Clinical trial NCT06369285: A Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer
Official title: A Phase 2 Study of Alisertib in Combination With Endocrine Therapy in Patients With HR+, HER2-negative Recurrent or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hormone Receptor Positive HER-2 Negative Breast Cancer
Metastatic Breast Cancer
Recurrent Breast Cancer
Keywords: Hormone receptor positive (HR+)
Human epidermal growth factor receptor 2 negative (HER2-)
Recurrent Breast Cancer
Metastatic Breast Cancer
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) Within Dose Subgroup
timeFrame: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
measure: Duration of Response (DOR) Within Dose Subgroup
timeFrame: From start date of response (after date of randomization) to first PD, assessed up to 48 months
measure: Disease Control Rate (DCR) Within Dose Subgroup
timeFrame: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
measure: Progression Free Survival (PFS) Within Dose Subgroup
timeFrame: From date of randomization to date of recurrence, progression or death, assessed up to 48 months
measure: Overall Survival (OS) Within Dose Subgroup
timeFrame: From date of randomization to death, assessed up to 48 months
measure: Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population
timeFrame: From date of first dose through last dose plus 28 days, assessed up to 48 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Within Biomarker-Defined Subgroup
timeFrame: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
measure: Duration of Response (DOR) Within Biomarker-Defined Subgroup
timeFrame: From start date of response (after date of randomization) to first PD, assessed up to 48 months
measure: Disease Control Rate (DCR) Within Biomarker-Defined Subgroup
timeFrame: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
measure: Progression Free Survival (PFS) Within Biomarker-Defined Subgroup
timeFrame: From date of randomization to date of recurrence, progression or death, assessed up to 48 months
measure: Overall Survival (OS) Within Biomarker-Defined Subgroup
timeFrame: From date of randomization to death, assessed up to 48 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Irvine
country: United States
facility: City of Hope at Orange County Lennar Foundation Cancer Center
state: California
city: Los Angeles
country: United States
facility: LA Cancer Network
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology/Oncology
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Reno
country: United States
facility: Cancer Care Specialists
state: Nevada
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals, University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University, Stefanie Spielman Comprehensive Breast Center
state: Ohio
city: Maumee
country: United States
facility: Taylor Cancer Research Center
state: Ohio
city: Horsham
country: United States
facility: Alliance Cancer Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center, Perelman Center for Advanced Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, Greco-Hainsworth Center for Research
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas
city: Porto
country: Portugal
facility: Instituto Português Oncologia Do Porto
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínico de Barcelona
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Granada
country: Spain
facility: Hospital San Cecilio
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramon Jimenez
city: Jaén
country: Spain
facility: Hospital Universitario de Jaén
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología (IVO)
city: València
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Puma Biotechnology, Inc.
name: Chief Reg Affairs, PV, Medical Affairs and Law Officer
role: STUDY_DIRECTOR
References: