Adj TC + Herceptin Early Stage Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Taxotere; Cytoxan; Herceptin
Intervention description: On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.; On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.; On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 493.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to find out what effects (good and bad)
      docetaxel/cyclophosphamide (brand names: Taxotere and Cytoxan, or TC) plus trastuzumab (brand
      name: Herceptin, or H) has HER2+ breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        A woman will be eligible for inclusion in this study if she meets all of the following
        criteria:

          -  Has HER2+ (IHC staining of 3+ [uniform, intense membrane staining of >30% of invasive
             tumor cells], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio
             [HER2 gene signals to chromosome 17 signals] of >2.2; patients with equivocal FISH
             ratio results 1.8-2.2 are also eligible if 3+ IHC) (Appendix IX); Stage I, IIA, IIB,
             or IIIA T1-3N1-3M0 disease. At the discretion of the Treating Physician, patients with
             4+ nodes with other factors such as patient choice, older age, preexisting cardiac
             disease with normal MUGA or ECHO may be enrolled into a separate subgroup.

          -  Has operable, histologically confirmed, invasive carcinoma of the breast.

          -  Has known ER and PR status

          -  Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix
             VII)

          -  Has had no prior chemotherapy unless it was given >5 years ago for breast cancer or
             other cancer

          -  Has an ECOG Performance Status (PS) 0-1

          -  Age >18 to <70 years old.

          -  Has laboratory values of: See protocol for specific details

          -  Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline
             phosphatase (ALP) within the ranges shown below. In determining eligibility the more
             abnormal of the 2 values (AST or ALT) should be used. See protocol for specific
             details

          -  Has complete surgical resection of the primary breast tumor: either lumpectomy or
             mastectomy with sentinel lymph node or axillary dissection.

          -  It has been <84 days since the date of definitive surgery, and there is adequate wound
             healing as determined by the Treating Physician

          -  Has no evidence of metastatic disease by physical examination and x-ray; appropriate
             scans as needed by each individual patient (eg, bone scan; abdominal, chest CT; PET or
             PET/CT; ultrasound; or MRI should indicate no evidence of metastatic disease.

          -  Has normal cardiac function as evidenced by a LVEF >50%, but must be within normal
             limits (WNL) by institutional standard, as determined by multiple gated acquisition
             (MUGA) scan. An echocardiogram (ECHO). The same modality must be used throughout the
             study to evaluate LVEF. Ejection fraction (EF) as determined by ECHO must be WNL by
             institutional standard.

          -  Has a negative serum pregnancy test within 7 calendar days prior to registration
             (female patients of childbearing potential [not surgically sterilized and between
             menarche and 1 year postmenopause]).

          -  If fertile, patient has agreed to use an acceptable method of birth control (barrier
             contraceptive) to avoid pregnancy for the duration of the study and for a period of 3
             months thereafter

          -  Has signed a Patient Informed Consent Form

          -  Has signed a Patient Authorization Form

        Exclusion Criteria:

        A woman will be excluded from this study if she meets any of the following criteria:

          -  Has any evidence of disease following complete surgical resection of the primary tumor
             and metastatic workup

          -  Has Stage IIIB breast cancer (T4 disease; ie, patients with fixed tumors, peau
             d'orange skin changes, skin ulcerations, or inflammatory changes).

          -  Has Stage IV breast cancer (M1 disease on TNM staging system)

          -  Had prior chemotherapy for breast cancer or other cancer within the last 5 years (no
             neoadjuvant chemotherapy in this study is permitted)

          -  Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate
             80

          -  Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New
             York Heart Association (NYHA) Class II or greater heart failure (see Appendix III),
             uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically
             significant pericardial disease, or electrocardiographic evidence of acute ischemic
             changes

          -  Has abnormal baseline MUGA (or ECHO) (<50%, or less than institutional LLN)

          -  Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy.
             Adjuvant hormonal therapy, if needed, may be given during radiation therapy and during
             treatment with trastuzumab after completion of chemotherapy.

          -  Is receiving concurrent investigational therapy or has received such therapy within
             the past 30 calendar days

          -  Has peripheral neuropathy >Grade 1

          -  Has a serious uncontrolled intercurrent medical or psychiatric illness, including
             serious viral (including clinically defined AIDS), bacterial or fungal infection; or
             history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the Treating
             Physician to be clinically significant, precluding informed consent

          -  Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is
             known to be HIV positive

          -  Has a history of other malignancy within the last 5 years (except cured basal cell
             carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the
             diagnosis or assessment of any of the study drugs

          -  Is an obese patient to whom the Treating Physician would not be comfortable
             administering full doses of study drugs as calculated by the BSA. Obese patients will
             be treated based on actual body weight. Obese patients treated with full doses based
             on actual BSA are eligible

          -  Is a pregnant or breastfeeding woman

          -  Is deemed unable to comply with requirements of study