Alpelisib + Fulvestrant for Breast Cancer

(EPIK-B5 Trial)

Recruiting at 77 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Fulvestrant, SERDs, PI3K inhibitors

Disqualifiers: Symptomatic visceral disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 1

Duration: Up to 60 months

211 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether a new drug combination of alpelisib and fulvestrant works better than just fulvestrant alone in men and postmenopausal women with a specific type of advanced breast cancer. Alpelisib targets cancer cell mutations, while fulvestrant blocks hormones that help the cancer grow.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have prior treatment with fulvestrant, oral SERDs, PI3K, mTOR, or AKT inhibitors.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have previously been treated with fulvestrant or certain other specific drugs, you may not be eligible to participate.

What safety data exists for Alpelisib + Fulvestrant in breast cancer treatment?

The combination of Alpelisib (Piqray) and Fulvestrant (Faslodex) has been studied for safety in treating HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer. The SOLAR-1 study, which led to FDA approval, reported common adverse reactions such as increased glucose, creatinine, diarrhea, rash, and nausea. Real-world analyses indicate high rates of hyperglycemia, rash, and diarrhea, with some cases requiring hospitalization and treatment. The safety profile necessitates careful patient selection and monitoring, especially regarding glycemic status. ^{1 2 3 4 5}

What safety information is available for the combination of Alpelisib and Fulvestrant in breast cancer treatment?

The combination of Alpelisib and Fulvestrant is generally safe but can cause side effects like high blood sugar, rash, and diarrhea, which sometimes require hospital treatment. It's important for patients to be monitored closely, especially for blood sugar levels. ^{1 2 3 4 5}

Is the drug Alpelisib + Fulvestrant a promising treatment for breast cancer?

Yes, the drug Alpelisib combined with Fulvestrant is promising for treating a specific type of breast cancer. It has shown to improve the time patients live without the cancer getting worse, especially in those with a certain gene mutation. This combination has been approved for use in the USA and Europe, indicating its effectiveness. ^{1 3 4 5 6}

How is the drug Alpelisib + Fulvestrant unique for breast cancer treatment?

Alpelisib + Fulvestrant is unique because it specifically targets PIK3CA-mutated, hormone receptor-positive, HER2-negative breast cancer, improving progression-free survival compared to fulvestrant alone. Alpelisib is the first PI3K inhibitor approved for this type of breast cancer, offering a novel approach for patients whose disease has progressed after other hormone therapies. ^{1 3 4 5 6}

What data supports the idea that Alpelisib + Fulvestrant for Breast Cancer is an effective drug?

The available research shows that Alpelisib combined with Fulvestrant is effective for treating a specific type of breast cancer that has a PIK3CA mutation. In a study called SOLAR-1, patients who took Alpelisib with Fulvestrant had their cancer stay under control for about 11 months on average, compared to only 5.7 months for those who took Fulvestrant with a placebo. This means the combination drug helped keep the cancer from getting worse for a longer time. Another study from France also showed that patients who had already tried other treatments still benefited from this combination, even though they had been heavily pre-treated. However, it's important to note that this drug can have side effects, like increased blood sugar levels, so patients need to be monitored carefully. ^{1 2 3 4 6}

What data supports the effectiveness of the drug combination Alpelisib and Fulvestrant for breast cancer?

Research shows that Alpelisib combined with Fulvestrant is effective for treating a specific type of advanced breast cancer with a PIK3CA mutation. In a study, patients taking this combination had a longer time before the cancer worsened compared to those taking Fulvestrant alone. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HR-positive, HER2-negative advanced breast cancer who have progressed after treatment with an AI and a CDK4/6 inhibitor. They must have at least one measurable lesion, a PIK3CA mutation, and if female, be postmenopausal. They can't join if they've had more than two systemic therapies in the metastatic setting or prior treatment with certain inhibitors.

Inclusion Criteria

My breast cancer is not HER2 positive.

I've had 2 or fewer treatments for my cancer, with only one being chemotherapy.

I have at least one tumor that can be measured.

Exclusion Criteria

My internal organ cancer symptoms make me ineligible for hormone therapy, according to my doctor.

I have been treated with specific inhibitors before.

My cancer returned over a year after hormone therapy without any treatment for spreading.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alpelisib plus fulvestrant or placebo plus fulvestrant in 28-day cycles until disease progression or other criteria are met

Up to 60 months

Cycle 1 Day 1 and 15, then Day 1 of each cycle

Crossover

Participants in the placebo arm with disease progression may crossover to receive alpelisib plus fulvestrant

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Fulvestrant

Trial Overview The study tests the effectiveness of Alpelisib combined with Fulvestrant versus a placebo plus Fulvestrant in men or postmenopausal women whose advanced breast cancer has worsened despite previous treatments. The goal is to gather more data on this combination's safety and efficacy.

How Is the Trial Designed?

Group I: Alpelisib plus fulvestrant Experimental Treatment 2 Interventions

Alpelisib 300 mg orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15, and on Day 1 on every Cycle thereafter, in a 28 days cycle.

Group II: Alpelisib-matching placebo plus fulvestrant Placebo Group 2 Interventions

Alpelisib-matching placebo orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15 and on Day 1 on every Cycle thereafter, in a 28 days cycle. Participants who have disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover to be treated with alpelisib plus fulvestrant

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?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

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, 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 real-life study of 233 patients with advanced breast cancer who had PIK3CA mutations, treatment with alpelisib and fulvestrant resulted in a median progression-free survival (PFS) of 5.3 months, indicating its efficacy even after multiple prior treatments.

However, 39.1% of patients discontinued alpelisib due to adverse events, highlighting the importance of monitoring for side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program. Bello Roufai, D., Gonçalves, A., De La Motte Rouge, T., et al.[2023]

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, a PI3K-alpha inhibitor, has been approved for use with fulvestrant in patients with HR+/HER2- breast cancer that have PIK3CA mutations, showing improved progression-free survival compared to fulvestrant alone in a phase III trial.

While alpelisib offers a significant benefit in delaying disease progression, its safety profile necessitates careful patient selection and monitoring, particularly regarding glycemic levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. Leenhardt, F., Alexandre, M., Jacot, W.[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]

Citations

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

Alpelisib: First Global Approval. [2020]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program. [2023]

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

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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