Trastuzumab, Pertuzumab, and Combination Chemotherapy in Treating Patients with Locally Advanced, Resectable, or Inflammatory Her2 Positive Breast Cancer

Status: Active

Description

This phase II trial studies how well trastuzumab, pertuzumab, and combination chemotherapy work in treating patients with Her2 positive breast cancer that has spread from where it started to nearby tissue or lymph nodes, can be removed by surgery, or is inflammatory. Immunotherapy with monoclonal antibodies, such as trastuzumab and pertuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, docetaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trastuzumab, pertuzumab, and combination chemotherapy may work better in treating patients with breast cancer.

Eligibility Criteria

Inclusion Criteria

  • The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Eligible tumors must meet one of the following criteria: * Operable (T1c, T2-3, N0-1, M0) * Locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0) * Inflammatory breast cancer (T4d, any N, M0)
  • Staging evaluation: * History and physical exam, blood cell count (cbc), chemistry profile * Computed tomography (CT) chest/abdomen/pelvis and a bone scan or positron emission tomography (PET)/CT as needed
  • Diagnosis of invasive adenocarcinoma made by core needle biopsy
  • Breast cancer determined to be: * Confirmed HER2-positive: (American Society of Clinical Oncology [ASCO] College of American Pathologists [CAP] guidelines, 10/7/2013) ** Immunohistochemistry (IHC) 3+ based on circumferential membrane staining that is complete, intense ** In situ hybridization (ISH) positive based on: ** Single probe average HER2 copy number >= 6 signals/cell ** Dual probe HER2/CEP 17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell ** Dual probe HER2/CEP 17 ratio >= 2.0, with an average HER2 copy number of < 4.0 signals/cell ** Dual probe HER2/CEP17 ratio < 2.0 with the average HER2 copy number of >= 6.0 signals/cell * Any estrogen receptor (ER) or progesterone receptor (PR) receptor status
  • LVEF assessment by echocardiogram within 30 days of initiation; ejection fraction (EF) of >= 55% considered normal
  • Normal troponin I level at baseline
  • Absolute neutrophil count (ANC) greater than or equal to 1500/mm^3
  • Platelet count greater than or equal to 100,000/mm^3
  • Hemoglobin greater than or equal to 10 g/dL
  • Serum creatinine less than or equal 2.5 mg/100 ml
  • Total bilirubin must be less than or equal to 1.5 x the upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation greater than the ULN to 1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin
  • Alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab
  • Aspartate aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab
  • Both alkaline phosphatase and AST may not both be greater than the ULN
  • Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, magnetic resonance imaging [MRI], PET-CT or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the requirements are met as above
  • Patients with alkaline phosphatase that is > ULN but less than or equal to 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease

Exclusion Criteria

  • Patients with a history of decompensated congestive heart failure or an EF < 55% will be excluded
  • Cardiac disease that would preclude the use of the drugs included in the above regimens. This includes but is not confined to: * Active cardiac disease: ** Angina pectoris requiring the use of anti-anginal medication ** Ventricular arrhythmias except for benign premature ventricular contractions controlled by medication ** Conduction abnormality requiring a pacemaker ** Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and ** Clinically significant valvular disease ** Symptomatic pericarditis ** Pulmonary hypertension * History of cardiac disease: ** Myocardial infarction ** Congestive heart failure; or ** Cardiomyopathy
  • Definitive clinical or radiologic evidence of metastatic disease or bilateral breast cancer
  • History of non-breast malignancies (except for in-situ cancer treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
  • Previous therapy with anthracyclines, taxanes, or trastuzumab for any malignancy
  • Pregnant or refusing to use contraception

Locations & Contacts

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Contact: Aarti S. Bhardwaj
Phone: 212-824-8585
Email: aarti.bhardwaj@mountsinai.org
Mount Sinai Chelsea
Status: Active
Contact: Paula Klein
Phone: 212-604-6021
Mount Sinai West
Status: Active
Contact: Anupama Goel
Phone: 212-523-6769

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determination of pathologic complete response (pCR) rates, defined by the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0 ypN0 in the current American Joint Committee on Cancer [AJCC] system).

SECONDARY OBJECTIVES:

I. Determination of cardiac toxicity as measured by: composite of left ventricular ejection fraction (LVEF), longitudinal strain and troponin.

II. Breast conservation rates.

III. Overall survival.

OUTLINE: Patients are randomized to 1 of 2 regimens.

REGIMEN I: Patients receive doxorubicin intravenously (IV) and cyclophosphamide IV on day 1, and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15, trastuzumab IV on day 1, and pertuzumab IV every 3 weeks. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV on day 1. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity.

REGIMEN II: Patients receive docetaxel IV, carboplatin IV, trastuzumab IV, and pertuzumab IV on day 1, and pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV on day 1. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 1 year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Icahn School of Medicine at Mount Sinai

Principal Investigator
Aarti S. Bhardwaj

Trial IDs

Primary ID 17-1585
Secondary IDs NCI-2018-03595
Clinicaltrials.gov ID NCT03329378