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Neratinib for HER2-Mutated Lobular Breast Cancer

This study is testing a medication called neratinib for people with stage I-III HER2-mutated lobular breast cancer. Neratinib is a kinase inhibitor, which means it works by blocking a protein that helps cancer cells grow. The study aims to see if adding neratinib to the usual hormone therapy (endocrine therapy) works better than hormone therapy alone before surgery. To join, you must be at least 18 years old and have a new diagnosis of stage I-III hormone receptor-positive invasive lobular breast cancer. The main goal is to measure a score that helps predict how well the treatment works over time. The current status of this study is unclear.

Study design
This interventional study plans to enroll 30 participants. It compares two treatment groups: one receiving standard hormone therapy followed by hormone therapy plus neratinib, and another receiving hormone therapy plus neratinib from the start.
What's involved
You would undergo breast biopsies, blood draws, mammograms, and take neratinib by mouth daily for about 20 weeks. You would also have surgery after this treatment period.
Compensation
Not stated in the trial record.
Follow-up
The primary outcome of the study is measured for up to 5 years after treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05919108

Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers

Recruiting
PHASE2Ages 18+InterventionalTreatment
Vanderbilt-Ingram Cancer Center
~30 participants
Updated 2026-08-19 on ClinicalTrials.gov
What's tested:Endocrine TherapyBiopsy of breastNeratinibBiospecimen CollectionMammogramMagnetic Resonance Imaging

At a glance

Recruiting sites
2 of 5 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Preoperative endocrine prognostic index score
Measured over Up to 5 years

Conditions

Anatomic Stage I Breast Cancer
Anatomic Stage II Breast Cancer
Anatomic Stage III Breast Cancer
Invasive Breast Lobular Carcinoma

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NCT05919108

Where you'd take part

This study runs at 5 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • University of Texas, Southwestern

    Dallas, Texasstudy coordinator listed

    Recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennesseestudy coordinator listed

    Recruiting

  • Baylor College of Medicine

    Houston, Texasno site contact published

    Not yet recruiting

  • Emory University/ Winship Cancer Institute

    Atlanta, Georgiano site contact published

    Not yet recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvaniano site contact published

    Not yet recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Laura Kennedy, MD, PhD · PRINCIPAL_INVESTIGATOR · Vanderbilt University/Ingram Cancer Center

Who to contact

Vanderbilt-Ingram Services for Timely Access
[email protected]
800-811-8480
Email the study team

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Eligibility criteria

Inclusion

Subjects aged 18 years or older at signing of informed consent.
New diagnosis of clinical stage I-III HR+ histologically-proven (i.e. absent or decreased e-cadherin expression) invasive lobular carcinoma
Synchronous breast tumors are permitted as long as the synchronous tumor is ER+ and HER2-negative.
ER+ disease defined as ≥1% estrogen receptor (ER) positive consistent with current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society of Medical Oncology (ESMO) guidelines)
At the time of screening, histologically confirmed cancers in patients with previously documented activating HER2 mutation (see Appendix A) confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory.
Archival tissue availability (if not available a fresh tumor biopsy will be required) and subject must agree to submission of sample for central testing
Minimum tumor size of ≥1.5 cm by US, mammogram, MRI imaging, or clinical breast exam
ECOG performance status 0 or 1
Patients must have adequate hematologic, hepatic, and renal function. All laboratory tests must be obtained within 1 month of study entry. This includes:
Estimated glomerular filtration rate of ≥50 mL/min
Albumin ≥ 2.5 g/dL
ANC ≥1500/mm\^3
Platelet count ≥100,000/mm\^3
HgB ≥ 9 g/dL
Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
AST and ALT ≤ 3 x ULN
Pre-, peri-, or post-menopausal, confirmed by history or laboratory testing as needed
Diagnostic biopsy tissue availability with sufficient tumor to permit NGS (if not available, a fresh biopsy will be required)
No prior treatment for current diagnosis of breast cancer
For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and/or uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment. Hormone based oral contraceptives are not allowed on study. Postmenopausal is defined as:
Age ≥ 55 years
Age ≤ 55 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range. Female participants of childbearing potential are eligible to participate if they agree to use a highly effective method of contraception that has a low user dependency consistently and correctly.

Exclusion

Evidence of distant metastatic disease
Synchronous breast cancer that is estrogen receptor negative OR HER2-amplified OR requires treatment with neoadjuvant chemotherapy per the judgement of the treating physician
Patients harboring ineligible somatic HER2 mutations, such as those that are subclonal in nature or those resulting in the expression of truncated proteins including alterations that result in premature stop codon or a change in reading frame (ie, frame shift mutations).
Prior endocrine therapy for breast cancer within the last 2 years
Women who are pregnant, are planning to become pregnant, or are breast-feeding
Any investigational treatment for the current diagnosis of breast cancer
HER2 amplification by FISH (HER2:CEP17 ratio \>2.0) or IHC (HER2 (3+)
Hepatic function impairment as defined by AST or ALT \> 3x ULN OR total serum bilirubin \> 1.5 (in patients with known Gilbert syndrome, a total bilirubin of \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN)
Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 4.0 \[CTCAE version 4.0\] diarrhea of any etiology at baseline.
Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investigator's judgment, make the patient inappropriate for this study.
Known hypersensitivity to any component of the investigational product, required combination therapy, or loperamide.
Unable or unwilling to swallow tablets.
Unable or unwilling to complete study procedures such as research biopsies or imaging
Any medical condition that in the judgement of the co-investigator would impair the patient's ability to complete the planned study therapy

What this trial measures

  • Preoperative endocrine prognostic index scoreUp to 5 years