Hormone Receptor Positive Breast CarcinomaPhase 2NCT04762979

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

A Phase 2 study testing Alpelisib, Fulvestrant and Aromatase inhibitor in people with Hormone Receptor Positive Breast Carcinoma and HER2-negative Breast Cancer, run by Marina N Sharifi at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Hormone Receptor Positive Breast Carcinoma, HER2-negative Breast Cancer, PIK3CA Mutant Metastatic Breast Cancer
What is being tested?: Alpelisib, Fulvestrant and Aromatase inhibitor
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 4 sitesUnited States
Study dates: 12 Feb 2021to May 2026
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of 0-2 within 28 days prior to registration.
Men and postmenopausal female patients. Premenopausal patients (age 18 or older) who have been rendered postmenopausal will also be included. Postmenopausal is defined as:
Age >= 55 years and one year or more of amenorrhea.
Age < 55 years and one year or more of amenorrhea, with estradiol < 20 pg/ml

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Age < 55 years with prior hysterectomy but intact ovaries, with estradiol < 20 pg/ml
Prior bilateral oophorectomy
NOTE: Women who do not fit the criteria for being postmenopausal as above are deemed premenopausal. Premenopausal patients (age 18 or older) who can be rendered postmenopausal will also be eligible. Methods eligible for rending premenopausal patients postmenopausal include:
Ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonist, with treatment starting at least 4 weeks prior to randomization and with estradiol < 20 pg/ml. LHRH agonist must be administered within 7 days of scheduled administration date during the length of the clinical trial.
Histologically confirmed metastatic or unresectable (not amenable to curative therapy) breast cancer.
Has confirmed hormone receptor positivity with ER >=1% and/or PR >=1%. Preferred receptor testing is obtained from a metastatic site, but can be from the primary breast or axilla biopsy as long as this is most recent biopsy.
Has confirmed HER2 negative breast cancer. HER2 negative or non-amplified is determined by the current ASCO-CAP criteria which are as follows: HER2 testing by IHC as 0 or 1+. Or negative by in situ hybridization (FISH/CISH/SISH) defined as Her2/CEP17 ratio <2 and for single probe assessment a HER2 copy number <6). Preferred receptor testing is obtained from a metastatic site, but can be from the primary breast or axilla biopsy as long as this is most recent biopsy.
PIK3CA mutation identified via local testing from tumor tissue or blood.
Has either measurable disease, i.e. at least one measurable lesion as per RECIST 1.1 criteria OR if no measurable disease is present, then at least one predominantly lytic bone lesion must be present, within 28 days prior to registration. Patients with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation.
Has received at least one line of therapy with an endocrine therapy or endocrine therapy combination with other agents in the metastatic setting.
Must have received endocrine therapy (aromatase inhibitor or fulvestrant as single agent or in combination with other agents) as last line of therapy with progressive disease, as determined by treating physician.
No more than two prior lines of endocrine therapy or endocrine therapy combinations in the metastatic setting. Transition from one nonsteroidal aromatase inhibitor to a second nonsteroidal aromatase inhibitor due to tolerance will only count as one line of endocrine therapy. Combination therapy will be considered one line even if one of the agents is discontinued and the other continued.
Patient must have received treatment with a CDK4/6 inhibitor for breast cancer in the metastatic setting. CDK4/6 inhibitor discontinuation due to intolerance or reasons other than progression is allowed.
Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Acceptable forms of contraception include castration, vasectomy, and condom/occlusive cap with spermicidal foam/gel/film/cream/suppository. Male patients with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least one month after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
Premenopausal females must agree to use an acceptable method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 3 months after discontinuation of therapy. Adequate forms of contraception include: total abstinence, surgery intended to prevent pregnancy (defined as hysterectomy, bilateral oophorectomy or bilateral tubal ligation), non-hormonal IUD, or condom/occlusive cap with spermicidal foam/gel/film/cream/suppository).
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.

Who cannot join

Patients with prior chemotherapy for metastatic or advanced disease.
Active infection requiring systemic therapy.
Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
Uncontrolled, active CNS metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease.
NOTE: Subjects who are symptomatic and have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) within 28 days prior to registration to exclude brain metastases.
Treatment with any investigational drug within 14 days prior to registration.

