Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Disseminated Tumor Cells
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Doxorubicin; Trastuzumab; Cyclophosphamide; Paclitaxel; Epirubicin; Docetaxel; Carboplatin; Fluorouracil
Intervention MeSH terms: Paclitaxel; Docetaxel; Cyclophosphamide; Carboplatin; Doxorubicin; Liposomal doxorubicin; Fluorouracil; Trastuzumab; Epirubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the efficacy of trastuzumab treatment in breast cancer patients
      with stage II-III human epidermal growth factor receptor 2 (HER2)-negative tumors and
      HER2-expressing bone marrow disseminated tumor cells (DTCs). Administering targeted
      trastuzumab therapy to these patients may result in the elimination of HER2 expressing
      disseminated tumor cells and improved disease free survival.
    

Eligibility criteria:

        Pre-Registration Inclusion Criteria:

          -  Histologically confirmed HER2-negative primary invasive ductal or invasive lobular
             breast carcinoma. For patients enrolling for neoadjuvant treatment, diagnosis must be
             clinical stage II or III; for patients enrolling for adjuvant treatment, diagnosis
             must be pathologic stage IIA to IIIC. Standard HER2 testing will be performed in the
             surgical specimen at Washington University according to the standard of care in the
             Department of Pathology. A HER2-negative primary breast cancer sample from a patient
             eligible for randomization should have a HER2 IHC score of 0 or 1+ Those patients with
             IHC score of 2+ should be HER2 FISH-negative in standard testing. Patient will have
             undergone staging studies including a CT of the chest/abdomen/pelvis and bone scan
             and/or PET scan either prior to the initiation of treatment or prior to entry into the
             trial. In addition, patients with non-metastatic, HER2-negative, recurrent tumors who
             need chemotherapy are eligible.

          -  Planning to receive best practice adjuvant or neoadjuvant chemotherapy according to
             institutional guidelines. Adjuvant tamoxifen or aromatase inhibitors treatment will be
             allowed for hormone receptor-positive patients. Patients who have failed neoadjuvant
             endocrine therapy will also be eligible.

          -  At least 18 years old.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

          -  Patient (or legally authorized representative) must be able to understand and willing
             to sign a written informed consent document.

        Pre-Registration Exclusion Criteria:

          -  Prior chemotherapy for this cancer (excluding initiation of best practice chemotherapy
             to be given as standard of care as described in this protocol, which may be initiated
             after the pre-registration bone marrow collection but before final confirmation of
             eligibility and randomization).

          -  Previous treatment with trastuzumab or any other Her2 targeted therapy.

          -  Presence of an uncontrolled intercurrent 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.

        Registration Inclusion Criteria

          -  Presence of bone marrow ERBB2 overexpressing DTCs at the time of diagnosis; bone
             marrow aspiration will be performed in consented patients to evaluate DTCs following
             pre-registration provided patients meet all eligibility criteria as described in this
             section.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

          -  Adequate cardiac function as demonstrated by LVEF of >55% performed no more than 4
             weeks prior to randomization.

          -  Normal organ and marrow function as defined below:

               -  leukocytes ≥3,000/mcL

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  hemoglobin ≥ 10 g/dL

               -  total bilirubin within institutional upper limits of normal unless related to
                  primary disease

               -  AST(SGOT)/ALT(SGPT) ≤2.0 X institutional upper limit of normal

               -  Creatinine ≤ 1.5 institutional upper limits of normal OR creatinine clearance ≥60
                  mL/min/1.73 m2 for patients with creatinine levels above institutional normal

          -  If a woman of childbearing potential, patient must use two forms of effective
             contraception for a minimum of 6 months following trastuzumab. Effective methods of
             birth control include use of established oral, injected, or implanted hormonal methods
             of birth control, IUD, IUS, and condoms.

        Registration Exclusion Criteria

          -  Evidence of distant metastasis present by CT scan, bone scan, or physical exam.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to trastuzumab.

          -  Prior chemotherapy for this cancer (excluding initiation of best practice chemotherapy
             to be given as standard of care described in this protocol, which may be initiated
             after the pre-registration bone marrow collection but before final confirmation of
             eligibility and randomization).

          -  History of other malignancy ≤ 5 years previous with the exception of basal cell or
             squamous cell carcinoma of the skin which were treated with local resection only or
             carcinoma in situ of the cervix.

          -  Pregnant or breastfeeding. Patient must have a negative serum pregnancy test ≤ 7 days
             from date of registration (if a woman of childbearing potential).

          -  Clinically important history of active liver disease, including viral or other
             hepatitis or cirrhosis.

          -  Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as
             less than the lower limit of normal for the institution despite adequate electrolyte
             supplementation.

          -  Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
             resulting in dyspnea at rest.