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Protocol No. NRGBR004

Principal Investigator Parkes, Amanda

Phase III

Age Group Adult

Scope National

Sponsor Type National

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

Objective This study is being done to answer the following question:
  • Can your breast cancer be stabilized and the time that you live with your breast cancer be lengthened by adding a new drug to the usual combination of drugs?
  • We are doing this study because we want to find out if this approach is better or worse than the usual approach for your breast cancer that is HER2-positive and has metastasized. The usual approach is defined as care most people get for breast cancer that is HER2-positive and has metastasized

  • Treatment
    Arm 1: Paclitaxel on Days 1, 8, 15, 22, 29, and 36 every 6 weeks for 4 cycles plus Trastuzumab + Pertuzumab Days 1 and 22 every 6 weeks until progression plus Placebo Days 1 and 22 every 6 weeks until progression or for 2 years
    Arm 2: Paclitaxel Days 1, 8, 15, 22, 29, and 36 every 6 weeks for 4 cycles plus Trastuzumab + Pertuzumab Days 1 and 22 every 6 weeks until progression plus Atezolizumab Days 1 and 22 every 6 weeks until progression or for 2 years

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

    Key Eligibility
  • 18 years of age or older
  • ECOG performance status 0-1
  • Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease confirmed as described by the protocol
  • Measurable disease based on RECIST 1.1
  • 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 according to ASCO/CAP guidelines
  • Tumor specimen obtained at the time of diagnosis used for HER2 testing must also have central testing for PD-L1 status
  • Tumor specimen obtained at the time of diagnosis used for HER2 and PD-L1 testing should also have central testing for ER and PgR according to current ASCO/CAP Guideline
  • Localized palliative radiation therapy is allowed for symptom management if completed greater than or equal to 14 days prior to randomization
  • Must have imaging of the chest/abdomen/pelvis, preferably with a CT scan, and a bone scan within 4 weeks prior to randomization
  • MRI of the brain (or contrast CT scan of the brain if patients are unable to undergo MRI) must be obtained in patients with symptoms suggesting possible central nervous system (CNS) metastatic disease
  • Adequate hematologic, hepatic and renal function as defined by the protocol
  • Serum TSH and morning cortisol must be obtained within 14 days prior to randomization to obtain a baseline value and be within normal limits
  • Patients not receiving anti-coagulant therapy must have PT and INR; 1.5 x ULN within 14 days prior to randomization. Patients receiving anti-coagulants should have a baseline INR assessed, but the value does not affect eligibility
  • LVEF must be greater than or equal to 55% regardless of the cardiac imaging facility's lower limit of normal
  • Can not be pregnant or breast feeding
    EXCLUSION
  • Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded exceptions as defined by the protocol
  • Leptomeningeal carcinomatosis
  • Metastatic disease limited to the CNS
  • History of systemic anti-cancer therapy (e.g., chemotherapy, targeted therapy) for MBC with the exception of administration of trastuzumab or lapatinib concurrently with radiation therapy for brain metastases
  • History of exposure to cumulative doses of doxorubicin greater than 360 mg per square meter of body-surface area or its equivalent
  • Prior treatment with mTOR inhibitors or CDK 4/6 inhibitors in combination with endocrine therapy for treatment of metastatic disease
  • Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Uncontrolled hypertension defined as sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg. (Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
  • Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens as defined by the protocol
  • Known to be HIV positive are eligible if they meet the criteria defined by the protocol
  • Active tuberculosis
  • Active hepatitis B virus, or hepatitis C virus
  • Treatment with systemic immunosuppressive medications as defined by the protocol
  • History or risk of autoimmune disease as defined by the protocol
  • Symptomatic peripheral ischemia
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis or greater than or equal to grade 1 pulmonary fibrosis, per the CTCAE v5.0, on screening chest CT scan

  • Applicable Disease Sites Breast

    Status Open

    Participating Institutions DN Greenwald Center; Oconomowoc Memorial Hospital, Waukesha Memorial; UW Cancer Center at ProHealth; UW Hospital and Clinics; UWCCC 1 South Park; Waukesha Memorial Hosp