RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well lapatinib works in treating patients with unresectable liver or biliary tract cancer.

Condition	Treatment or Intervention	Phase
adult primary liver cancer extrahepatic bile duct cancer Gallbladder Cancer unresectable extrahepatic bile duct cancer unresectable gallbladder cancer	Drug: lapatinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the objective response rate (complete response and partial response) in patients with unresectable hepatocellular carcinoma or biliary tract carcinoma treated with lapatinib.

Secondary

• Determine 6-month disease-free survival in patients treated with this drug.
• Determine the toxicity profile of this drug in these patients.
• Determine median overall survival and 6- and 12-month survival rates in patients treated with this drug.
• Correlate target epidermal growth factor receptor gene and protein expression and the genes that regulate cell cycle and apoptosis with clinical outcome in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 50 patients (25 with hepatocellular carcinoma and 25 with biliary tract carcinoma) will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 75,000/mm^3

Hepatic

• 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)

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• Ejection fraction normal by echocardiogram or MUGA
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• 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)

Other

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy

Chemotherapy

• See Radiotherapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No prior cumulative doxorubicin dose > 450 mg/m^2

Endocrine therapy

• At least 14 days since prior and no concurrent glucocorticoids (e.g., dexamethasone or equivalent [dose > 1.5 mg/day])

Radiotherapy

• 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)

Surgery

• No prior surgical procedure affecting absorption
• More than 3 weeks since prior major surgery

Other

• 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

Study chairs or principal investigators

Tanios Bekaii-Saab, MD,  Study Chair,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000420830; OSU-0447; NCI-6696
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  April 5, 2005
ClinicalTrials.gov Identifier:  NCT00107536
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08