BYL719 + Letrozole for Breast Cancer

Not currently recruiting at 1 trial location
Age: 18+
Sex: Female
Trial Phase: Phase 1
Sponsor: Vanderbilt-Ingram Cancer Center
Must be taking: Letrozole
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and side effects of a new drug combination for hormone receptor-positive metastatic breast cancer. The combination includes the PI3K inhibitor BYL719, which blocks proteins necessary for tumor growth, and letrozole, a hormone therapy that prevents tumors from using estrogen. Post-menopausal women with advanced hormone receptor-positive breast cancer who have previously undergone at least one type of hormone therapy may be suitable candidates. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug combination.

Do I need to stop my current medications to join the trial?

The trial requires that you stop certain medications before joining. You must stop any systemic anti-cancer therapy, hormonal therapy, and herbal medications at least 2-4 weeks before starting the trial. Also, you cannot take medications that affect the heart's QT interval unless they can be switched or stopped before the trial.

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

Research has shown that using BYL719 (also known as alpelisib) with letrozole is safe and generally well-tolerated for treating hormone receptor-positive metastatic breast cancer. Studies have found that patients can undergo this treatment without experiencing many serious side effects.

In one study, the most common issues were manageable and included nausea and tiredness. Researchers determined that the highest safe dose of BYL719 is 300 milligrams per day when used with letrozole, indicating that most people could take this amount without too much discomfort.

Overall, early results suggest that this combination treatment is promising and does not cause major safety concerns.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of BYL719 and letrozole for breast cancer because it targets the PI3K pathway, which is often overactive in cancer cells. While standard treatments like hormone therapy focus on blocking estrogen receptors, BYL719 is a PI3K inhibitor that may directly interfere with cancer cell growth and survival. This dual approach—using letrozole to reduce estrogen production and BYL719 to inhibit a critical cancer growth pathway—has the potential to be more effective than current hormone therapies alone.

What evidence suggests that BYL719 + Letrozole might be an effective treatment for breast cancer?

This trial will evaluate the combination of BYL719 (alpelisib) and letrozole for treating hormone receptor-positive metastatic breast cancer. Studies have shown that this combination is promising, especially for patients with a specific genetic change called PIK3CA, where 44% experienced benefits, meaning their cancer did not worsen for at least six months. Specifically, this combination led to an average of about 5.7 months before the cancer began growing again. Research indicates that BYL719 blocks proteins that aid cancer cell growth, while letrozole prevents tumor cells from using estrogen. This combination is considered safe and manageable for patients with this type of breast cancer.14678

Who Is on the Research Team?

VICC's Mayer departing to take new role ...

Ingrid A Mayer, MD

Principal Investigator

Vanderbilt-Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for post-menopausal women with hormone receptor-positive metastatic breast cancer. Participants must have had prior endocrine therapy, be able to swallow pills, and have a life expectancy of at least 6 months. They need proper organ function and no severe heart conditions or uncontrolled illnesses.

Inclusion Criteria

Life expectancy ≥ 6 months
Patients must provide informed written consent
ANC >/= 1,500/mm3
See 23 more

Exclusion Criteria

ST depression or elevation of ≥ 1.5 mm in 2 or more leads
Left Ventricular Ejection Fraction (LVEF) < 50%
I had radiation therapy more than 2 weeks ago and have recovered from its side effects.
See 25 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BYL719 and letrozole orally once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

8 weeks
Weekly monitoring for dose-limiting toxicities

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

  • BYL719
  • Letrozole
Trial Overview The study is testing the combination of BYL719 (a PI3K inhibitor) and letrozole to see if they are more effective together in stopping tumor growth compared to standard treatments. The trial will also determine the safest doses of BYL719 when used with letrozole.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (PI3K inhibitor BYL719, letrozole)Experimental Treatment4 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials
221
Recruited
64,400+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/27126994/
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα ... - PubMedThis phase Ib study evaluated alpelisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER + breast cancer ...
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific ...The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%–56%), ...
SU2C phase Ib study of the PI3Kα inhibitor BYL719 with ...Conclusions: The combination of letrozole/ BYL719 is safe and tolerable in pts with AI-refractory ER+/HER2 MBC. The MTD and recommended dose for ...
Alpelisib/Letrozole Combo Sustains Efficacy in PIK3CA- ...With a median follow-up of 15 months, the combination of alpelisib and letrozole resulted in a median progression-free survival (PFS) of 5.7 ...
NCT05038735 | Study to Assess the Efficacy and Safety of ...The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) ...
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific ...The results from this study provide evidence that alpelisib plus letrozole is safe, tolerable, and active in postmenopausal patients with ER+/HER2 ...
NCT03056755 | Study Assessing the Efficacy and Safety of ...This was a Phase II, multicenter, open-label, three-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in ...
AACR 2015: Adding PI3K inhibitor BYL719 to letrozole was ...The researchers found that the maximum-tolerated dose of BYL719 in combination with letrozole was 300 milligrammes per day. The most frequent ...
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