Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Erlotinib in Treating Patients With Unresectable Liver Cancer and Liver Dysfunction

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	MDA-ID-01510 NCI-5349, NCT00047346, 5349

Objectives

Primary

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

Secondary

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

Entry Criteria

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)

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 16 weeks

Hematopoietic

• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 60,000/mm³
• 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

Expected Enrollment

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

Outcomes

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

Antitumor effect as measured by NCI RECIST criteria every 8 weeks

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

James Abbruzzese, MD, Protocol chair		Ph: 713-792-2828; 800-392-1611

Registry Information
Official Title		A Dose-Finding, Safety, And Pharmacokinetic Study Of The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor OSI-774 (NSC 718781) In Patients With Unresectable Hepatocellular Carcinoma And Moderate Hepatic Dysfunction
Trial Start Date		2002-08-14
Registered in ClinicalTrials.gov		NCT00047346
Date Submitted to PDQ		2002-08-30
Information Last Verified		2006-01-17
NCI Grant/Contract Number		N01-CA62461, P30-CA16672

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