RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have advanced unresectablehepatocellular carcinoma (liver cancer ).

Condition	Treatment or Intervention	Phase
advanced adult primary liver cancer recurrent adult primary liver cancer adult primary hepatocellular carcinoma localized unresectable adult primary liver cancer	Drug: gefitinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the 4.5-month progression-free survival rate in patients with advanced unresectable hepatocellular carcinoma treated with gefitinib.

Secondary

• Determine the response rate (complete and partial), in terms of the effects of this drug on measurable disease and serum alpha-fetoprotein levels, in these patients.
• Determine the overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Correlate epidermal growth factor expression at baseline with clinical response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 years from study entry.

PROJECTED ACCRUAL: A total of 23-59 patients will be accrued for this study within 19 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of advanced unresectable hepatocellular carcinoma based on 1 of the following criteria:
• Histologically or cytologically confirmed disease
• Hepatitis B surface antigen negative and alpha-fetoprotein greater than 400 ng/mL
• Hepatitis B surface antigen positive and alpha-fetoprotein greater than 4,000 ng/mL
• At least 1 unidimensionally measurable lesion
• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Outside prior radiotherapy field
• No known brain metastases
• Ineligible for surgical resection or liver transplantation

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,000/mm^3
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic

• See Disease Characteristics
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 5 times ULN
• PT no greater than 6 seconds over control
• INR no greater than 2.3
• Albumin at least 2.8 g/dL
• No Child Pugh Scale class C cirrhosis

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

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

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other active malignancy requiring therapy except nonmelanoma skin cancer
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to gefitinib
• No psychiatric illness or social situation that would preclude study compliance
• No grade 3 or 4 encephalopathy
• No other concurrent uncontrolled illness
• No ongoing or active infection

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy
• Prior interferon alfa or interferon beta for hepatitis B or C allowed provided the therapy was completed before the diagnosis of hepatocellular carcinoma
• No prior antiangiogenesis therapy

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• No concurrent dexamethasone
• No concurrent glucocorticoids
• No concurrent progesterone

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior palliative radiotherapy

Surgery

• Not specified

Other

• Prior liver-directed therapy (i.e., radiofrequency ablation, cryoablation, percutaneous ethanol injection, chemo-embolization, hepatic artery embolization, and hepatic artery-infused floxuridine) allowed provided patient has progressive hepatic disease or measurable extrahepatic disease
• No prior epidermal growth factor inhibitor therapy
• No other concurrent investigational or commercial anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent inducers of CYP3A4, including the following:
• Carbamazepine
• Ethosuximide
• Griseofulvin
• Nafcillin
• Nelfinavir
• Nevirapine
• Oxcarbazepine
• Phenobarbital
• Phenylbutazone
• Phenytoin
• Primidone
• Rifabutin
• Rifampin
• Rofecoxib
• Hypericum perforatum (St. John's wort)
• Sulfadimidine
• Sulfinpyrazone
• Troglitazone
• Efavirenz
• Modafinil
• Rifapentine

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5216,  United States
      Veterans Affairs Medical Center - Palo Alto, Palo Alto,  California,  94304-1290,  United States
Colorado
      CCOP - Colorado Cancer Research Program, Incorporated, Denver,  Colorado,  80224,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
      Veterans Affairs Medical Center - Gainesville, Gainesville,  Florida,  32608-1197,  United States
      Veterans Affairs Medical Center - Miami, Miami,  Florida,  33125,  United States
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Georgia
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Iowa
      Burgess Health Center, Onawa,  Iowa,  51040,  United States
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Des Moines General Hospital, Des Moines,  Iowa,  50309,  United States
      Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States
      Mercy Cancer Center at Mercy Medical Center-Des Moines, Des Moines,  Iowa,  50314,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
      Tufts - New England Medical Center, Boston,  Massachusetts,  02111,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417-2399,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  United States
      Veterans Affairs Medical Center - Omaha, Omaha,  Nebraska,  68105,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08903,  United States
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07019,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
      MBCCOP-Our Lady of Mercy Cancer Center, Bronx,  New York,  10466,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States
      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States
Pennsylvania
      Abramson Cancer Center at University of Pennsylvania Medical Center, Philadelphia,  Pennsylvania,  19104,  United States
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States
      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15236,  United States
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States
      Veterans Affairs Medical Center - Pittsburgh, Pittsburgh,  Pennsylvania,  15240,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212-2637,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226-3596,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States
Australia, New South Wales
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru
Puerto Rico
      MBCCOP - San Juan, San Juan,  00921-3201,  Puerto Rico
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico
      Veterans Affairs Medical Center - San Juan, San Juan,  00927-5800,  Puerto Rico
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Bruce J. Giantonio, MD,  Study Chair,  University of Pennsylvania Health Systems   
Jordan D. Berlin, MD,  Vanderbilt-Ingram Cancer Center   
Peter J. O'Dwyer, MD, BCh,  University of Pennsylvania Cancer Center   

Study ID Numbers:  CDR0000335058; ECOG-E1203
Record last reviewed:  October 2004
Last Updated:  October 13, 2004
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00071994
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08