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

NCT04762979 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BTCRC-BRE19-409
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 4

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.

Conditions

Hormone Receptor Positive Breast Carcinoma; HER2-negative Breast Cancer; PIK3CA Mutant Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment until the time of disease progression, up to 60 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  From enrollment until the time of disease progression, up to 60 months

• Clinical Benefit Rate (CBR)

  From enrollment until the time of disease progression, up to 60 months

• Duration of Response (DOR)

  From enrollment until the time of disease progression, up to 60 months

• Overall Survival (OS)

  From enrollment until the time of death, up to 60 months

• 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

Study Arms (1)

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

Drug: Alpelisib; Drug: Fulvestrant; Drug: Aromatase inhibitor

Interventions

Alpelisib DRUG

Alpelisib 300mg, PO, days 1-28 of each cycle.

Alpelisib + Aromatase Inhibitor or Fulvestrant

Fulvestrant DRUG

Fulvestrant 500mg, IM, once monthly

Alpelisib + Aromatase Inhibitor or Fulvestrant

Aromatase inhibitor DRUG

Aromatase Inhibitor, administered per standard of care

Alpelisib + Aromatase Inhibitor or Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Marina N Sharifi: lead
• Novartis: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (4)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Interventions

Alpelisib; Fulvestrant; Aromatase Inhibitors

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Marina N Sharifi, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: Apelisib 300mg PO, Daily AND Aromatices Inhibitor(AI) or Fulvestrant 500mg IM per Standard of Care

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 21, 2021
• Study Start: February 12, 2021
• Primary Completion: October 23, 2025
• Study Completion: May 1, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)