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 a