Targeting Aurora A Kinase to Overcome Treatment Resistance in Advanced HR+/HER2+ Breast Cancer

NCT07706179 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 2026-0872UW26020Protocol Version 5/22/26UWMSN | SMPH | DOM-Administrat
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if alisertib in addition to usual care works to treat HR+/HER2+ breast cancer. The main questions it aims to answer are:

• Does alisertib stop the communication between HR and HER2?
• Are there genetic markers that predict how well someone's cancer will respond to alisertib? Participants will receive alisertib in addition to their usual care.

Conditions

HR+/HER2+ Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Clinical benefit defined as partial tumor response (PR)

  As defined by RECIST 1.1. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  12 weeks

• Clinical benefit defined as complete tumor response (CR)

  As defined by RECIST 1.1 Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm

  12 weeks

• Clinical benefit defined as decline in circulating tumor DNA (ctDNA)

  Clinical benefit is defined as a decline in ctDNA by \>50%.

  12 weeks

Secondary Outcomes (2)

• Evaluate safety of adding alisertib to usual care by assessing adverse events

  12 weeks

• BRD8 signature expression

  12 weeks

Study Arms (1)

Alisertib plus standard of care

EXPERIMENTAL

Participants receive alisertib in addition to usual care

Drug: Alisertib

Interventions

Alisertib DRUG

Alisertib 40mg on days 1-7 of 21-day cycles for 4 cycles

Alisertib plus standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years at the time of consent.
• ECOG performance status \</=2 (Karnofsky \>/=60%).
• Metastatic HR+/HER2+ breast cancer (estrogen receptor (ER) and/or progesterone receptor (PR) ≥1%, HER2 3+ by immunohistochemistry (IHC) or amplified by in situ hybridization (ISH).
• Prior standard induction treatment with chemotherapy + trastuzumab + pertuzumab (HP) or fam-trastuzumab deruxtecan (T-DXd) and have completed a minimum of 4 cycles without progressive disease.
• Planned to start or are receiving endocrine therapy + HER2-directed (HP or pertuzumab/trastuzumab/hyaluronidase-zzxf (PHESGO®)) therapy.
• Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration.
• Left ventricular ejection fraction ≥ 50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 6 weeks prior to the study treatment.
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors volume 1.1 (RECIST 1.1) or evaluable disease with circulating tumor DNA (ctDNA) that is detectible. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
• Willingness to receive growth factor injections for neutropenia prophylaxis. Only patients without any grade 3 or higher neutropenia during induction chemotherapy or T-DXd will be permitted to proceed without prophylactic growth factor support. If the enrolled patients in this trial develop high grade or prolonged neutropenia, the addition of growth factor will be required.

You may not qualify if:

• Active infection requiring systemic therapy.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
• Treatment with any investigational drug within 14 days prior to registration, or within 5 half-lives of the investigational product, whichever is longer.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

MLN 8237

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kari Wisinski, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: July 15, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)