Breast CancerPhase 2NCT05090358
Preventing High Blood Sugar in People Being Treated for Metastatic Breast Cancer
A Phase 2 study testing Ketogenic Diet, Low Carbohydrate Diet and Alpelisib in people with Breast Cancer and Breast Cancer Stage IV, run by Memorial Sloan Kettering Cancer Center at 9 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Breast Cancer Stage IV, Metastatic Breast Cancer
- What is being tested?
- Ketogenic Diet, Low Carbohydrate Diet and Alpelisib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 9 sitesUnited States
- Study dates
- 8 Oct 2021to 8 Oct 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Ohio State University (Data Collection & Data Analysis)
Columbus, Ohio, 43210
Memorial Sloan Kettering Suffolk - Commack (Limited protocol activity)
Commack, New York, 11725
Memorial Sloan Kettering Westchester (All protocol Activities)
East White Plains, New York, 10604
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical College (Data Collection & Data Analysis)
New York, New York, 10065
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
About this study
Official title: Targeting Insulin Feedback to Enhance Alpelisib (TIFA): A Phase 2 Randomized Control Trial in Metastatic PIK3CA-mutant Hormone-Receptor Positive Breast Cancer
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.
- Being tested
- Ketogenic Diet, Low Carbohydrate Diet, Alpelisib, Fulvestrant, Canagliflozin
- 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
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic DietDietary 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 DietDietary 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.
AlpelisibDrug
Also called Piqray
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.
FulvestrantDrug
Also called Faslodex
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.
CanagliflozinDrug
Also called Invokana
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: Drug: Alpelisib; Drug: Fulvestrant; Drug: Canagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start8 Oct 2021
- Primary completion8 Oct 2027 (estimated)
- Study completion8 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- New York University
- Responsible party
- Sponsor
- Investigators
- Sherry Shen, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05090358
- Sponsor's protocol ID
- 21-123
- Status last verified
- Aug 2026
- First submitted
- 12 Oct 2021
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Insulin Feedback to Enhance Alpelisib (TIFA): A Phase 2 Randomized Control Trial in Metastatic PIK3CA-mutant Hormone-Receptor Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT05090358
- Acronym / sponsor ID
- 21-123
- Keywords
- breast cancer, Metastatic Breast Cancer, breast cancer stage IV, PIK3CA-mutant, HR-Positive Breast Cancer, ketogenic diet, canagliflozin, 21-123
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- New York University
- Study start
- 8 Oct 2021 (actual)
- Primary completion
- 8 Oct 2027 (estimated)
- Study completion
- 8 Oct 2027 (estimated)
- First posted
- 22 Oct 2021 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ketogenic Diet | Experimental | Dietary Supplement: Ketogenic Diet, Drug: Alpelisib, Drug: Fulvestrant, Drug: CanagliflozinPostmenopausal 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 Diet | Experimental | Dietary Supplement: Low Carbohydrate Diet, Drug: Alpelisib, Drug: Fulvestrant, Drug: CanagliflozinPostmenopausal 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 Therapy | Experimental | Drug: Alpelisib, Drug: Fulvestrant, Drug: CanagliflozinPostmenopausal 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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
- 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
Key exclusion criteria (12 listed)
- 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.
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 |
|---|---|---|
| Ketogenic DietProperly 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. | Dietary supplement | Ketogenic Diet |
| Low Carbohydrate DietProperly 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. | Dietary supplement | Low Carbohydrate Diet |
| AlpelisibAlso: PiqrayThe 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. | Drug | Ketogenic Diet, Low Carbohydrate Diet, SGLT2i Therapy |
| FulvestrantAlso: FaslodexThe 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. | Drug | Ketogenic Diet, Low Carbohydrate Diet, SGLT2i Therapy |
| CanagliflozinAlso: InvokanaCanagliflozin 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. | Drug | Ketogenic Diet, Low Carbohydrate Diet, SGLT2i Therapy |
Primary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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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.
Sherry Shen, MD principal investigator
Memorial Sloan Kettering Cancer Center
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketogenic Diet, Low Carbohydrate Diet and Alpelisib in people with Breast Cancer and Breast Cancer Stage IV, run by Memorial Sloan Kettering Cancer Center at 9 sites 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 30 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Hyperglycemia-free rate for participants (time frame: 12 weeks). 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 11 Aug 2026.