Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in HER2+ Breast Cancer Patients

Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients With Operable or Locally Advanced/Inflammatory HER2-positive Breast Cancer (ImmunHER)

Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients with Operable or Locally Advanced /Inflammatory HER2-positive Breast Cancer (ImmunHER)

Women with histologically confirmed HER2-positive breast cancer with locally advanced, inflammatory,or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.

Inclusion Criteria:

• Previously untreated, infiltrating primary breast cancer with locally advanced, inflammatory, or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.
• HER2 positivity (either immunohistochemistry 3+ or fluorescent in situ hybridization amplification).
• Age 18 or older.
• Eastern Cooperative Oncology Group performance status of 0 to 1.
• Availability of tumor tissue for biologic and molecular examination before starting primary treatment.
• Left ventricular ejection fraction within the institutional range of normal.
• Normal organ and marrow function.
• Adequate contraception methods for women of childbearing potential.
• Prior diagnosis of cancer is allowed as long as patient is free of disease and has been off treatment for the prior malignancy for a minimal interval of 3 years.
• Written informed consent.

Exclusion Criteria:

• Either stage I or IV breast cancer.
• Prior trastuzumab or pertuzumab.
• Any prior chemotherapy.
• Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
• Undergone major surgery (e.g., intrathoracic, intra-abdominal or intra-pelvic) 4 weeks prior to starting study drug or who have not recovered from side effects of such surgery.
• Breast radiotherapy prior to starting study.
• Known hypersensitivity to the investigational drugs or any of their excipients.
• Evidence of any disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an GOIRC-01-2016 ImmunHER Protocol Version 1.0, 11 April 2016 Page 6 of 140 investigational drug, or puts the patient at high risk for treatment-related complications.
• Moderate/severe hepatic impairment (Child- Pugh B/C).
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Concurrent malignancy or malignancy within 3 years prior to study enrollment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or insitu carcinoma of the uterine cervix.
• Pregnancy or breastfeeding (breast feeding should be discontinued to be enrolled in the study).
• Women of childbearing potential that refusal to adopt adequate contraceptive measures.
• Unwilling or unable to comply with the protocol. -