Alpelisib + Fulvestrant for Breast Cancer

(EPIK-B5 Trial)

Not currently recruiting at 100 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two drugs, alpelisib (Piqray) and fulvestrant (Faslodex), for individuals with a specific type of advanced breast cancer. The goal is to determine if these drugs can better manage HR-positive, HER2-negative breast cancer with a PIK3CA mutation, particularly in cases where the cancer worsened after previous treatments. Participants will receive either the drug combination or a placebo (a harmless pill with no active drug) alongside fulvestrant. The trial seeks men and postmenopausal women whose cancer has returned or progressed after certain past treatments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that alpelisib and fulvestrant are likely to be safe for humans?

Research shows that alpelisib combined with fulvestrant treats a specific type of breast cancer. This treatment targets a gene change called PIK3CA, common in some breast cancers. The FDA has approved alpelisib for breast cancer, indicating a known safety record.

Studies have found that patients generally tolerate alpelisib well. However, some may experience side effects like high blood sugar, rash, and diarrhea, which can be managed with proper medical care. Discussing any concerns with a doctor is important to understand the possible risks and benefits.

Overall, safety data indicates that alpelisib plus fulvestrant has been thoroughly studied in breast cancer patients, providing extensive information about patient responses to the treatment. ^{1 2 3 4 5}

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

Researchers are excited about Alpelisib combined with Fulvestrant for breast cancer because it targets a specific pathway often involved in cancer cell growth. Alpelisib is a PI3K inhibitor, which means it works by blocking the PI3K enzyme that can promote cancer growth, especially in hormone receptor-positive breast cancers. This approach is different from standard treatments like chemotherapy, which attack all rapidly dividing cells, or hormone therapies that only target estrogen receptors. By focusing on the PI3K pathway, Alpelisib offers a more targeted attack on cancer cells, potentially leading to fewer side effects and improved effectiveness for patients with certain genetic profiles.

What evidence suggests that alpelisib plus fulvestrant could be an effective treatment for advanced breast cancer?

Research shows that combining alpelisib with fulvestrant effectively treats certain advanced breast cancers. In this trial, participants will receive either the combination of alpelisib and fulvestrant or an alpelisib-matching placebo with fulvestrant. One study found that this combination nearly doubled the time patients lived without their cancer worsening, particularly for those with a PIK3CA mutation. Real-world data also supports its effectiveness in patients who have already tried other treatments. In the SOLAR-1 trial, this combination significantly slowed cancer progression. Overall, the treatment has proven highly effective for patients with hormone receptor-positive, HER2-negative breast cancer that has specific genetic changes. ^{1 2 4 6 7}

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. After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.

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, 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 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]

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 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, 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]

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]

Citations

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

Real world outcomes with alpelisib in metastatic hormone ... The median duration of response was 5.77 months (range: 5.54, 8.98). At the time of this report, 8/27 (29.6%) patients had died, and all deaths were attributed ...

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 PIQRAY + fulvestrant nearly doubled mPFS in patients with a PIK3CA driver mutation. At the prespecified final OS analysis, there was no significant difference ...

4. 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 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13053

Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL ... Conclusions: ALP+FUL demonstrated high efficacy in heavily pretreated pts with HR+/HER2- ABC with PIK3CAm in routine practice. ALP+FUL should be ...

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

Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive ... A total of 5 patients receiving alpelisib–fulvestrant and 8 receiving placebo–fulvestrant died from underlying breast cancer. Other deaths in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02437318

NCT02437318 | Study Assessing the Efficacy and Safety of ... This was a randomized, double-blind, placebo-controlled, international multicenter Phase III study that evaluated the efficacy and safety of treatment with ...