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Radiotherapy to index lesion <= 4 weeks or limited field radiation to index lesion for palliation <= 2 weeks prior to randomization.
Established diagnosis of diabetes mellitus type I or persistent poorly controlled diabetes mellitus, with an uninterrupted hemoglobin A1c > 8.0% for 1 year or greater despite standard care. For patients with newly diagnosed diabetes mellitus without 1 year of hemoglobin A1c values, available hemoglobin A1c values cannot all be > 8.0%.
Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
As determined by the enrolling physician or protocol designee, impairment of gastrointestinal function or disease that may significantly alter the absorption of the study drugs.
Currently documented clinically active pneumonitis. Patients could have received prior treatment for pneumonitis but pneumonitis must have clinically resolved and treatments for pneumonitis (e.g. steroids) must be completed prior to randomization.
Active cardiac disease, defined as any of the following within 6 months prior to the start of study treatment:
History of angina pectoris, coronary artery bypass graft, symptomatic pericarditis, or myocardial infarction.
History of documented congestive heart failure (New York Heart Association functional classification III-IV).
History of any cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality.
Systolic blood pressure (SBP) >180 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg at screening. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
History of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis.
Prior treatment with PI3K, mTOR or AKT inhibitor in the metastatic setting.
History of chronic steroid use (defined as daily steroid use > 14 days) and requirement for continued chronic steroid use.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

University of Illinois Cancer Center
Chicago, Illinois, 60612
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
University of Wisconsin
Madison, Wisconsin, 53705
University of Nebraska Medical Center
Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: A Phase II, Single Arm, Non-randomized Study of Alpelisib (BYL719) in Combination With Continued Endocrine Therapy Following Progression on Endocrine Therapy in Hormone Receptor Positive, HER2 Negative, PIK3CA Mutant Metastatic Breast Cancer

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.

Conditions: Hormone Receptor Positive Breast Carcinoma, HER2-negative Breast Cancer, PIK3CA Mutant Metastatic Breast Cancer
Being tested: Alpelisib, Fulvestrant, Aromatase inhibitor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AlpelisibDrug
Alpelisib 300mg, PO, days 1-28 of each cycle.
FulvestrantDrug
Fulvestrant 500mg, IM, once monthly
Aromatase inhibitorDrug
Aromatase Inhibitor, administered per standard of care

Study groups in NCT04762979
Study group	Role	What they receive
Alpelisib + Aromatase Inhibitor or Fulvestrant	Experimental	Subjects will be treated with Alpelisib in combination with either an Aromatase Inhibitor or Fulvestrant per Standard of Care Receives: Drug: Alpelisib; Drug: Fulvestrant; Drug: Aromatase inhibitor

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression-Free Survival (PFS)
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.
Measured: From enrollment until the time of disease progression, up to 60 months

Secondary outcomes (5)

Objective Response Rate (ORR)
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
Measured: From enrollment until the time of disease progression, up to 60 months
Clinical Benefit Rate (CBR)
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.
Measured: From enrollment until the time of disease progression, up to 60 months
Duration of Response (DOR)
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.
Measured: From enrollment until the time of disease progression, up to 60 months
Overall Survival (OS)
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.
Measured: From enrollment until the time of death, up to 60 months
Safety Profile of alpelisib with continued endocrine therapy(aromatse inhibitor or fulvestrant)
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.
Measured: From enrollment until 30 days after completion of study therapy or subject withdrawal, up to seven months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Feb 2021May 2026

