Pre-operative Neratinib and Endocrine Therapy for HER2-Positive Breast Cancer
This study is looking at a new way to treat ER-positive, HER2-positive breast cancer before surgery. Participants will receive a combination of drugs: neratinib, an aromatase inhibitor (either letrozole or anastrozole), and trastuzumab. The treatment will last for 24 weeks before surgery, with an initial 3 weeks where you might receive neratinib alone, an aromatase inhibitor alone, or both. A breast biopsy will be done before week 4 of treatment. After surgery, you'll receive standard care. Researchers want to see how well this treatment shrinks the tumor before surgery. To join, you must be at least 18 years old and postmenopausal. The study plans to enroll 30 participants.
- Study design
- This is an interventional study, meaning participants will receive specific treatments. It plans to enroll 30 participants.
- What's involved
- You would receive neratinib, an aromatase inhibitor (letrozole or anastrozole), and trastuzumab for 24 weeks before surgery. A breast biopsy will be performed before Day 1 of week 4 of treatment.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint, pathologic complete response, is measured at 24 weeks. After surgery, patients will receive standard of care, but the duration of follow-up for the study is not specified.
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NCT04886531
Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers
Recruiting
PHASE2Ages 18+InterventionalTreatmentRuth O'ReganInvestigator-initiated
~30 participants
Updated 2026-04-08 on ClinicalTrials.gov
What's tested:NeratinibLetrozole (L) or Anastrozole (A)Trastuzumab
At a glance
Recruiting sites
4 of 4 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Pathologic Complete Response (pCR)
Measured over 24 weeks
Conditions
Where it's being run
4 sites across 4 statesIllinois1
New York1
Pennsylvania1
Wisconsin1
Study leadership
- Ruth O'Regan, MD · PRINCIPAL_INVESTIGATOR · University of Rochester
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral oophorectomy, Age ≥ 60 years, or Age \< 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an estradiol level in postmenopausal ranges per local reference range.
ECOG Performance Status of 0-2 within 28 days prior to registration.
Anatomic, clinical stage I-III, invasive breast cancer, greater than 10mm
HER2-positive (by the most recent ASCO-CAP criteria)
ER positive (≥ 10%). NOTE: There is no requirement for PR status; PR positive or negative allowed.
Resectable breast cancer in which pre-operative therapy is appropriate (T \> 10mm and/or node-positive).
Archival tissue from the diagnostic pre-treatment biopsy is required. This sample should be identified at screening and shipped by Week 4. If archival tissue is not available, the subject is not eligible for the study.
Agreeable to repeat breast biopsy at 3 weeks after initiation of treatment.
Candidate for either letrozole or anastrozole, as determined by the treating physician
Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to the study treatment.
Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
Hematological
Platelet count ≥100,000/uL
Absolute Neutrophil Count (ANC) ≥1500/uL
Hemoglobin (Hgb) ≥10 g/dL
Renal
Calculated creatinine clearance: CrCl ≥30 mL/min using the Cockcroft-Gault formula
Hepatic
Bilirubin ≤1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) ≤ 2.5 × ULN
Alanine aminotransferase (ALT) ≤ 2.5 × ULN
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
For patients with known serologic evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Exclusion
Locally advanced or inflammatory breast cancer. NOTE: Locally advanced is defined as Stage IIIC or greater.
Evidence of metastatic disease. Systemic imaging is not required.
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: exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
Active infection requiring systemic therapy.
Requirement for use of a moderate or strong CYP3A4 inhibitor or inducer during the study (see protocol).
Treatment with any investigational drug within 14 days prior to registration or within 5 half-lives of the investigational product, whichever is longer.
Subject has had major surgery within 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery).
Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) or significantly impair the ability to swallow capsules/tablets.
Known history of myelodysplastic syndrome or acute myeloid leukemia.
Subjects with any of the following conditions:
History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days prior to registration.
Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to registration.
History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to registration.
Symptomatic congestive heart failure (New York Heart Association III-IV) or documented current cardiomyopathy with left ventricular ejection fraction (LVEF) \<50%.
Clinically significant cardiac ventricular arrhythmias (e.g. sustained ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker is in place.
Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
Any concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study or compromise compliance with the protocol.
What this trial measures
- Pathologic Complete Response (pCR)24 weeks
pCR is defined as the lack of all signs of invasive cancer in the breast removed during surgery