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

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	MDA-ID-02008 NCI-5953, NCT00047333, 5953

Objectives

1. Determine the 16-week progression-free survival of patients with unresectable hepatocellular carcinoma treated with erlotinib.
2. Determine the objective response rate, rate and duration of stable disease, and time to progression in patients treated with this drug.
3. Determine the median and overall survival of patients treated with this drug.
4. Determine the pharmacokinetic and pharmacodynamic profiles of this drug in these patients.
5. Determine the safety and tolerability of this drug in these patients.
6. 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).

Entry Criteria

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)

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 16 weeks

Hematopoietic

• Granulocyte count at least 1,500/mm³
• Platelet count at least 60,000/mm³
• 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

Expected Enrollment

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

Outcomes

Progression-free survival as measured by NCI RECIST criteria at 16 weeks

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

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Melanie Thomas, MD, Protocol chair(Contact information may not be current)		Ph: 713-792-2828; 800-392-1611

Registry Information
Official Title		A Phase II Open-Label Study Of OSI-774 (NSC 718781) In Unresectable Hepatocellular Carcinoma
Trial Start Date		2002-08-14
Registered in ClinicalTrials.gov		NCT00047333
Date Submitted to PDQ		2002-08-30
Information Last Verified		2006-01-18
NCI Grant/Contract Number		N01-CM17003, P30-CA16672

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