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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and examine the side effects of two drugs, alpelisib (Piqray) and enzalutamide (Xtandi), for treating a specific type of breast cancer. The focus is on breast cancer that has spread and exhibits certain markers, such as androgen receptor and PTEN positivity. These drugs work together to inhibit cancer cell growth by blocking specific enzymes and reducing hormone levels. Suitable candidates have metastatic breast cancer that cannot be treated with surgery or radiation and possess specific tumor markers. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the combination of alpelisib and enzalutamide is being tested for safety in patients with certain types of breast cancer. Previous studies have provided useful information about how well patients handle this combination. Specifically, research on alpelisib has shown it works well for treating certain breast cancers with a specific mutation, leading to its approval for those cases.

While this combination is still in early testing for breast cancer, past studies found that patients generally handled the treatment well. However, like any new treatment, some side effects have been reported. It's important to talk with a healthcare provider about the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using alpelisib and enzalutamide for breast cancer because they target unique pathways that aren't the primary focus of current treatments. Alpelisib works by inhibiting the PI3K pathway, which is often overactive in cancer cells and drives their growth. Enzalutamide, on the other hand, is typically used for prostate cancer to block androgen receptors, but its application in breast cancer is novel, providing a new angle of attack. This combination could potentially offer new hope for patients, especially those whose cancer is resistant to standard therapies like hormone blockers or chemotherapy.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

This trial will evaluate the combination of alpelisib and enzalutamide for treating certain types of breast cancer. Studies have shown that alpelisib is particularly effective for hormone receptor-positive breast cancer with PIK3CA mutations. Research found that this drug combination helped 49% of patients, meaning their cancer either shrank, stopped growing, or remained stable. Enzalutamide lowers male hormones, which can help slow cancer growth. This combination targets specific parts of cancer cells, potentially stopping them from growing and spreading. ^{1 2 3 4 6}

Who Is on the Research Team?

Meghan Karuturi

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03207529

Study Details | NCT03207529 | Alpelisib and Enzalutamide ... Hormone therapy using enzalutamide may fight breast cancer by lowering the amount of androgen the body makes. Giving alpelisib and enzalutamide may work better ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705204/

Breast Cancer Treatment: To tARget or Not? That Is the Question This drug treatment was shown to achieve a CBR of 49%. This was measured by summing complete and partial responses as well as stable disease at or after 24 ...

3. withpower.com withpower.com/trial/phase-1-breast-neoplasms-5-2019-77aaf

Alpelisib + 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 ...

4. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/4693/738690/Abstract-4693-A-Phase-1b-study-of-BYL719-Alpelisib

Abstract 4693: A Phase 1b study of BYL719 (Alpelisib) in ... Methods: We conducted a phase 1b clinical trial of BYL719 in combination with enzalutamide for patients with AR-positive (defined as ≥ 1% of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0304383524006141

Combined inhibition of CDK4/6 and AKT is highly effective ... Currently, the PI3Kα inhibitor alpelisib and the AKT inhibitor capivasertib are approved for treatment of ER + breast cancers with PIK3CA ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03207529?term=AREA%5BBasicSearch%5D(Androgens%20AND%20PTEN)&rank=1

Alpelisib and Enzalutamide in Treating Patients With ... A type of intervention model describing a clinical trial in which two or more groups of participants receive different interventions. For example, a two-arm ...