Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers

NCT04886531 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN BRE17-141
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of care HER2-directed and endocrine therapy at the treating physician's discretion.

Conditions

HER2-positive Breast Cancer; ER Positive Breast Cancer; PR-Positive Breast Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR)

  pCR is defined as the lack of all signs of invasive cancer in the breast removed during surgery

  24 weeks

Secondary Outcomes (3)

• Assess Adverse Events

  24 weeks

• Pathological Complete Response (pCR)

  24 weeks

• Measure Residual Disease

  24 weeks

Study Arms (1)

A

EXPERIMENTAL

Weeks 1-3\* patients receive either (a) Neratinib, (b) Letrozole or Anastrozole or (c) Neratinib + Letrozole or Anastrozole Weeks 4-24 patients receive Neratinib + Letrozole or Anastrozole and Trastuzumab \*Starting drug intervention varies for the first 3 weeks depending on arms: a, b, and c by randomization.

Drug: Neratinib; Drug: Letrozole (L) or Anastrozole (A); Drug: Trastuzumab

Interventions

Trastuzumab DRUG

All Arms 8mg/kg loading dose followed by 6mg/kg every 3 weeks administered every 3 weeks by IV starting wk 4. Trastuzumab biosimilars may be used per institutional guidelines.

Also known as: Herceptin

A

Neratinib DRUG

120mg for 7 days; 160mg for 7 days ; 240mg for 7 days. 240 mg (up to a maximum of 24 weeks) orally daily\*.

Also known as: Nerlynx

A

Letrozole (L) or Anastrozole (A) DRUG

L: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)\*

Also known as: Femara, Arimidex

A

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• 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%.

Sponsors & Collaborators

• Ruth O'Regan: lead
• Puma Biotechnology, Inc.: collaborator
• University of Rochester: collaborator

Study Sites (4)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

neratinib; Letrozole; Anastrozole; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ruth O'Regan, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth O'Regan, MD

CONTACT

608-265-9701; ruth_oregan@urmc.rochester.edu

Amber Ryba

CONTACT

317-634-5842; aryba@hoosiercancer.org

Study Design

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

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 14, 2021
• Study Start: July 21, 2022
• Primary Completion (Estimated): June 22, 2026
• Study Completion (Estimated): July 21, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)