Intervention: Lapatinib
Trial phase: Phase 2
ATC code: L01EH01 | L01XE07
SMILES: CS(=O)(=O)CCNCc1ccc(-c2ccc3ncnc(Nc4ccc(OCc5cccc(F)c5)c(Cl)c4)c3c2)o1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 26
Group description: Patients receive oral lapatinib ditosylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

lapatinib ditosylate

laboratory biomarker analysis: Correlative studies
Eligibility criteria:
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