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

Not Recruiting

Trial ID: NCT02003209


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.

Official Title

A Randomized Phase III Trial Evaluating Pathologic Complete Response Rates in Patients With Hormone Receptor-Positive, HER2-Positive, Large Operable and Locally Advanced Breast Cancer Treated With Neoadjuvant Therapy of Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP) With or Without Estrogen Deprivation

Stanford Investigator(s)

Irene Wapnir, MD
Irene Wapnir, MD

Professor of Surgery (General Surgery)

Melinda L. Telli, M.D.
Melinda L. Telli, M.D.

Professor of Medicine (Oncology)


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

   - 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

   - 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

   - 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

   - 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

         - 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

   - 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


drug: docetaxel

drug: carboplatin

biological: trastuzumab

biological: pertuzumab

drug: goserelin acetate

procedure: therapeutic conventional surgery

radiation: whole breast irradiation

other: laboratory biomarker analysis

drug: aromatase inhibition therapy

other: quality-of-life assessment

other: Cytology Specimen Collection Procedure

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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