A Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer
- Conditions
- Metastatic Breast CancerHormone Receptor Positive HER-2 Negative Breast CancerRecurrent Breast Cancer
- Interventions
- Drug: Endocrine therapy
- Registration Number
- NCT06369285
- Lead Sponsor
- Puma Biotechnology, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
- 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:
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alisertib 50 mg Alisertib Alisertib with selected endocrine therapy Alisertib 40 mg Alisertib Alisertib with selected endocrine therapy Alisertib 30 mg Endocrine therapy Alisertib with selected endocrine therapy Alisertib 50 mg Endocrine therapy Alisertib with selected endocrine therapy Alisertib 40 mg Endocrine therapy Alisertib with selected endocrine therapy Alisertib 30 mg Alisertib Alisertib with selected endocrine therapy
- Primary Outcome Measures
Name Time Method Duration of Response (DOR) Within Dose Subgroup 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.
Objective Response Rate (ORR) Within Dose Subgroup 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.
Disease Control Rate (DCR) Within Dose Subgroup 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.
Progression Free Survival (PFS) Within Dose Subgroup 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.
Overall Survival (OS) Within Dose Subgroup 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.
Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population 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 Outcome Measures
Name Time Method Progression Free Survival (PFS) Within Biomarker-Defined Subgroup 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.
Overall Survival (OS) Within Biomarker-Defined Subgroup 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.
Objective Response Rate (ORR) Within Biomarker-Defined Subgroup 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.
Duration of Response (DOR) Within Biomarker-Defined Subgroup 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.
Disease Control Rate (DCR) Within Biomarker-Defined Subgroup 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.
Trial Locations
- Locations (41)
Fundación Instituto Valenciano de Oncología (IVO)
🇪🇸Valencia, Spain
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
City of Hope at Orange County Lennar Foundation Cancer Center
🇺🇸Irvine, California, United States
LA Cancer Network
🇺🇸Los Angeles, California, United States
UCLA Department of Medicine - Hematology/Oncology
🇺🇸Los Angeles, California, United States
University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
University of Colorado School of Medicine
🇺🇸Aurora, Colorado, United States
Yale University, Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
The University of Chicago
🇺🇸Chicago, Illinois, United States
Texas Oncology
🇺🇸Dallas, Texas, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Minnesota, Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Oncology Hematology Associates
🇺🇸Springfield, Missouri, United States
Cancer Care Specialists
🇺🇸Reno, Nevada, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
UNC Hospitals, University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
The Ohio State University, Stefanie Spielman Comprehensive Breast Center
🇺🇸Columbus, Ohio, United States
Taylor Cancer Research Center
🇺🇸Maumee, Ohio, United States
Alliance Cancer Specialists
🇺🇸Horsham, Pennsylvania, United States
University of Pennsylvania, Abramson Cancer Center, Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Tennessee Oncology, Greco-Hainsworth Center for Research
🇺🇸Nashville, Tennessee, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Instituto Português Oncologia Do Porto
🇵🇹Porto, Portugal
Hospital General Universitario Dr. Balmis
🇪🇸Alicante, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clínico de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
Hospital San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital San Cecilio
🇪🇸Granada, Spain
Hospital Universitario Juan Ramon Jimenez
🇪🇸Huelva, Spain
Hospital Universitario de Jaén
🇪🇸Jaén, Spain
Hospital Universitario Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Clínico Universitario de Valencia
🇪🇸València, Spain