Dietary Changes + Canagliflozin for Metastatic Breast Cancer

Not currently recruiting at 8 trial locations

Overseen By Neil Iyengar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Metformin

Must not be taking: Sulfonylureas, Meglitinides, SGLT2 inhibitors, Insulin

Disqualifiers: Type 1 diabetes, Uncontrolled type 2 diabetes, Vegetarian, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether a very low-carb diet (ketogenic diet), a low-carb diet, or the drug canagliflozin (used to control blood sugar) can help manage blood sugar and enhance cancer treatment effects in individuals with metastatic breast cancer. Participants will continue their usual cancer therapy with alpelisib and fulvestrant while trying one of these new approaches. The trial is suitable for postmenopausal women and men with a specific type of breast cancer (PIK3CA-mutant) who are experiencing recurrence or progression after endocrine-based therapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot be on anti-hyperglycemic medications other than metformin. If you are taking other diabetes medications, you may need to stop them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this trial have varying safety levels.

For the ketogenic diet, some studies suggest it can be safely followed by patients with advanced breast cancer and might help control body weight and blood sugar. However, other research indicates it could increase the risk of cancer spreading, resulting in mixed safety findings.

Studies have found that a low carbohydrate diet can be safely included in cancer treatment plans. This diet might even lower the risk of death from any cause in some breast cancer patients and is generally considered safe in cancer care.

Canagliflozin, a drug approved for type 2 diabetes, has been studied for its effects on breast cancer cells. It is generally seen as safe, with a well-known safety record in different patient groups. Overall, canagliflozin seems to be well-tolerated.

In summary, while there is some positive safety information for these treatments, it's important to consider the mixed findings, especially for the ketogenic diet. Always consult a healthcare provider to weigh the benefits and risks based on personal health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for metastatic breast cancer because they explore innovative dietary modifications alongside established drug therapies. Unlike the standard care options that focus solely on endocrine therapy and PI3K inhibition, this study incorporates a ketogenic or low carbohydrate diet, potentially enhancing the effectiveness of these treatments by altering metabolic pathways in cancer cells. Additionally, the inclusion of SGLT2 inhibitors introduces a novel angle by targeting glucose metabolism, which could offer a new mechanism to hinder cancer progression. These unique approaches aim to not only improve outcomes but also personalize treatment strategies for HR-positive, HER2-negative, PIK3CA mutant metastatic breast cancer.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

Research suggests that a ketogenic diet, which participants in one arm of this trial will follow, might aid cancer treatment when combined with medications like Fulvestrant. Some studies indicate it can lower insulin and blood sugar levels, potentially supporting cancer therapy. However, other studies suggest it could increase the risk of cancer spreading.

Participants in another arm of this trial will follow a low-carbohydrate diet. Strong evidence does not support the effectiveness of low-carbohydrate diets in treating cancer. Some studies show benefits in other areas, but not specifically for cancer.

Participants in a separate arm of this trial will receive Canagliflozin, a drug typically used for diabetes. It has shown potential in slowing the growth of breast cancer cells by blocking pathways that help cancer cells grow, offering hope for its use in cancer treatment. ^{1 4 5 6 7}

Who Is on the Research Team?

Neil Iyengar, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic HR-positive, HER2-negative breast cancer that has PIK3CA mutations. They must have had disease progression after endocrine therapy, be able to swallow pills, and follow a strict diet. Excluded are those underweight, with certain allergies or other cancers, uncontrolled diabetes, multiple chemotherapy treatments in the metastatic setting, or on specific diets.

Inclusion Criteria

My cancer has a PIK3CA mutation.

My breast cancer is HR-positive and HER2-negative.

My cancer can be measured by scans or I have at least one bone lesion.

Exclusion Criteria

You have an allergy or intolerance to eggs, gluten, nuts, or milk that would make it hard for you to follow the diet.

My diabetes is not under control (A1c is 8.0 or higher).

Currently participating in a study of an investigational agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a ketogenic diet, low carbohydrate diet, or SGLT2i therapy in combination with standard cancer treatment

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Canagliflozin
• Fulvestrant
• Ketogenic Diet
• Low Carbohydrate Diet

Trial Overview The study tests if a very low carbohydrate (ketogenic) diet, a low carbohydrate diet, or the drug canagliflozin prevents high blood sugar and improves effectiveness of standard treatment with alpelisib and fulvestrant in patients with specific breast cancer mutations.

