Doxorubicin and Cyclophosphamide Followed By Trastuzumab, Paclitaxel, and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery

This is an interventional treatment trial for Breast Cancer focused on measuring cardiac toxicity, male breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer Read More

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of early-stage breast cancer

  • HER2 positive by immunohistochemistry (IHC) (3+) or fluorescent in situ hybridization (FISH)

    • Ductal carcinoma in situ (DCIS) components should not be counted in the determination of degree of IHC staining or FISH amplification

• No locally advanced tumors (i.e., T4) at diagnosis, including the following:

  • Tumors fixed to chest wall
  • Peau d'orange
  • Skin ulcerations or nodules
  • Clinical inflammatory changes (e.g., diffuse brawny cutaneous induration with an erysipeloid edge)

• Has undergone mastectomy or lumpectomy with axillary node or sentinel node dissection within the past 84 days

  • Patients who have undergone a mastectomy must meet the following criteria:

    • No evidence of gross or microscopic tumor (i.e., invasive DCIS) at the surgical resection margins noted in final surgery or pathology reports

      • Patients with close margins are eligible
    • Radiation therapy is required for 4 or more positive lymph nodes and must be started after completion of chemotherapy

  • Patients who have undergone a lumpectomy with axillary node or sentinel node dissection must meet the following criteria:

    • No evidence of invasive cancer or DCIS at the surgical resection margins
    • No gross residual adenopathy
    • Planning to undergo radiation therapy to the breast with or without regional lymphatics after completion of chemotherapy

• No active hepatic or biliary disease

  • Patients with liver metastases, stable chronic liver disease, Gilbert's syndrome, or asymptomatic gallstones are eligible

• Hormone receptor status:

  • Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS:

• Male or female
• Menopausal status not specified
• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10.0 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• LVEF ≥ 50% by MUGA scan or echocardiogram
• Able to complete questionnaire(s) by themselves or with assistance
• Able and willing to provide blood and tissue samples
• No known sensitivity to benzyl alcohol
• No sensory neuropathy ≥ grade 2

• No active cardiac disease, including any of the following:

  • Myocardial infarction within the past 6 months
  • Prior or concurrent congestive heart failure
  • Prior or concurrent arrhythmia or cardiac valvular disease requiring medications or that is clinically significant
  • Uncontrolled hypertension, defined as diastolic blood pressure (BP) >100 mm Hg or systolic BP > 200 mm Hg on 2 separate occasions ≥ 14 days apart
  • Clinically significant pericardial effusion
  • Prior or concurrent uncontrolled or symptomatic angina
  • Other cardiac condition that, in the opinion of the treating physician, would put the patient at hazardous risk
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition as lapatinib ditosylate

• No uncontrolled intercurrent illness including, but not limited to, the following:

  • Ongoing or active infection
  • Psychiatric illness or social situations that would preclude study compliance

• Able to swallow and retain oral medication

  • No history of gastrointestinal (GI) disease resulting in an inability to take oral medication, including any of the following:

    • Malabsorption syndrome
    • Requirement for IV alimentation
    • Prior surgical procedures affecting absorption
    • Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer
• No primary breast radiation therapy as part of breast-conserving treatment
• No prior anthracycline or taxane therapy for any malignancy
• No prior epidermal growth factor receptor-targeting therapies (e.g., gefitinib, cetuximab, erlotinib hydrochloride, rituximab, trastuzumab [Herceptin®], lapatinib ditosylate, panitumumab, or nimotuzumab)

• At least 14 days since prior and no concurrent CYP3A4 inducers, including the following:

  • Rifamycin-class antibiotics (e.g., rifampin, rifabutin, or rifapentine)
  • Anticonvulsants (e.g., phenytoin, carbamazepine, or barbiturates [e.g., phenobarbital])
  • Antiretrovirals (e.g., efavirenz or nevirapine)

  • Glucocorticoids (e.g., oral cortisone, hydrocortisone, prednisone, methylprednisolone, or dexamethasone)

    • Daily oral dexamethasone ≤ 1.5 mg (or equivalent) allowed
  • Modafinil
  • Hypericum perforatum (St. John's wort)

• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including the following:

  • Antibiotics (e.g., clarithromycin, erythromycin, or troleandomycin)
  • Antifungals (e.g., itraconazole, ketoconazole, fluconazole [> 150 mg daily], or voriconazole)
  • Antiretrovirals and protease inhibitors (e.g., delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, or lopinavir)
  • Calcium channel blockers (e.g., verapamil or diltiazem)
  • Antidepressants (e.g., nefazodone or fluvoxamine)
  • Gastrointestinal agents (e.g., cimetidine or aprepitant)
  • Grapefruit and grapefruit juice
• At least 6 months since prior and no concurrent amiodarone
• No herbal or alternative medicines or supplements ≥ 14 days before, during, and for 30 days after completion of study treatment

• No concurrent hormonal agents (e.g., birth control pills, ovarian hormonal replacement therapy, or raloxifene)

  • Adjuvant hormonal agents (e.g., tamoxifen, aromatase inhibitors) allowed after completion of chemotherapy as part of treatment for breast cancer
• No concurrent antiretroviral therapy for HIV-positive patients
• No concurrent digitalis or beta-blockers for congestive heart failure
• No concurrent arrhythmia or angina pectoris medication
• No other concurrent investigational agents or anticancer therapies, including cytotoxic agents or immunotherapy