Alpelisib + Endocrine Therapy for Breast Cancer

Recruiting at 3 trial locations

Overseen By Milena Petkov

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amanda Parkes

Must be taking: Alpelisib, Fulvestrant, Aromatase inhibitors

Must not be taking: Investigational drugs, Steroids

Disqualifiers: Chemotherapy, Active infection, Diabetes, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 months

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of alpelisib (Piqray) combined with ongoing endocrine therapy (either Fulvestrant or an Aromatase Inhibitor) for individuals with advanced breast cancer. It targets patients with HER2 negative breast cancer who have a specific PIK3CA gene mutation and have previously tried at least one hormone therapy. This trial may suit those with metastatic or hard-to-treat breast cancer that has spread or cannot be surgically removed. Participants will continue their current hormone therapy while taking alpelisib until their cancer progresses or side effects become too severe. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to continue using either Fulvestrant or an Aromatase Inhibitor as part of the treatment. The protocol does not specify if you need to stop other medications, so it's best to discuss your current medications with the trial team.

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

Research shows that alpelisib, when combined with fulvestrant or an aromatase inhibitor, is generally well-tolerated by patients with advanced breast cancer. In earlier studies, some patients taking alpelisib experienced common side effects like high blood sugar and diarrhea, but healthcare providers usually managed these effectively.

Alpelisib targets a specific gene mutation found in many breast cancers, enhancing treatment effectiveness. This treatment has been tested in other studies for similar conditions, providing some confidence in its safety. While side effects may occur, they typically do not outweigh the potential benefits. Patients should consult their doctors to understand how this treatment may affect them personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Alpelisib is unique because it specifically targets the PI3K pathway, which is often mutated in certain breast cancers, offering a more tailored approach compared to traditional endocrine therapies. While most standard treatments like aromatase inhibitors and Fulvestrant focus on blocking estrogen to slow tumor growth, Alpelisib directly inhibits a key protein involved in cancer cell survival and proliferation. Researchers are excited about Alpelisib because it offers a potential new mechanism of action that may enhance the effectiveness of existing therapies, especially for patients with specific genetic profiles.

What evidence suggests that Alpelisib combined with endocrine therapy could be an effective treatment for breast cancer?

Research has shown that alpelisib effectively treats breast cancer with a specific PIK3CA mutation. In this trial, participants will receive alpelisib combined with either an aromatase inhibitor or fulvestrant. Studies indicate that combining alpelisib with fulvestrant helps slow disease progression. One study found that this combination significantly improved progression-free survival, allowing patients to live longer without their cancer worsening. Additionally, real-world data supports alpelisib's effectiveness in patients who have already tried other treatments, making it a promising option for this type of breast cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Marina N. Sharifi

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adults with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer that has progressed after endocrine therapy. Participants must have an ECOG Performance Status of 0-2 and adequate organ function. Men and premenopausal women must agree to contraception. Exclusions include prior chemotherapy for advanced disease, other malignancies, CNS metastases causing symptoms, uncontrolled diseases or infections.

Inclusion Criteria

I agree to use effective birth control or abstain from sex during and 3 months after the study.

I am a man, or I am a woman who is postmenopausal or have been made postmenopausal.

I have been mostly active and able to care for myself in the last 28 days.

Exclusion Criteria

I have had serious heart issues or very high blood pressure in the last 6 months.

I have been treated with PI3K, mTOR, or AKT inhibitors for cancer that has spread.

I have received chemotherapy for my advanced or metastatic disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alpelisib daily in combination with continued use of either Fulvestrant or Aromatase Inhibitor until disease progression or unacceptable toxicity

Up to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 months

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Aromatase inhibitor
• Fulvestrant

Trial Overview The study tests alpelisib in combination with ongoing endocrine therapy (Fulvestrant or Aromatase Inhibitor) in patients whose breast cancer has worsened on just endocrine therapy. It's a multi-phase trial including screening, treatment until disease progression/toxicity, and post-treatment follow-up to assess safety and effectiveness.

How Is the Trial Designed?

Group I: Alpelisib + Aromatase Inhibitor or Fulvestrant Experimental Treatment 3 Interventions

Subjects will be treated with Alpelisib in combination with either an Aromatase Inhibitor or Fulvestrant per Standard of Care

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?

Amanda Parkes

Lead Sponsor

Trials

1

Recruited

40+

Marina N Sharifi

Lead Sponsor

Trials

1

Recruited

40+

Kari Wisinski

Lead Sponsor

Trials

3

Recruited

120+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

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 phase Ib study involving 26 patients with metastatic ER+ breast cancer, the combination of alpelisib and letrozole was found to be safe, with a maximum-tolerated dose of 300 mg/d and manageable side effects like hyperglycemia and fatigue.

The treatment showed a clinical benefit rate of 35%, particularly benefiting patients with PIK3CA mutations, where 44% experienced a lack of disease progression for at least 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer. Mayer, IA., Abramson, VG., Formisano, L., et al.[2022]

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 the phase III SOLAR-1 trial involving 571 patients, alpelisib combined with fulvestrant showed significant efficacy in treating PIK3CA-mutated advanced breast cancer, with a median progression-free survival of 12.5 months at higher dose intensities compared to 5.8 months with placebo.

Common adverse events included hyperglycemia and rash, which were effectively managed through early identification and preventive measures, leading to reduced severity and lower treatment discontinuation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Rugo, HS., André, F., Yamashita, T., et al.[2022]

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]

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]

In a study of 51 older breast cancer patients (median age 71), alpelisib was associated with significant adverse events, particularly hyperglycemia, which affected 37 patients and led to hospitalizations for 5.

Despite the adverse effects, there is potential for older patients to benefit from alpelisib if the management of these side effects, especially hyperglycemia, can be improved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observations with alpelisib in older patients (≥ 65 year of age) with breast cancer in a non-clinical trial setting. Almodallal, Y., Le-Rademacher, JG., Cook, KD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9631302/

Real world outcomes with alpelisib in metastatic hormone ... Alpelisib targets PIK3CA gene mutation which is identified in up to 40% of HR-positive HER2-negative primary and metastatic breast cancer (2). It has received ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13058

metastatic breast cancer in real-world clinical practice. The results of using alpelisib with fulvestrant confirm its effectiveness in real-world clinical practice in patients with pre-treated HR+HER2- negative ...

3. piqray-hcp.com piqray-hcp.com/metastatic-breast-cancer/efficacy/efficacy-results

Efficacy Results | PIQRAY® (alpelisib) tablets View the results of the SOLAR-1 clinical trial for PIQRAY, including progression-free survival and overall response. See full Prescribing & Safety Info.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1813904

Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive ... In a phase 1b trial, alpelisib plus fulvestrant led to a complete or partial response in 29% of patients with heavily pretreated PIK3CA-altered, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33246021/

final overall survival results from SOLAR-1 The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03056755

NCT03056755 | Study Assessing the Efficacy and Safety of ... Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2 ...