Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer

Inclusion Criteria

• •Histologically confirmed diagnosis of 1 of the following:
• •* Hepatocellular carcinoma (hepatoma)
• •* Child-Pugh classification score ≤ 7
• •* Biliary tract carcinoma
• •Surgically unresectable disease
• •Measurable disease
• •* At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• •Fresh tissue or paraffin embedded tissue from tumor blocks available
• •No ampulla of Vater tumors
• •No known brain metastases
• •Performance status - ECOG 0-1
• •Performance status - Karnofsky 60-100%
• •More than 12 weeks
• •Absolute neutrophil count ≥ 1,500/mm\^3
• •Platelet count ≥ 75,000/mm\^3
• •Bilirubin ≤ 2 times upper limit of normal (ULN)
• •AST and ALT ≤ 3 times ULN
• •Albumin ≥ 2.5 mg/dL
• •INR ≤ 1.5 (for patients not receiving an anticoagulant)
• •Live metastases or stable chronic liver disease allowed
• •No current active hepatic or biliary disease except for Gilbert's syndrome or asymptomatic gallstone
• •Creatinine ≤ 2 mg/dL
• •Ejection fraction normal by echocardiogram or MUGA
• •No unstable angina pectoris
• •No cardiac arrhythmia
• •Able to swallow and retain oral medication
• •No gastrointestinal (GI) tract disease resulting in an inability 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)
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •No significant traumatic injury within the past 3 weeks
• •No active or ongoing infection
• •No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib
• •No psychiatric illness or social situation that would preclude study compliance
• •No other uncontrolled illness
• •No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• •More than 4 weeks since prior biologic therapy
• •More than 4 weeks since prior immunotherapy
• •See Radiotherapy
• •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• •No prior cumulative doxorubicin dose \> 450 mg/m\^2
• •At least 14 days since prior and no concurrent glucocorticoids (e.g., dexamethasone or equivalent \[dose \> 1.5 mg/day\])
• •More than 4 weeks since prior radiotherapy
• •More than 12 weeks since prior radiotherapy with or without a fluoropyrimidine as a radiosensitizer (for patients with biliary carcinoma only)
• •No prior surgical procedure affecting absorption
• •More than 3 weeks since prior major surgery
• •Recovered from all prior therapy
• •No more than 1 prior systemic anticancer therapy, including chemoembolization
• •No prior epidermal growth factor receptor-targeting therapy
• •More than 6 weeks since prior cryotherapy, radiofrequency ablation, ethanol injection, transarterial chemoembolization, or photodynamic therapy AND meets both of the following criteria:
• •* Indicator lesion is outside the area of prior treatment OR there is clear evidence of disease progression associated with the sole indicator lesion
• •* Edges of indicator lesion are clearly distinct by CT scan
• •At least 7 days since prior and no concurrent H2 inhibitors or proton pump inhibitors
• •* Concurrent antacids allowed provided they are administered \> 1 hour before and \> 1 hour after study drug administration
• •At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
• •* Clarithromycin
• •* Erythromycin
• •* Troleandomycin
• •* Delaviridine
• •* Ritonavir
• •* Indinavir
• •* Saquinavir
• •* Nelfinavir
• •* Amprenavir
• •* Lopinavir
• •* Itraconazole
• •* Ketoconazole
• •* Voriconazole
• •* Fluconazole (doses ≤ 150 mg/day are allowed)
• •* Nefazodone
• •* Fluvoxamine
• •* Verapamil
• •* Diltiazem
• •* Cimetidine
• •* Aprepitant
• •* Grapefruit and grapefruit juice
• •* Bitter orange
• •At least 6 months since prior and no concurrent amiodarone
• •At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:
• •* Phenytoin
• •* Carbamazepine
• •* Phenobarbital
• •* Oxcarbazepine
• •* Efavirenz
• •* Nevirapine
• •* Rifampin
• •* Rifabutin
• •* Rifapentine
• •* Roxithromycin
• •* Telithromycin
• •* Hypericum perforatum (St. John's wort)
• •* Modafinil
• •No concurrent combination antiretroviral therapy for HIV-positive patients
• •No other concurrent investigational agents
• •No other concurrent anticancer therapy
• •Concurrent oral anticoagulants (e.g., coumadin or warfarin) allowed provided there is increased vigilance in monitoring INR