Clinical trial NCT00331630 (early phase 1, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: lapatinib ditosylate, paclitaxel albumin-stabilized nanoparticle formulation
SMILES: 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@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C
Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed breast cancer

               -  Clinical stage I-III disease

          -  Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
             conventional techniques OR ≥ 10 mm with spiral CT scan

          -  HER2/neu 3+ by immunohistochemistry or positive by fluorescent in situ hybridization

          -  No known brain metastases

          -  Hormone receptor status unspecified

        PATIENT CHARACTERISTICS:

          -  Menopausal status not specified

          -  Male or female

          -  Life expectancy > 12 weeks

          -  ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%

          -  WBC ≥ 3,000/mm^3

          -  Absolute neutrophil count ≥ 1,500 mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Total bilirubin normal

          -  AST and ALT ≤ 2.5 times upper limit of normal

          -  Creatinine normal OR creatinine clearance ≥ 60 mL/min

          -  LVEF ≥ 50% as measured by echocardiogram or MUGA scan

          -  No other malignancy within the past year

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Able to swallow and retain oral medication

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to lapatinib

          -  No ongoing or active infection

          -  No symptomatic congestive heart failure

          -  No unstable angina pectoris

          -  No cardiac arrhythmia

          -  No psychiatric illness or social situation that would preclude study compliance

          -  No other uncontrolled illness

          -  No gastrointestinal (GI) tract disease that would preclude ability to take oral
             medication

          -  No malabsorption syndrome

          -  No requirement for IV alimentation

          -  No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

        PRIOR CONCURRENT THERAPY:

          -  No prior chemotherapy, immunotherapy, radiotherapy, or hormonal therapy for breast
             cancer

          -  No prior treatment with epidermal growth factor receptor targeting therapies

          -  No prior surgical procedures affecting absorption

          -  No prior surgery for breast cancer

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

               -  Dexamethasone or dexamethasone equivalent dose ≥ 1.5 mg/day, including any of the
                  following:

                    -  Cortisone (≥ 50 mg/day)

                    -  Hydrocortisone (≥ 40 mg/day)

                    -  Prednisone (≥ 10 mg/day)

                    -  Methylprednisolone (≥ 8 mg/day)

               -  Phenytoin

               -  Carbamazepine

               -  Phenobarbital

               -  Efavirenz

               -  Nevirapine

               -  Rifampin

               -  Rifabutin

               -  Rifapentine

               -  Hypericum perforatum (St. John's wort)

               -  Modafinil

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

               -  Clarithromycin

               -  Erythromycin

               -  Troleandomycin

               -  Delavirdine

               -  Ritonavir

               -  Indinavir

               -  Saquinavir

               -  Nelfinavir

               -  Amprenavir

               -  Lopinavir

               -  Itraconazole

               -  Ketoconazole

               -  Voriconazole

               -  Fluconazole (doses up to 150 mg/day are permitted)

               -  Nefazodone

               -  Fluvoxamine

               -  Verapamil

               -  Diltiazem

               -  Cimetidine

               -  Aprepitant

               -  Grapefruit or its juice

          -  At least 6 months since prior and no concurrent amiodarone

          -  At least 2 days since prior and no concurrent gastric pH modifiers*, including any of
             the following:

               -  Cimetidine

               -  Ranitidine

               -  Nizatidine

               -  Famotidine

               -  Omeprazole

               -  Esomeprazole

               -  Rabeprazole

               -  Pantoprazole

               -  Lansoprazole

          -  NOTE: *Antacids are allowed within 1 hour before and after administration of study
             drug

          -  No other concurrent investigational agents

          -  No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
             immunotherapy, or antitumor hormonal therapy

          -  No concurrent herbal (alternative) medicines

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  Concurrent bisphosphonates allowed