Alpelisib + Enzalutamide for Breast Cancer

Overseen By Meghan S. Karuturi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: PI3K inhibitors, Anti-androgen therapies

Disqualifiers: Uncontrolled diabetes, Cardiac disease, Seizures, others

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

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

Compensation: Varies

Number of Visits: 5

Duration: 16 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are strong inhibitors or inducers of certain liver enzymes (CYP3A or CYP2C8) at least one week before starting the study. If you are on medications that prolong the QT interval, you may need to switch to a different medication before starting the trial. Please consult with the study team for specific guidance on your current medications.

What data supports the effectiveness of the drugs Alpelisib and Enzalutamide for breast cancer?

Alpelisib has shown effectiveness in treating hormone receptor-positive breast cancer with PIK3CA mutations, leading to its approval for this use. Enzalutamide has been effective in improving endocrine therapy for hormone receptor-positive breast cancer and has shown responses in advanced triple-negative breast cancer. ^{1 2 3 4 5}

Is the combination of Alpelisib and Enzalutamide safe for humans?

Alpelisib has been shown to cause high rates of side effects like high blood sugar, skin rash, and diarrhea, which sometimes required hospital treatment. Enzalutamide has been used in prostate cancer treatment, but specific safety data for its combination with Alpelisib in breast cancer is not detailed in the available research. ^{1 2 5 6 7}

How is the drug combination of Alpelisib and Enzalutamide unique for breast cancer treatment?

The combination of Alpelisib and Enzalutamide is unique because Alpelisib targets a specific mutation (PIK3CA) in hormone receptor-positive breast cancer, while Enzalutamide blocks the androgen receptor, which may help overcome resistance to traditional hormone therapies. This dual approach targets different pathways that contribute to cancer growth, offering a novel strategy for treating this type of breast cancer. ^{1 2 4 8 9}

What is the purpose of this trial?

This trial tests the combination of alpelisib and enzalutamide in patients with advanced breast cancer that has specific markers. The drugs work together to block cancer cell growth and reduce hormone levels, aiming to improve treatment outcomes. Alpelisib is a unique drug approved for the treatment of patients with estrogen receptor-positive metastatic breast cancer.

Research Team

Meghan Karuturi

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with metastatic breast cancer that's hormone-receptor positive or triple-negative, and not suitable for surgery/radiation. Participants must have stable health, meet specific blood/lab criteria, and not be pregnant or breastfeeding. They should agree to use effective contraception if of childbearing potential.

Inclusion Criteria

You have a certain type of breast cancer that is either hormone-receptor positive or triple-negative.

You meet specific requirements for blood cell counts, kidney function, liver function, and blood sugar levels.

If you have cancer in your brain or spinal cord, it must meet certain conditions, including waiting at least 4 weeks after previous treatment, not having cancer in the fluid around the brain, and having breast cancer that cannot be treated with surgery or radiation at the time of screening.

Exclusion Criteria

Female patients of childbearing potential are not willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study.

If you are a woman who could become pregnant, you must have a negative pregnancy test within a week before starting the study drug.

Patient has any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with patient's safety, provision of informed consent, or compliance with the study procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alpelisib and enzalutamide orally on days 1-28, with cycles repeating every 28 days

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Alpelisib
• Enzalutamide

Trial Overview The trial tests the combination of Alpelisib and Enzalutamide in patients with advanced breast cancer. It aims to find the best dose while assessing side effects. Alpelisib blocks enzymes needed for tumor growth; Enzalutamide lowers body's androgen to combat cancer cell growth.

Participant Groups

Group I: Treatment (alpelisib, enzalutamide) Experimental Treatment 2 Interventions

Patients receive alpelisib PO and enzalutamide PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Alpelisib (PIQRAY®) is the first PI3K inhibitor approved for treating hormone receptor-positive metastatic breast cancer with PIK3CA mutations, showing promising clinical results that support its use in overcoming endocrine resistance.

The review highlights the pharmacodynamic and pharmacokinetic properties of alpelisib, along with safety and efficacy data from the Phase III SOLAR-1 trial, which led to its FDA approval, indicating its potential as a tailored treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. Mavratzas, A., Marmé, F.[2021]

Alpelisib (Piqray™) is an oral PI3K inhibitor specifically targeting PI3Kα, showing efficacy in treating hormone receptor-positive, HER2-negative breast cancer in patients with a PIK3CA mutation.

The drug has been approved in the USA for use in combination with fulvestrant, marking a significant milestone in its development for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. Markham, A.[2020]

Alpelisib (Piqray) is effective for treating advanced or metastatic breast cancer that is HR-positive, HER2-negative, and has PIK3CA mutations, targeting specific genetic alterations to improve treatment outcomes.

Polatuzumab vedotin-piiq (Polivy) is used for diffuse large B-cell lymphoma, while eculizumab (Soliris) is indicated for neuromyelitis optica spectrum disorder, highlighting the development of targeted therapies for specific cancer types and autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

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]

In a study of 76 women with hormone receptor-positive, HER2-negative metastatic breast cancer, alpelisib combined with endocrine therapy demonstrated a median progression-free survival of 5.2 months, indicating its effectiveness in a real-world setting.

However, about 31.6% of patients had to permanently discontinue alpelisib due to adverse events, with hyperglycemia being the most common serious side effect, highlighting the need for careful monitoring of patients on this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience. Sarfraz, H., Bari, S., Whiting, J., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor-Positive Breast Cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

AR Inhibition Achieves Responses in AR+ Triple-Negative Breast Cancer. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alpelisib in breast cancer: A real-world analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Constitutively active androgen receptor supports the metastatic phenotype of endocrine-resistant hormone receptor-positive breast cancer. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience. [2023]