Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06369285

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

PUMA-ALI-1201 is a randomized, dose optimization, multicenter, Phase 2 study of alisertib administered in combination with endocrine therapy in participants with pathology-confirmed HR-positive/HER2-negative metastatic breast cancer (MBC) following progression on or after at least two prior lines of endocrine therapy in the recurrent or metastatic setting. This study is intended to evaluate the optimal alisertib dose administered in combination with the selected endocrine therapy. The study is also planned to evaluate the efficacy, safety, and pharmacokinetics of alisertib in combination with endocrine and to identify the biomarker-defined subgroup(s) that may benefit most from combined alisertib and endocrine therapy. Participants randomized prior to Amendment 4 are randomized 1:1:1 to Arm 1, Arm 2 or Arm 3. Participants randomized under Amendment 4 will be randomized 1:1 to Arm 1 or Arm 2.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Hormone Receptor Positive HER-2 Negative Breast Cancer Breast Diseases Breast Neoplasms Metastatic Breast Cancer Neoplasms Neoplasms by Site Recurrent Breast Cancer Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Fundação Champalimaud, Lisbon, Portugal

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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 criteria

  • 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.

Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Treatment and study plan

Alisertib

Drug

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.

Other names: PB-8237, MLN8237

endocrine therapy

Drug

Investigator selected endocrine therapy will be taken in 28-day dosing cycles according to the approved prescribing information.

1 mg of anastrozole tablet by mouth once daily or

2.5 mg of letrozole tablet by mouth once daily or

25 mg of exemestane tablet by mouth once daily or

20 mg of tamoxifen tablet by mouth once daily or

500 mg of fulvestrant intramuscular injection on Study Day 1, 15, 29, and once every 28 days thereafter

Primary outcomes

  1. Objective Response Rate (ORR) Within Dose Subgroup

    Time frame: From 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.

  2. Duration of Response (DOR) Within Dose Subgroup

    Time frame: From 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.

  3. Disease Control Rate (DCR) Within Dose Subgroup

    Time frame: From 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.

  4. Progression Free Survival (PFS) Within Dose Subgroup

    Time frame: From 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.

  5. Overall Survival (OS) Within Dose Subgroup

    Time frame: From 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.

  6. Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population

    Time frame: From 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.

Secondary outcomes

  1. Objective Response Rate (ORR) Within Biomarker-Defined Subgroup

    Time frame: From 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.

  2. Duration of Response (DOR) Within Biomarker-Defined Subgroup

    Time frame: From 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 CR or PR (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.

  3. Disease Control Rate (DCR) Within Biomarker-Defined Subgroup

    Time frame: From 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 SD lasting for at least 24 weeks from randomization.

  4. Progression Free Survival (PFS) Within Biomarker-Defined Subgroup

    Time frame: From 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.

  5. Overall Survival (OS) Within Biomarker-Defined Subgroup

    Time frame: From 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Puma Biotechnology, Inc. Clinical Operations Senior Director

CONTACT

[email protected]

424-248-6500

Sponsors and collaborators

Lead sponsor

Puma Biotechnology, Inc.

Industry

Registry information

Official study title

A Phase 2 Study of Alisertib in Combination With Endocrine Therapy in Patients With HR+, HER2-negative Recurrent or Metastatic Breast Cancer

Acronym: ALISCA-Breast1

Important dates

Study start
2024
Primary completion
2027
Study completion
2029
First posted
Apr 16, 2024
Registry last updated
Jul 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.