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.
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.
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.
Single group
Neratinib
Drug120mg for 7 days; 160mg for 7 days ; 240mg for 7 days. 240 mg (up to a maximum of 24 weeks) orally daily\*.
Letrozole (L) or Anastrozole (A)
DrugL: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)\*
Trastuzumab
DrugAll 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.
Pathologic Complete Response (pCR)
pCR is defined as the lack of all signs of invasive cancer in the breast removed during surgery
Assess Adverse Events
Assess the adverse events of neratinib in combination with NSAI in subjects
Pathological Complete Response (pCR)
Estimate the pCR (ypT0/Tis ypN0) in the breast tissue and lymph nodes
Measure Residual Disease
Estimate residual disease in the breast tissue
Click on the lead sponsor to view all of their trials.
Ruth O'Regan
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
Puma Biotechnology, Inc.
Collaborator
University of Rochester
Collaborator
