Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab With or Without Estrogen Deprivation in Treating Patients With Hormone Receptor-Positive, HER2-Positive Operable or Locally Advanced Breast Cancer
Condition: HER2-Positive Breast Carcinoma; Hormone Receptor-Positive Breast Carcinoma; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7
MeSH terms: Carcinoma; Breast Neoplasms
Intervention: Aromatase Inhibition Therapy; Carboplatin; Cytology Specimen Collection Procedure; Docetaxel; Goserelin Acetate; Laboratory Biomarker Analysis; Pertuzumab; Quality-of-Life Assessment; Therapeutic Conventional Surgery; Trastuzumab; Whole Breast Irradiation
Intervention description: Given at the investigator's discretion; Given IV; Undergo 2 core biopsies; Given IV; Given SC; Correlative studies; Given IV; Ancillary studies; Undergo lumpectomy or mastectomy; Given IV; Undergo whole breast irradiation
Intervention MeSH terms: Carboplatin; Docetaxel; Trastuzumab; Pertuzumab; Goserelin; Trastuzumab biosimilar HLX02; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Aromatase Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 315.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies docetaxel, carboplatin, trastuzumab, and pertuzumab
      with estrogen deprivation to see how they work compared to docetaxel, carboplatin,
      trastuzumab, and pertuzumab without estrogen deprivation in treating patients with hormone
      receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer
      that is operable or has spread from where it started to nearby tissue or lymph nodes (locally
      advanced). Drugs used in chemotherapy, such as docetaxel, carboplatin, trastuzumab, and
      pertuzumab, 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 more than
      one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth
      of breast cancer cells. Hormone therapy using goserelin acetate and aromatase inhibition
      therapy may fight breast cancer by blocking the use of estrogen by the tumor cells. Radiation
      therapy uses high energy x rays to kill tumor cells. Giving combination chemotherapy and
      radiation therapy with or without hormone therapy may be an effective treatment for hormone
      receptor-positive, HER2-positive, operable or locally advanced breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients should have a life expectancy of at least 10 years, excluding their diagnosis
             of breast cancer; (comorbid conditions should be taken into consideration, but not the
             diagnosis of breast cancer)

          -  Women of reproductive potential must agree to use an effective non-hormonal method of
             contraception during study therapy (chemotherapy, trastuzumab, pertuzumab, and
             estrogen deprivation therapy) and for at least 7 months after the last dose of study
             therapy

          -  Submission of tumor samples is required for all patients; the local pathology
             department policy regarding release of tumor samples must be considered in the
             screening process; patients whose tumor samples are located in a pathology department
             that by policy will not submit any samples for research purposes should not be
             approached for participation in the B-52 trial

          -  The patient must have signed and dated an Institutional Review Board (IRB)-approved
             consent form that conforms to federal and institutional guidelines

          -  The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
             of 0 or 1

          -  Clinical staging for the primary tumor can be cT1c (must be 2.0 cm) or T2-T4 if
             clinically node negative; if the regional lymph nodes are cN1 and cytologically or
             histologically positive or if cN2-N3 with or without a biopsy, the primary breast
             tumor can be cT0-T4

          -  The diagnosis of invasive adenocarcinoma of the breast must have been made by core
             needle biopsy

          -  Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound,
             and/or magnetic resonance imaging [MRI]) within 6 weeks prior to randomization; if
             suspicious or abnormal, fine needle aspirate (FNA) or core biopsy is recommended, also
             within 6 weeks prior to randomization; findings of these evaluations will be used to
             determine the nodal status prior to randomization:

               -  Nodal status - negative

                    -  Imaging of the axilla is negative

                    -  Imaging is suspicious or abnormal but the FNA or core biopsy of the
                       questionable node(s) on imaging is negative

               -  Nodal status - positive

                    -  FNA or core biopsy of the node(s) is cytologically or histologically
                       suspicious or positive

                    -  Imaging is suspicious or abnormal but FNA or core biopsy was not performed

          -  Patients may be premenopausal or postmenopausal at the time of randomization; for
             study purposes, postmenopausal is defined as:

               -  Age 56 or older with no spontaneous menses for at least 12 months prior to study
                  entry; or

               -  Age 55 or younger with no spontaneous menses for at least 12 months prior to
                  study entry (e.g., spontaneous or secondary to hysterectomy) and with a
                  documented estradiol level in the postmenopausal range according to local
                  institutional/laboratory standard; or

               -  Documented bilateral oophorectomy

          -  The tumor must have been determined to be HER2-postive as follows:

               -  Immunohistochemistry (IHC) 3+ or

               -  In situ hybridization (ISH)-positive (defined by ratio of HER2 to circulating
                  endothelial progenitors [CEP]17 >= 2.0 or HER2 gene copy number >= 6 per nucleus)

          -  The tumor must have been determined to be estrogen receptor (ER) and/or progesterone
             (PgR) positive assessed by current American Society of Clinical Oncology
             (ASCO)/College of American Pathologist (CAP) guideline recommendations for hormone
             receptor testing; patients with >= 1% ER or PgR staining by IHC are considered
             positive

          -  Absolute neutrophil count (ANC) must be >= 1200/mm^3

          -  Platelet count must be >= 100,000/mm^3

          -  Hemoglobin must be >= 10 g/dL

          -  Total bilirubin must be =< upper limit of normal (ULN) for the lab unless the patient
             has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar
             syndrome involving slow conjugation of bilirubin

