Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

What this trial studies

This was a Phase II, multicenter, open-label, three-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in subjects (pre- and post-menopausal women and men) with HR-positive, HER2-negative aBC harboring PIK3CA mutation(s) in the tumor, whose disease had progressed on or after prior treatments.

Conditions in scope

• Breast Cancer

Interventions

• Alpelisib (Drug) — 300 mg of alpelisib film-coated tablets administered orally once daily
• Fulvestrant (Drug) — 500 mg of fulvestrant via intramuscular injection administered on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter. Cycle=28 days
• Letrozole (Drug) — 2.5 mg of letrozole film-coated tablets administered orally once daily
• Goserelin (Drug) — 3.6 mg of goserelin via injectable subcutaneous implant administered every 28 days. Only for men in Cohort B and premenopausal women.
• Leuprolide (Drug) — 7.5 mg of leuprolide via injectable intramuscular depot administered every 28 days. Only for men in cohort B and premenopausal women.

Who can join

All sexes · Ages 18 Years to 99 Years

Inclusion criteria

• Subject was an adult male or female ≥ 18 years of age.
• Subjects with histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive breast cancer by local laboratory.
• Subjects with a confirmed human epidermal growth factor receptor-2 (HER2)-negative aBC.
• Subjects with gene encoding the p110alpha catalytic subunit of PI3K (phosphatidylinositol-3-kinase) (PIK3CA) mutation.
• In case of women, both premenopausal and postmenopausal subjects were allowed to be included in this study.
• Subjects with documented evidence of tumor progression on or after:
• i. Cyclin-Dependent Kinase 4 and 6 inhibitor (CDK4/6i) treatment as last treatment regimen in Cohorts A and B.
• ii. aromatase inhibitor (AI) treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET (monotherapy or combination except CDK4/6i + AI) as last treatment regimen in Cohort C. Upon completion of enrollment of Cohort B, subjects who received CDK4/6i + fulvestrant as immediate prior therapy were eligible for Cohort C.

Exclusion criteria

• Subjects with a known hypersensitivity to alpelisib, fulvestrant, letrozole, goserelin, or leuprolide or to any of their excipients.
• Subjects with prior treatment with any PI3K inhibitor (PI3Ki).
• Subjects with central nervous system (CNS) involvement unless they met all of the following criteria:
• i. At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment, ii. Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (magnetic resonance imaging (MRI) or computed tomography (CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment.
• Subjects with an established diagnosis of diabetes mellitus type I or uncontrolled type II.
• Any concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate subject participation in the study (e.g., chronic active hepatitis, severe hepatic impairment, etc.).
• Subjects with a history of noncompliance to medical regimens.
• Subjects with impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of the study drugs based on investigator discretion.

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Showing the first 10 of 94 sites. See all sites on ClinicalTrials.gov.

Status & timeline

• Overall status: Completed
• Study type: Interventional
• Phase: PHASE2
• Start date: 2017-08-29
• Primary completion: 2021-06-14
• Last update posted: 2026-01-13
• First posted: 2017-02-17

Sponsor & contact

Lead sponsor: Novartis Pharmaceuticals (Industry)

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• Core Phase: Percentage of Participants Who Were Alive Without Disease Progression at 6 Months (At 6 months)
  Percentage of participants who were alive without disease progression at 6-month follow-up based on local investigator assessment per RECIST v1.1 in Cohort A, Cohort B and Cohort C. Participants who progressed, died, or discontinued study before 6 months were counted as a failure.

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