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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (erlotinib hydrochloride)<br>Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: erlotinib hydrochloride<br>* Given PO<br>* Other names: OSI-774;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Summarized by Kaplan-Meier curves, from which medians and progression-free survival can be attained. | Time from initiation of therapy until documented disease progression, assessed at 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Summarized by estimates and standard errors. | Up to 4 years | 
| Rate of stable disease | Summarized by estimates and standard errors. | Up to 4 years | 
| Duration of stable disease | Summarized by Kaplan-Meier curves, from which medians and overall duration of stable disease can be attained. | From the start of the treatment until the criteria for progression are met, assessed up to 4 years | 
| Time to progression | Summarized by Kaplan-Meier curves, from which medians and time to progression can be attained. | Up to 4 years | 
| Overall survival | Summarized by Kaplan-Meier curves, from which medians and overall survival can be attained. | Up to 4 years |