Protocol Activities) Recruiting
Uniondale, New York, United States, 11553
Contact: Neil Iyengar, MD    646-888-4714      
United States, Ohio
Ohio State University (Data Collection & Data Analysis) Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Sagar Sardesai, MD    614-293-8000      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Neil Iyengar, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT05090358    
Other Study ID Numbers: 21-123
First Posted: October 22, 2021    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Canagliflozin
Fulvestrant
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents