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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Study 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.

Eligibility

Primary outcome measure(s)

• 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.

Trial sites (53)

+ 13 more sites — see the full list on the official registry below.

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