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

Metastatic Breast Cancer Clinical Trial

— ALISCA-Breast1  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06369285
• Other study ID #: PUMA-ALI-1201
• Secondary ID: 2024-511497-79-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 31, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2024
• Source: Puma Biotechnology, Inc.
• Contact: Puma Biotechnology, Inc. Clinical Operations Senior Director
• Phone: 424-248-6500
• Email: ClinicalTrials[@]pumabiotechnology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: December 31, 2028
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged =18 years at signing of informed consent.
• Pathology-confirmed diagnosis of adenocarcinoma of the breast 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.
• 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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Hormone Receptor Positive HER-2 Negative Breast Cancer
• Metastatic Breast Cancer
• Recurrence
• Recurrent Breast Cancer

Intervention

Drug:
• Alisertib
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
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

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Within Dose Subgroup	Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
Primary	Duration of Response (DOR) Within Dose Subgroup	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.	From start date of response (after date of randomization) to first PD, assessed up to 48 months
Primary	Disease Control Rate (DCR) Within Dose Subgroup	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.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
Primary	Progression Free Survival (PFS) Within Dose Subgroup	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.	From date of randomization to date of recurrence, progression or death, assessed up to 48 months
Primary	Overall Survival (OS) Within Dose Subgroup	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.	From date of randomization to death, assessed up to 48 months
Primary	Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population	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.	From date of first dose through last dose plus 28 days, assessed up to 48 months
Secondary	Objective Response Rate (ORR) Within Biomarker-Defined Subgroup	Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
Secondary	Duration of Response (DOR) Within Biomarker-Defined Subgroup	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.	From start date of response (after date of randomization) to first PD, assessed up to 48 months
Secondary	Disease Control Rate (DCR) Within Biomarker-Defined Subgroup	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.	From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
Secondary	Progression Free Survival (PFS) Within Biomarker-Defined Subgroup	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.	From date of randomization to date of recurrence, progression or death, assessed up to 48 months
Secondary	Overall Survival (OS) Within Biomarker-Defined Subgroup	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.	From date of randomization to death, assessed up to 48 months