Alisertib with Endocrine Therapy for HR-positive, HER2-negative Metastatic Breast Cancer

This study is testing a new combination of medicines, alisertib and endocrine therapy, for people with hormone receptor-positive (HR-positive), HER2-negative metastatic or recurrent breast cancer. This is for patients whose cancer has progressed after at least two previous endocrine therapies. Alisertib is taken by mouth on specific days, along with your doctor's chosen endocrine therapy (like anastrozole or letrozole). The main goals are to see how many people respond to the treatment (Objective Response Rate), how long that response lasts (Duration of Response), and how many people have their disease controlled (Disease Control Rate). The study aims to find the best dose of alisertib and understand its effects. We don't know the current recruitment status.

Study design
This is a randomized, dose optimization, multicenter Phase 2 study. It plans to enroll 225 participants.
What's involved
Alisertib enteric-coated tablets will be taken by mouth twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle. Endocrine therapy will be taken daily in 28-day cycles.
Compensation
Not stated in the trial record.
Follow-up
Responses and disease control will be assessed for up to 48 months (4 years).

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NCT06369285

A Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer

Recruiting
PHASE2Ages 18+InterventionalTreatment
Puma Biotechnology, Inc.
~225 participants
Updated 2026-07-27 on ClinicalTrials.gov
What's tested:AlisertibEndocrine therapy

At a glance

Recruiting sites
52 of 53 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective Response Rate (ORR) Within Dose Subgroup
Measured over From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
+5 more outcomes measured
Hormone Receptor Positive HER-2 Negative Breast Cancer
Metastatic Breast Cancer
Recurrent Breast Cancer
53 sites across 21 states
Spain14
California6
Missouri4
Portugal4
Florida3
Pennsylvania3
Illinois2
Massachusetts2
  • Chief Reg Affairs, PV, Medical Affairs and Law Officer · STUDY_DIRECTOR · Puma Biotechnology, Inc.
Puma Biotechnology, Inc. Clinical Operations Senior Director
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Eligibility criteria

Inclusion

Aged ≥18 years at signing of informed consent.
Pathology-confirmed diagnosis of breast cancer with evidence of recurrent or metastatic disease not amenable to curative therapy.
Progression on or after treatment with at least two prior lines of endocrine therapy in the recurrent or metastatic setting. a. If metastatic disease recurrence occurs during or within six months of discontinuing adjuvant endocrine therapy, then that endocrine therapy will count as one line of prior therapy.
Participants must have received a CDK4/6i in combination with endocrine therapy in the recurrent or metastatic setting.
HR-positive and HER2-negative tumor status reported per local laboratory testing. HR and HER2 testing must be performed consistent with current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society of Medical Oncology (ESMO) guidelines.

Exclusion

Treatment with chemotherapy in the recurrent or metastatic setting, including antibody drug conjugates with a chemotherapeutic payload.
Prior treatment with an Aurora Kinase A (AURKA) specific-targeted or pan-Aurora-targeted agent, including alisertib, in any setting.
  • Objective Response Rate (ORR) Within Dose SubgroupFrom date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months

    Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.

  • Duration of Response (DOR) Within Dose SubgroupFrom start date of response (after date of randomization) to first PD, assessed up to 48 months

    Duration of response is measured from the time at which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.

  • Disease Control Rate (DCR) Within Dose SubgroupFrom date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months

    Disease control rate is the proportion of participants who achieve overall tumor response (confirmed CR or PR) or Stable Disease (SD) lasting for at least 24 weeks from randomization.

  • Progression Free Survival (PFS) Within Dose SubgroupFrom date of randomization to date of recurrence, progression or death, assessed up to 48 months

    Progression Free Survival (PFS) is measured in months and based on the local tumor assessment. The time interval from the date of randomization until the first date on which recurrence, progression, or death due to any cause, is documented.

  • Overall Survival (OS) Within Dose SubgroupFrom date of randomization to death, assessed up to 48 months

    Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.

  • Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled PopulationFrom date of first dose through last dose plus 28 days, assessed up to 48 months

    Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after last dose.