NCT05919108

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

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

Interventions

Type	Name	Description
PROCEDURE	Endocrine Therapy	Undergo endocrine therapy
PROCEDURE	Biopsy of breast	Undergo breast biopsy
DRUG	Neratinib	Taken by mouth
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Mammogram	Undergo Mammogram
PROCEDURE	Magnetic Resonance Imaging	Undergo breast Magnetic Resonance Imaging
PROCEDURE	Breast Surgery	Undergo Breast Surgery
PROCEDURE	Ultrasound	Undergo Ultrasound

Timeline

• Start date: 2024-05-30
• Primary completion: 2030-04-30
• Completion: 2031-04-30
• First posted: 2023-06-26
• Last updated: 2025-09-09

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study