First posted21 Feb 2021
Study start12 Feb 2021
Primary completion23 Oct 2025
Study completionMay 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hormone Receptor Positive Breast CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Apelisib 300mg PO, Daily AND Aromatices Inhibitor(AI) or Fulvestrant 500mg IM per Standard of Care
Masking: None (open label)
Enrolment: 44 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04762979
Sponsor's protocol ID: BTCRC-BRE19-409
Status last verified: Dec 2025
First submitted: 17 Feb 2021
Last updated: 2 Jan 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
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Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
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Geriatric Oncology Assessment and Coping Skills Training for Older Women on Aromatase Inhibitor Therapy
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Patient Relevant Outcomes Improvement Program in High Risk Hormone Receptor Positive (HR+) Breast Cancer
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RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
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All Hormone Receptor Positive Breast Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Single Arm, Non-randomized Study of Alpelisib (BYL719) in Combination With Continued Endocrine Therapy Following Progression on Endocrine Therapy in Hormone Receptor Positive, HER2 Negative, PIK3CA Mutant Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT04762979
Acronym / sponsor ID: BTCRC-BRE19-409
Conditions: Hormone Receptor Positive Breast Carcinoma, HER2-negative Breast Cancer, PIK3CA Mutant Metastatic Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 44 participants (estimated)
Lead sponsor: Marina N SharifiUniversity, hospital or other
Collaborators: Novartis, University of Wisconsin, Madison
Study start: 12 Feb 2021 (actual)
Primary completion: 23 Oct 2025 (actual)
Study completion: May 2026 (estimated)
First posted: 21 Feb 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Apelisib 300mg PO, Daily AND Aromatices Inhibitor(AI) or Fulvestrant 500mg IM per Standard of Care

Arm	Type	Receives
Alpelisib + Aromatase Inhibitor or Fulvestrant	Experimental	Drug: Alpelisib, Drug: Fulvestrant, Drug: Aromatase inhibitorSubjects will be treated with Alpelisib in combination with either an Aromatase Inhibitor or Fulvestrant per Standard of Care

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (24 listed)

Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of 0-2 within 28 days prior to registration.
Men and postmenopausal female patients. Premenopausal patients (age 18 or older) who have been rendered postmenopausal will also be included. Postmenopausal is defined as:
NOTE: Women who do not fit the criteria for being postmenopausal as above are deemed premenopausal. Premenopausal patients (age 18 or older) who can be rendered postmenopausal will also be eligible. Methods eligible for rending premenopausal patients postmenopausal include:

Key exclusion criteria (19 listed)

Patients with prior chemotherapy for metastatic or advanced disease.
Active infection requiring systemic therapy.
Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
Uncontrolled, active CNS metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease.
NOTE: Subjects who are symptomatic and have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) within 28 days prior to registration to exclude brain metastases.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AlpelisibAlpelisib 300mg, PO, days 1-28 of each cycle.	Drug	Alpelisib + Aromatase Inhibitor or Fulvestrant
FulvestrantFulvestrant 500mg, IM, once monthly	Drug	Alpelisib + Aromatase Inhibitor or Fulvestrant
Aromatase inhibitorAromatase Inhibitor, administered per standard of care	Drug	Alpelisib + Aromatase Inhibitor or Fulvestrant

Primary outcome

Progression-Free Survival (PFS)
Time frame: 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.

5 secondary outcomes

Objective Response Rate (ORR)
Time frame: From enrollment until the time of disease progression, up to 60 months
Clinical Benefit Rate (CBR)
Time frame: From enrollment until the time of disease progression, up to 60 months
Duration of Response (DOR)
Time frame: From enrollment until the time of disease progression, up to 60 months
Overall Survival (OS)
Time frame: From enrollment until the time of death, up to 60 months
Safety Profile of alpelisib with continued endocrine therapy(aromatse inhibitor or fulvestrant)
Time frame: From enrollment until 30 days after completion of study therapy or subject withdrawal, up to seven months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
Individual participant dataSharing planned: No

Related trials for Hormone Receptor Positive Breast Carcinoma

RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer
Not yet recruiting
Geriatric Oncology Assessment and Coping Skills Training for Older Women on Aromatase Inhibitor Therapy
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RecruitingObservational study
Patient Relevant Outcomes Improvement Program in High Risk Hormone Receptor Positive (HR+) Breast Cancer
HR+/HER2- Early Breast Cancer
RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marina N Sharifi, MD principal investigator

University of Wisconsin, Madison

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: From enrollment until the time of disease progression, up to 60 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04762979.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026.