Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Carcinoma

Carcinoma, Lobular

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Amino Acids

Neratinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive standard of care endocrine therapy over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

Patients receive standard of care endocrine therapy and neratinib PO over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then continue endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

Endocrine Therapy

Biopsy of breast

Biospecimen Collection

Mammogram

Undergo breast Magnetic Resonance Imaging

Magnetic Resonance Imaging

Breast Surgery

Ultrasound

Vanderbilt-Ingram Services for Timely Access

Kevin Kalinsky, MD

Adam Brufsky, MD

Vanderbilt-Ingram Service for Timely Access

Laura Kennedy, MD, PhD

Carlos Arteaga, MD

Bora Lim, MD

This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving neratinib in addition to normal therapy may work better in treating cancer than the endocrine therapy patients would normally receive.

PRIMARY OBJECTIVE:

I. Determine efficacy of neoadjuvant neratinib in combination with endocrine therapy.

SECONDARY OBJECTIVES:

I. Determine additional efficacy outcomes of neoadjuvant neratinib in combination with endocrine therapy.

II. Compare the safety and tolerability of neratinib plus endocrine therapy.

CORRELATIVE OBJECTIVE:

I. Establish HER2-mutant invasive lobular carcinoma (ILC) organoids.

OUTLINE: Patients are randomized to 1 of 2 treatments.

TREATMENT A: Patients receive standard of care endocrine therapy over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then endocrine therapy and neratinib orally (PO) daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast magnetic resonance imaging (MRI) prior to surgery.

TREATMENT B: Patients receive standard of care endocrine therapy and neratinib PO over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then continue endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

After completion of study treatment, patients are followed up for 4 weeks after study drugs interruption.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers	NCT05919108	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Invasive Breast...	Endocrine Thera... Biopsy of breas... Neratinib Biospecimen Col... Mammogram Magnetic Resona... Breast Surgery Ultrasound	18 Years -	Vanderbilt-Ingram Cancer Center
Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers	NCT05919108	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Invasive Breast...	Endocrine Thera... Biopsy of breas... Neratinib Biospecimen Col... Mammogram Magnetic Resona... Breast Surgery Ultrasound	18 Years -	Vanderbilt-Ingram Cancer Center

Spots Global Cancer Trial Database for anatomic stage ii breast cancer