Breast Cancer NRG-BR004

A Randomized, Double-Blind, Phase III Trial of Paclitaxel/Trastuzumab/Pertuzumab with Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer.

This randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body (metastatic). Chemotherapy drugs, such as paclitaxel, 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. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may interfere with the ability of cancer cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells.

Eligibility Criteria:

  • Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease confirmed as described below. Eligible patients include those with either:
  • De novo metastatic disease without prior history of HER2-positive breast cancer:
    • Diagnosis should have been made from a biopsy of a metastatic disease site, but biopsy from the breast primary or involved regional lymph nodes is acceptable if biopsy of the metastatic sites was thought to carry excessive risk for the patient.
  • Locally recurrent or metastatic disease following prior therapy for early breast cancer: − Diagnosis must have been made from the biopsy of the locally recurrent or metastatic disease.
    • There must be an interval of ≥ 6 months between completion of neoadjuvant/adjuvant HER2-targeted therapy and documentation of locally recurrent or metastatic HER2- positive disease by biopsy
  • The tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been determined to be HER2-positive based on central testing. Sites can send biopsy specimens for central testing which have been determined to be HER2-positive or initially equivocal by either IHC or ISH on local testing.
  • No Known leptomeningeal carcinomatosis.
  • No Patients with metastatic disease limited to the CNS.
  • No History of exposure to cumulative doses of doxorubicin greater than 360 mg per square meter of body-surface area or its equivalent.

This study is for patients age 18 and older.

Available at: Hartford Hospital, Hospital of Central Connecticut, Midstate Medical Center, William Backus Hospital

Cancer Clinical Research Office