          -  Alkaline phosphatase must be =< 2.5 x ULN for the lab

          -  Aspartate aminotransferase (AST) must be =< 1.5 x ULN for the lab

          -  Alkaline phosphatase and AST may not both be > the ULN; for example, if the alkaline
             phosphatase is > the ULN but =< 2.5 x ULN, the AST must be =< the ULN; if the AST is >
             the ULN but =< 1.5 x ULN, the alkaline phosphatase must be =< ULN; Note: If alanine
             aminotransferase (ALT) is performed instead of AST (per institution's standard
             practice), the ALT value must be =< 1.5 x ULN; if both were performed, the AST must be
             =< 1.5 x ULN

          -  Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the
             study if liver imaging (computed tomography [CT], MRI, positron emission tomography
             [PET]-CT, or PET scan) performed within 6 weeks prior to randomization does not
             demonstrate metastatic disease and the requirements are met

          -  Patients with alkaline phosphatase that is > ULN but =< 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 6 weeks prior to randomization does not demonstrate metastatic
             disease

          -  Within 6 weeks prior to randomization, the most recent serum creatinine must be =< ULN
             or measured or calculated creatinine clearance must be > 60 mL/min

          -  Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days
             prior to randomization; (LVEF assessment performed by 2-dimensional [2-D]
             echocardiogram is preferred; however, multi gated acquisition scan [MUGA] scan may be
             substituted based on institutional preferences); the LVEF must be >= 50% regardless of
             the cardiac imaging facility's lower limit of normal; note: since the pre-entry LVEF
             serves as the baseline for comparing subsequent LVEF assessments, it is critical that
             this baseline study be an accurate assessment; if the baseline LVEF is > 65%, the
             investigator is encouraged to have the accuracy of the initial LVEF result confirmed
             and repeat the test if the accuracy is uncertain

        Exclusion Criteria:

          -  FNA alone to diagnose the breast cancer

          -  Excisional biopsy or lumpectomy performed prior to randomization

          -  Surgical axillary staging procedure prior to randomization; pre-neoadjuvant therapy
             sentinel node biopsy is not permitted

          -  Definitive clinical or radiologic evidence of metastatic disease; (chest imaging
             [mandatory for all patients] and other imaging [if required] must have been performed
             within 90 days prior to randomization)

          -  Synchronous bilateral invasive breast cancer

          -  Synchronous or previous contralateral invasive breast cancer; (patients with
             synchronous and/or previous contralateral ductal carcinoma in situ [DCIS] or lobular
             carcinoma in situ [LCIS] are eligible)

          -  Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS;
             (patients with synchronous or previous ipsilateral LCIS are eligible)

          -  Treatment including radiation therapy (RT), chemotherapy, targeted therapy, or
             endocrine therapy for the currently diagnosed breast cancer prior to randomization

          -  Previous endocrine therapy such as raloxifene or tamoxifen (or other selective
             estrogen receptor modulator [SERM]) or an aromatase inhibitor for any malignancy

          -  Previous therapy with anthracycline, taxanes, carboplatin, trastuzumab, or other HER2
             targeted therapies for any malignancy

          -  Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement
             therapy, etc. (these patients are eligible if this therapy is discontinued prior to
             randomization)

          -  History of non-breast malignancies (except for in situ cancers treated only by local
             excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior
             to randomization

          -  Cardiac disease (history of and/or active disease) that would preclude the use of the
             drugs included in the treatment regimens; this includes but is not confined to:

               -  Active cardiac disease:

                    -  Angina pectoris that requires the use of anti-anginal medication;

                    -  Ventricular arrhythmias except for benign premature ventricular
                       contractions;

                    -  Supraventricular and nodal arrhythmias requiring a pacemaker or not
                       controlled with medication;

                    -  Conduction abnormality requiring a pacemaker;

                    -  Valvular disease with documented compromise in cardiac function; and

                    -  Symptomatic pericarditis

               -  History of cardiac disease:

                    -  Myocardial infarction documented by elevated cardiac enzymes or persistent
                       regional wall abnormalities on assessment of left ventricular (LV) function;

                    -  History of documented congestive heart failure (CHF); and

                    -  Documented cardiomyopathy

          -  Uncontrolled hypertension defined as sustained systolic blood pressure (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)

          -  Active hepatitis B or hepatitis C with abnormal liver function tests

          -  Intrinsic lung disease resulting in dyspnea

          -  Poorly controlled diabetes mellitus

          -  Active infection or chronic infection requiring chronic suppressive antibiotics

          -  Patients known to be human immunodeficiency virus (HIV) positive with a baseline
             cluster of differentiation (CD)4 count of < 250 cells/mm^3 or have a history of
             acquired immune deficiency syndrome (AIDS) indicator conditions; patients taking
             anti-retroviral therapy that may have a potential overlapping toxicity with the study
             therapy are not eligible

          -  Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral
             sensory neuropathy) >= grade 2, per the Common Terminology Criteria for Adverse Events
             version 4.0 (CTCAE v4.0)

          -  Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel,
             or other disease significantly affecting gastrointestinal function

          -  Other non-malignant systemic disease that would preclude treatment with any of the
             treatment regimens or would prevent required follow-up

          -  Conditions that would prohibit administration of corticosteroids

          -  Chronic daily treatment with corticosteroids with a dose of >= 10 mg/day
             methylprednisolone equivalent (excluding inhaled steroids)

          -  Known hypersensitivity to any of the study drugs or any of the ingredients or
             excipients of these drugs (e.g., polysorbate 80), including sensitivity to benzyl
             alcohol

          -  Pregnancy or lactation at the time of study entry; (note: pregnancy testing must be
             performed within 2 weeks prior to randomization according to institutional standards
             for women of childbearing potential)

          -  Psychiatric or addictive disorders or other conditions that, in the opinion of the
             investigator, would preclude the patient from meeting the study requirements

          -  Use of any investigational product within 30 days prior to randomization