How Is the Trial Designed?

Group I: SGLT2i Therapy Experimental Treatment 3 Interventions

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)

Group II: Low Carbohydrate Diet Experimental Treatment 4 Interventions

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)

Group III: Ketogenic Diet Experimental Treatment 4 Interventions

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)

Alpelisib is already approved in United States, European Union for the following indications:

Approved in United States as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Approved in European Union as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Alpelisib, when combined with fulvestrant, significantly improves progression-free survival (PFS) in postmenopausal women and men with hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer, showing a median PFS of 11 months compared to 5.7 months with placebo.

The treatment is specifically effective for patients with PIK3CA mutations, as no PFS benefit was observed in those without these mutations, highlighting the importance of genetic testing in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer. Narayan, P., Prowell, TM., Gao, JJ., et al.[2022]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

In a retrospective analysis of 33 patients with HR+, HER2- metastatic breast cancer, the combination of alpelisib and fulvestrant showed worse outcomes in heavily pretreated patients compared to those receiving it as a first-line treatment, with significant rates of disease progression and treatment discontinuation.

Adverse effects were common, with hyperglycemia (66.7%), rash (45.5%), and diarrhea (72.7%) leading to hospitalizations and pharmacological treatment, raising concerns about the tolerability of this regimen in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alpelisib in breast cancer: A real-world analysis. Miller, J., Armgardt, E., Svoboda, A.[2023]

Preliminary findings indicate that combining intermittent fasting or a fasting-mimicking diet with endocrine therapy may enhance the effectiveness of treatment for hormone receptor-positive breast cancer.

This combination approach could also help in reducing side effects associated with the endocrine therapy, suggesting a potential strategy for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting May Complement Endocrine Therapy. [2021]

In a study of 247 patients with metastatic hormone receptor-positive, PIK3CA-mutant breast cancer, 61.5% developed any-grade hyperglycemia after treatment with alpelisib, with a median onset time of just 16 days.

Patients receiving alpelisib as standard care experienced significantly higher rates of hyperglycemia compared to those in clinical trials, highlighting the importance of monitoring and optimizing glycemic status before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. Shen, S., Chen, Y., Carpio, A., et al.[2023]

Alpelisib is an effective treatment for advanced breast cancer in patients with specific genetic mutations, but it often causes hyperglycemia, which can lead to treatment complications.

In a case series of 3 patients, dietary changes and the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) were successful in managing hyperglycemia, suggesting potential strategies for improving patient outcomes during alpelisib therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Alpelisib-Induced Hyperglycemia with Very Low Carbohydrate Diets and Sodium-Glucose Co-Transporter 2 Inhibitors: A Case Series. Blow, T., Hyde, PN., Falcone, JN., et al.[2021]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05090358

Study Details | Preventing High Blood Sugar in People Being ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12135325/

The impact of sodium-glucose cotransporter-2 inhibitors on ... Canagliflozin, a widely studied SGLT-2 inhibitor, has demonstrated efficacy in suppressing breast cancer cell proliferation by inhibiting ...

3. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-025-02749-3

Unveiling the anticancer potential of SGLT-2 inhibitors [63] observed that canagliflozin use was associated with a reduction in HCC metastasis, further supporting its potential as a therapeutic agent ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0753332222010642

Canagliflozin interrupts mTOR-mediated inflammatory ... Herein, oral administration of canagliflozin (10 mg/kg, once daily for 3 weeks) to mammary cell cancer-bearing rats significantly decreased the mean body ...

5. withpower.com withpower.com/trial/phase-3-breast-neoplasms-9-2021-4c899

Dietary Changes + Canagliflozin for Metastatic Breast Cancer While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia ...

6. invokanahcp.com invokanahcp.com/safety-profiles/

Safety Profile | INVOKANA® (canagliflozin) HCP INVOKANA® safety was demonstrated across 3 patient populations with T2D ; Breast cancer · 0.16, 0.41, 2.59 (0.69, 9.76) ; Bladder cancer, 0.16, 0.17, 1.10 (0.45, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12330067/

Comparative risk of cancer associated with SGLT inhibitors ... This meta-analysis suggests that SGLT2 inhibitors are associated with a reduced overall risk of cancer compared to DPP-4 inhibitors in patients ...