Clinical trial NCT00436566 (phase 2, status: completed)
Conditions: breast cancer, cardiac toxicity
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: cyclophosphamide, doxorubicin hydrochloride, lapatinib ditosylate, paclitaxel
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O, CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
Eligibility criteria:

        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