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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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

Первичные конечные точки

• Objective Response Rate (ORR) Within Dose Subgroup [Срок оценки: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]
• Duration of Response (DOR) Within Dose Subgroup [Срок оценки: From start date of response (after date of randomization) to first PD, assessed up to 48 months]
• Disease Control Rate (DCR) Within Dose Subgroup [Срок оценки: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]
• Progression Free Survival (PFS) Within Dose Subgroup [Срок оценки: From date of randomization to date of recurrence, progression or death, assessed up to 48 months]
• Overall Survival (OS) Within Dose Subgroup [Срок оценки: From date of randomization to death, assessed up to 48 months]
• Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population [Срок оценки: From date of first dose through last dose plus 28 days, assessed up to 48 months]

Вторичные конечные точки (5)

• Objective Response Rate (ORR) Within Biomarker-Defined Subgroup [Срок оценки: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]
• Duration of Response (DOR) Within Biomarker-Defined Subgroup [Срок оценки: From start date of response (after date of randomization) to first PD, assessed up to 48 months]
• Disease Control Rate (DCR) Within Biomarker-Defined Subgroup [Срок оценки: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months]
• Progression Free Survival (PFS) Within Biomarker-Defined Subgroup [Срок оценки: From date of randomization to date of recurrence, progression or death, assessed up to 48 months]
• Overall Survival (OS) Within Biomarker-Defined Subgroup [Срок оценки: From date of randomization to death, assessed up to 48 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 35 центров

• Alabama Oncology — Birmingham
• Mayo Clinic Hospital — Phoenix
• Beverly Hills Cancer Center — Beverly Hills
• MemorialCare Orange Coast Medical Center — Fountain Valley
• City of Hope at Orange County Lennar Foundation Cancer Center — Irvine
• LA Cancer Network — Los Angeles
• UCLA Department of Medicine - Hematology/Oncology — Los Angeles
• University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Cen — San Francisco
• … и ещё 27 центров

Испания · 14 центров

• Hospital General Universitario Dr. Balmis — Alicante
• Hospital Universitario de Cruces — Barakaldo
• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Clínico de Barcelona — Barcelona
• Hospital Universitario de Basurto — Bilbao
• Hospital San Pedro de Alcántara — Cáceres
• Hospital San Cecilio — Granada
• Hospital Universitario Juan Ramon Jimenez — Huelva
• … и ещё 6 центров

Португалия · 4 центра

• Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa) — Lisbon
• Fundação Champalimaud — Lisbon
• Hospital CUF Descobertas — Lisbon
• Instituto Português Oncologia Do Porto — Porto

Идентификаторы

NCT: NCT06369285 · PUMA-ALI-1201 · 2024-511497-79-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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