• Dose-limiting toxicity and maximum tolerated dose as measured by NCI CTCAE v3.0 continuously [ Designated as safety issue: Yes ]
• Pharmacokinetic and pharmacodynamic profile as measured by compartmental and noncompartmental models during first course of treatment [ Designated as safety issue: No ]

• Dose-limiting toxicity and maximum tolerated dose as measured by NCI CTCAE v3.0 continuously
• Pharmacokinetic and pharmacodynamic profile as measured by compartmental and noncompartmental models during first course of treatment

RATIONALE: Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor.

PURPOSE: Phase I trial to study the effectiveness of erlotinib in treating patients who have unresectable liver cancer and liver dysfunction.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of erlotinib in patients with unresectable hepatocellular carcinoma and moderate hepatic dysfunction.
• Determine the dose-limiting toxicity of this drug in these patients.
• Determine the pharmacokinetic and pharmacodynamic profiles of this drug in these patients.

Secondary

• Determine any possible antitumor effects of this drug, in terms of partial and complete response, in these patients.

OUTLINE: This is a dose-escalation study.

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

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 12-24 patients will be accrued for this study within 4-24 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable hepatocellular carcinoma (HCC) with or without extrahepatic metastasis

  • No fibrolamellar HCC
• No more than 2 prior therapies for HCC, including systemic chemotherapy, chemoembolization, hepatic arterial infusion of chemotherapeutic agents, and other novel agents

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• Moderate hepatic dysfunction with any of the following:

  • Bilirubin 2-4 g/dL
  • Albumin < 2.5 g/dL
  • Ascites
  • PT 2-4 seconds > upper limit of normal (ULN)
  • AST/ALT 2.6-10 times > ULN
• 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 ≥ 1,500/mm^3
• Platelet count ≥ 60,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• See Disease Characteristics
• No decompensated liver disease
• No jaundice
• No portosystemic encephalopathy (evidenced by confusion, asterixis, significant sleep disturbance, or hypothermia less than 36º Celsius)
• No hyponatremia < 130 mEq/L
• No portal hypertension with bleeding esophageal or gastric varices within the past 3 months

Renal

• Creatinine ≤ 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 significant traumatic injury within the past 21 days
• 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
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• No prior surgical therapy affecting absorption
• At least 21 days since prior major surgery

Other

• At least 4 weeks since any other prior agents and recovered
• No prior epidermal growth factor-receptor targeting therapies
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients