Alpelisib (BYL719) in Combination With Continued Endocrine Therapy Following Progression on Endocrine Therapy in Hormone Receptor Positive, HER2 Negative, PIK3CA Mutant Metastatic Breast Cancer

Phase 2

Recruiting

• Conditions: PIK3CA Mutant Metastatic Breast Cancer; Hormone Receptor Positive Breast Carcinoma; HER2-negative Breast Cancer
• Interventions: Drug: Alpelisib; Drug: Fulvestrant; Drug: Aromatase inhibitor

• Registration Number: NCT04762979
• Lead Sponsor: Marina N Sharifi

Brief Summary

Patients who have histologically confirmed metastatic or unresectable (not amenable to curative therapy) breast cancer may be screened for eligibility. All patients must have HER2 negative breast cancer with the identified PIK3CA mutation and received at least one line of endocrine therapy. The study will consist of a screening phase, a treatment phase, and a post-treatment phase which includes safety, efficacy, and follow-up. The treatment phase will include taking alpelisib daily in combination with continued use of either Fulvestrant or Aromatase Inhibitor per standard of care until disease progression or unacceptable toxicity.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-12
• Study First Submitted: 2021-02-17
• Study First Submitted QC: 2021-02-17
• Study First Posted: 2021-02-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-29
• Last Update Posted: 2024-10-30
• Primary Completion: 2025-09
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Alpelisib + Aromatase Inhibitor or Fulvestrant	Alpelisib	Subjects will be treated with Alpelisib in combination with either an Aromatase Inhibitor or Fulvestrant per Standard of Care
Alpelisib + Aromatase Inhibitor or Fulvestrant	Fulvestrant	Subjects will be treated with Alpelisib in combination with either an Aromatase Inhibitor or Fulvestrant per Standard of Care
Alpelisib + Aromatase Inhibitor or Fulvestrant	Aromatase inhibitor	Subjects will be treated with Alpelisib in combination with either an Aromatase Inhibitor or Fulvestrant per Standard of Care

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	From enrollment until the time of disease progression, up to 60 months	To estimate the progression-free survival (PFS) of alpelisib with continued endocrine therapy (aromatase inhibitor or fulvestrant) following progression in patients with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer. PFS defined as time from D1 of treatment with alpelisib with endocrine therapy.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	From enrollment until the time of disease progression, up to 60 months	To estimate the objective response rate (ORR) of alpelisib with continued endocrine therapy (aromatase inhibitor or fulvestrant) following progression in patients with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer. ORR will include confirmed complete response (CR) and confirmed partial response (PR) as determined by RECIST 1.1
Clinical Benefit Rate (CBR)	From enrollment until the time of disease progression, up to 60 months	To estimate the clinical benefit rate (CBR) of alpelisib with continued endocrine therapy (aromatase inhibitor or fulvestrant) following progression in patients with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer. CBR will include the sum of CR + PR + stable disease (SD) on treatment with alpelisib with endocrine therapy.
Duration of Response (DOR)	From enrollment until the time of disease progression, up to 60 months	To estimate the duration of response (DoR) of alpelisib with continued endocrine therapy (aromatase inhibitor or fulvestrant) following progression in patients with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer. DOR is defined as the time that measurement criteria are met CR or PR (whichever status is recorded first) until the date that recurrent or progressive disease PD) is objectively documented.
Overall Survival (OS)	From enrollment until the time of death, up to 60 months	To estimate the overall survival (OS) of alpelisib with continued endocrine therapy (aromatase inhibitor or fulvestrant) following progression in patients with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer. OS is defined as the time from treatment initiation with alpelisib with endocrine therapy following progression until death as a result of any cause.
Safety Profile of alpelisib with continued endocrine therapy(aromatse inhibitor or fulvestrant)	From enrollment until 30 days after completion of study therapy or subject withdrawal, up to seven months	To estimate grade 3-4 adverse events or events of any grade leading to dose adjustments of alpelisib with continued endocrine therapy (aromatase inhibitor or fulvestrant) following progression in patients with hormone receptor positive, HER2 negative, PIK3CA mutant metastatic breast cancer. Grade 3-4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 or events of any grade leading to dose adjustments.

Trial Locations

Locations (4)

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

University of Illinois Cancer Center; 🇺🇸 Chicago, Illinois, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Penn State Cancer Institute; 🇺🇸 Hershey, Pennsylvania, United States