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

PURPOSE: Phase II trial to study the effectiveness of erlotinib in treating patients who have unresectableliver, bile duct, or gallbladder cancer.

Condition	Treatment or Intervention	Phase
adult primary liver cancer extrahepatic bile duct cancer Gallbladder Cancer	Drug: erlotinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the progression-free rate at 24 weeks in patients with unresectable hepatocellular or biliary carcinoma treated with erlotinib.
• Determine the toxicity profile of this drug in these patients.
• Determine the objective response rate of patients treated with this drug.
• Determine the overall and progression-free survival of patients treated with this drug.
• Correlate epidermal growth factor receptor protein levels with clinical outcome in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups according to cancer type (hepatocellular vs biliary).

Patients receive oral erlotinib once daily. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for up to 3 years.

PROJECTED ACCRUAL: A total of 78 patients (39 per group) will be accrued for this study within 13 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatocellular or biliary carcinoma
• Unresectable
• Noninvasive diagnosis of unresectable hepatocellular carcinoma byhypervascular mass on CT scan and alpha fetoprotein greater than 100 ng/mL allowed
• Measurable disease
• At least 1 lesion with diameter at least 2.0 cm
• Child-Pugh classification of A or B
• Indicator lesions must be outside of prior treatment area and edges of lesions must be clearly distinct
• Patients whose sole indicator lesion is inside prior treatment area are eligible provided the lesion shows clear evidence of disease progression
• No Ampulla of Vater tumors
• No known CNS metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN
• INR no greater than 1.5 (for patients not receiving anticoagulation)

Renal:

• Creatinine no greater than 2 mg/dL
• Albumin at least 2.5 g/dL

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal:

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

Ophthalmic:

• No known abnormalities of the cornea including, but not limited to:
• Dry eye syndrome or Sjögren's syndrome
• Congenital abnormality (e.g., Fuch's dystrophy)
• Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• Abnormal corneal sensitivity test (Schirmer test or similar tear production test)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant traumatic injury within the past 3 weeks
• No other malignancy in the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma of the cervix
• No ongoing or active infection
• No uncontrolled concurrent medical or psychiatric illness or social situation that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• More than 4 weeks since prior immunotherapy or biologic therapy
• No concurrent immunotherapy

Chemotherapy:

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No more than 1 prior systemic anticancer therapy
• Chemoembolization considered 1 prior chemotherapeutic regimen
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent anti-cancer hormonal agents

Radiotherapy:

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy (including whole brain irradiation for documented CNS metastasis)

Surgery:

• More than 3 weeks since prior major surgery
• More than 6 weeks since prior cryotherapy
• No prior procedures affecting absorption

Other:

• Recovered from prior therapy
• More than 6 weeks since prior radiofrequency ablation, ethanol injection, or photodynamic therapy
• No prior epidermal growth factor receptor-targeting therapy
• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No other concurrent investigational therapy or supportive care
• No other concurrent anticancer medications

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States
District of Columbia
      Howard University Hospital, Washington,  District of Columbia,  20060-0001,  United States
Florida
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Missouri
      Washington University School of Medicine, Saint Louis,  Missouri,  63110,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Study chairs or principal investigators

Philip A. Philip, MD, PhD, FRCP,  Study Chair,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000069285; MAYO-MC0152; NCI-5429
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033462
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08