• Response rate as measured by NCI RECIST criteria every 8 weeks [ Designated as safety issue: No ]
• Rate and duration of stable disease as measured by NCI RECIST criteria every 8 weeks [ Designated as safety issue: No ]
• Time to progression as measured by NCI RECIST criteria every 8 weeks [ Designated as safety issue: No ]
• Overall survival from registration till death [ Designated as safety issue: No ]
• Safety as measured by NCI RECIST criteria v3.0 continously [ Designated as safety issue: Yes ]
• Pharmacokinetic and pharmacodynamic profile by a compartmental and noncompartmental model during 1st course [ Designated as safety issue: No ]
• Correlated response with patient characteristics at end of study [ Designated as safety issue: No ]

• Response rate as measured by NCI RECIST criteria every 8 weeks
• Rate and duration of stable disease as measured by NCI RECIST criteria every 8 weeks
• Time to progression as measured by NCI RECIST criteria every 8 weeks
• Overall survival from registration till death
• Safety as measured by NCI RECIST criteria v3.0 continously
• Pharmacokinetic and pharmacodynamic profile by a compartmental and noncompartmental model during 1st course
• Correlated response with patient characteristics at end of study

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of erlotinib in treating patients who have liver cancer that cannot be surgically removed.

OBJECTIVES:

• Determine the 16-week progression-free survival of patients with unresectable hepatocellular carcinoma treated with erlotinib.
• Determine the objective response rate, rate and duration of stable disease, and time to progression in patients treated with this drug.
• Determine the median and overall survival of patients treated with this drug.
• Determine the pharmacokinetic and pharmacodynamic profiles of this drug in these patients.
• Determine the safety and tolerability of this drug in these patients.
• Correlate response to this drug with patient characteristics (e.g., age, disease stage, viral hepatitis status, pathologic grade of cirrhosis, Childs-Pugh status, performance status, serum values of alpha-fetoprotein, bilirubin, transaminases, and albumin, epidermal growth factor receptor expression, and development of skin rash during therapy).

OUTLINE: Patients are stratified according to epidermal growth factor receptor expression (low, 0-1+ vs high, 2-3+).

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

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients (40 per stratum) will be accrued for this study within 25-50 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatocellular carcinoma (HCC) not amenable to curative resection

  • No fibrolamellar HCC

• No prior therapy for HCC, including systemic chemotherapy, hepatic arterial infusion of chemotherapeutic agents or irradiated microspheres, and epidermal growth factor receptor-targeting agents

  • The following prior therapies are allowed provided previously treated lesions remain separate from those to be evaluated in present study

    • Surgery
    • Liver-directed therapy (e.g., radiofrequency ablation, transarterial embolization/chemoembolization, or percutaneous ethanol injection)

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques
• Must have paraffin tissue block or unstained slides from biopsy or surgical specimen
• No known brain metastases
• No ascites that are refractory to conservative management (e.g., sodium restriction to 50 mEq/day dietary sodium and fluid restrictions and/or diuretics)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 16 weeks

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 60,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin no greater than 1.8 mg/dL
• Albumin at least 2.5 g/dL
• AST/ALT no greater than 5 times upper limit of normal
• PT no greater than 1-3 seconds over normal
• No decompensated liver disease
• No jaundice
• No portosystemic encephalopathy (evidenced by confusion, asterixis, significant sleep disturbance, or hypothermia less than 36º Celsius)
• No hyponatremia with sodium less than 125 mEq/L
• No portal hypertension with bleeding esophageal or gastric varices within the past 3 months

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No gastrointestinal tract disease resulting in an inability to take oral medication or requirement for IV alimentation
• No active peptic ulcer disease

Ophthalmic

• No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
• No congenital abnormality (e.g., Fuch's dystrophy)

Other

• No other uncontrolled concurrent illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• No prior surgical therapy affecting absorption

Other

• More than 30 days since prior investigational agents
• No concurrent commercial or other investigational anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients