Erlotinib in Treating Patients With Liver Cancer That Cannot be Surgically Removed

A Phase 2 Open-Label Study Of OSI-774 (NSC 718781) In Unresectable Hepatocellular Carcinoma

Phase II trial to study the effectiveness of erlotinib in treating patients who have liver cancer that cannot be surgically removed. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth

PRIMARY OBJECTIVES:

I. To assess progression-free survival (PFS) measured at 16 weeks following initiation of once daily continuous oral therapy with OSI-774 in patients with unresectable hepatocellular carcinoma.

SECONDARY OBJECTIVES:

I. To assess objective response rate, rate and duration of stable disease, time to progression, median and overall survival in this patient population, and any changes in tumor perfusion based on functional CT imaging.

II. To correlate response with patient characteristics including: age, disease stage (TNM, Okuda [6]), viral hepatitis status, pathologic grade of cirrhosis, Childs-Pugh status, Performance Status, serum values of: alpha feto-protein, bilirubin, transaminases, albumin; EGFR expression score by IHC; and development of skin rash during therapy.

III. To determine the pharmacokinetic and pharmacodynamic profile of OSI-774 in this patient population.

IV. To determine the safety and tolerability of OSI-774 in this patient population.

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.

Inclusion Criteria:

• 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)

• Performance status - ECOG 0-2

• At least 16 weeks

• Granulocyte count at least 1,500/mm^3

• Platelet count at least 60,000/mm^3

• Hemoglobin at least 10 g/dL

• 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

• Creatinine no greater than 2 mg/dL

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

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

• No active peptic ulcer disease

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

• No congenital abnormality (e.g., Fuch's dystrophy)

• 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

• No prior surgical therapy affecting absorption

• 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