Sponsor: Puma Biotechnology, Inc. (industry)
Phase: 2
Start date: Nov. 19, 2024
Planned enrollment: 150
Alisertib (MLN8237) is an investigational oral cancer drug studied in several solid tumors and blood cancers. Human trials have shown tumor responses, but results vary by cancer type. A phase 3 trial in peripheral T-cell lymphoma did not establish a benefit over the treatments used for comparison. (ascopubs.org)
Alisertib inhibits Aurora A kinase (AURKA), a protein involved in organizing the mitotic spindle and controlling cell division. Inhibiting it can disrupt chromosome segregation and lead to cancer-cell death or senescence. (haematologica.org)
Low blood-cell counts are a prominent risk. In Lumiere, anemia occurred in 53% of alisertib recipients versus 34% of comparator recipients, and neutropenia in 47% versus 31%. In the small-cell lung cancer combination trial, grade 3 or higher drug-related adverse events occurred in 67% with alisertib plus paclitaxel versus 22% with paclitaxel plus placebo; investigators reported four treatment-related deaths in the alisertib arm and none in the control arm. Risks may differ across doses and combinations. (ascopubs.org)
Last updated: Sep 2026
Goal: Identify an optimal dose of alisertib combined with endocrine therapy for HR-positive, HER2-negative recurrent or metastatic breast cancer, and assess efficacy, safety, pharmacokinetics, and potential biomarkers of benefit.
Patients: Adults with pathology-confirmed HR-positive, HER2-negative recurrent or metastatic breast cancer not amenable to curative therapy. Patients must have progressed on or after at least two prior endocrine therapy lines and received a CDK4/6 inhibitor with endocrine therapy in the recurrent or metastatic setting. Prior chemotherapy for recurrent or metastatic disease or prior Aurora kinase–targeted therapy is excluded.
Design: Multicenter, randomized dose-optimization study comparing three alisertib doses, each given with selected endocrine therapy. There is no endocrine-therapy-only arm.
Treatments: Patients receive alisertib 30 mg, 40 mg, or 50 mg with selected endocrine therapy. Alisertib is an investigational oral Aurora A kinase inhibitor that disrupts mitotic spindle function and cell division. In a previous randomized phase 2 study of endocrine-resistant metastatic breast cancer, response rates were approximately 20% with alisertib alone or with fulvestrant; adding fulvestrant did not improve response rate or progression-free survival. Myelosuppression is a notable risk reported in alisertib studies.
Outcomes: Primary measures within each dose group are confirmed objective response rate, duration of response, disease control rate (including stable disease lasting at least 24 weeks), progression-free survival, overall survival, and treatment-emergent adverse events. These efficacy measures are also assessed in biomarker-defined subgroups. Outcomes are assessed for up to 48 months; adverse events are collected through 28 days after the last dose.
Burden on patient: Estimated moderate burden. Oral alisertib may limit treatment-related travel, but patients will need ongoing visits for safety monitoring and tumor assessments. Pharmacokinetic evaluation may require additional blood draws, and biomarker evaluation may require samples; the frequency of visits, scans, draws, and any biopsies is not specified. Potential myelosuppression may increase monitoring needs.
Last updated: Sep 2026
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.
Lisbon, 1400-038, Portugal
No email / No phone
Status: Recruiting
Lisbon, 1998-018, Portugal
No email / No phone
Status: Recruiting
Porto, 4200-072, Portugal
No email / No phone
Status: Recruiting
Lisbon, 1099-023, Portugal
No email / No phone
Status: Recruiting
Valencia, 46009, Spain
No email / No phone
Status: Recruiting
Valencia, 46010, Spain
No email / No phone
Status: Recruiting
Barcelona, 08036, Spain
No email / No phone
Status: Recruiting
Alicante, 03010, Spain
No email / No phone
Status: Recruiting
Granada, 18012, Spain
No email / No phone
Status: Recruiting
Cáceres, 10003, Spain
No email / No phone
Status: Recruiting
Lleida, 25198, Spain
No email / No phone
Status: Recruiting
Madrid, 28040, Spain
No email / No phone
Status: Recruiting
Huelva, 21005, Spain
No email / No phone
Status: Recruiting
Barcelona, 08035, Spain
No email / No phone
Status: Recruiting
Seville, 41013, Spain
No email / No phone
Status: Recruiting
Bilbao, 48013, Spain
No email / No phone
Status: Recruiting
Barakaldo, 48903, Spain
No email / No phone
Status: Recruiting
Jaén, 23007, Spain
No email / No phone
Status: Recruiting
Birmingham, Alabama, 34235, United States
No email / No phone
Status: Recruiting
Phoenix, Arizona, 85054, United States
No email / No phone
Status: Recruiting
Beverly Hills, California, 90211, United States
No email / No phone
Status: Recruiting
Irvine, California, 92618, United States
No email / No phone
Status: Recruiting
Los Angeles, California, 90017, United States
No email / No phone
Status: Recruiting
Fountain Valley, California, 92708, United States
No email / No phone
Status: Recruiting
Los Angeles, California, 90095, United States
No email / No phone
Status: Recruiting
San Francisco, California, 94158, United States
No email / No phone
Status: Recruiting
Aurora, Colorado, 80045, United States
No email / No phone
Status: Recruiting
Jacksonville, Florida, 32256, United States
No email / No phone
Status: Recruiting
Jacksonville, Florida, 32224, United States
No email / No phone
Status: Recruiting
Tampa, Florida, 33612, United States
No email / No phone
Status: Recruiting
Atlanta, Georgia, 30322, United States
No email / No phone
Status: Recruiting
Chicago, Illinois, 60637, United States
No email / No phone
Status: Recruiting
Chicago, Illinois, 60612, United States
No email / No phone
Status: Recruiting
Boston, Massachusetts, 02215, United States
No email / No phone
Status: Recruiting
Boston, Massachusetts, 02114, United States
No email / No phone
Status: Recruiting
Rochester, Minnesota, 55905, United States
No email / No phone
Status: Recruiting
Minneapolis, Minnesota, 55455, United States
No email / No phone
Status: Recruiting
Columbia, Missouri, 65201, United States
No email / No phone
Status: Recruiting
Springfield, Missouri, 65807, United States
No email / No phone
Status: Recruiting
Kansas City, Missouri, 64111, United States
No email / No phone
Status: Recruiting
St Louis, Missouri, 63110, United States
No email / No phone
Status: Recruiting
Reno, Nevada, 89511, United States
No email / No phone
Status: Recruiting
Rochester, New York, 14642, United States
No email / No phone
Status: Recruiting
Chapel Hill, North Carolina, 27514, United States
No email / No phone
Status: Recruiting
Maumee, Ohio, 43537, United States
No email / No phone
Status: Recruiting
Columbus, Ohio, 43212, United States
No email / No phone
Status: Recruiting
Horsham, Pennsylvania, 19044, United States
No email / No phone
Status: Recruiting
Philadelphia, Pennsylvania, 19104, United States
No email / No phone
Status: Recruiting
Pittsburgh, Pennsylvania, 15213, United States
No email / No phone
Status: Recruiting
Nashville, Tennessee, 37203, United States
No email / No phone
Status: Recruiting
Dallas, Texas, 75246, United States
No email / No phone
Status: Recruiting
Richmond, Virginia, 23229, United States
No email / No phone
Status: Recruiting
New Haven, Connecticut, 06520, United States
No email / No phone
Status: Withdrawn