Hormone Receptor Positive HER-2 Negative Breast Cancer, Metastatic Breast Cancer, Recurrent Breast Cancer
Conditions
Keywords
Hormone receptor positive (HR+), Human epidermal growth factor receptor 2 negative (HER2-), Recurrent Breast Cancer, Metastatic Breast Cancer
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. 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.
Interventions
DRUGAlisertib
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.
DRUGEndocrine 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
Sponsors
Puma Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Portugal, Spain, United States
Contacts
CONTACTPuma Biotechnology, Inc. Clinical Operations Senior Director
STUDY_DIRECTORChief Reg Affairs, PV, Medical Affairs and Law Officer
Puma Biotechnology, Inc.
Outcome results
None listed