Gefitinib in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer)
Gefitinib in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer)
Phase II trial to study the effectiveness of gefitinib in treating patients who have advanced
 unresectable hepatocellular carcinoma (liver cancer). Gefitinib may stop the growth of tumor
 cells by blocking the enzymes necessary for their growth
PRIMARY OBJECTIVES:

 I. Evaluate the ability of ZD1839 to improve progression free survival in patients with
 advanced unresectable hepatocellular carcinoma.

 II. Evaluate response rate of ZD1839 in advanced unresectable hepatocellular carcinoma.

 III. Evaluate the effect of ZD1839 on measurable disease in patients with unresectable
 hepatocellular carcinoma.

 IV. Evaluate the effect of ZD1839 on serum alpha-fetoprotein levels in patients with abnormal
 pretreatment serum levels.

 V. Evaluate toxicity of ZD1839 in advanced unresectable hepatocellular carcinoma.

 VI. Investigate biologic markers for outcome in patients with unresectable hepatocellular
 carcinoma treated with ZD1839.

 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.
Inclusion Criteria:

 -  Patients must have advanced unresectable hepatocellular carcinoma based on the
 following criteria:

 -  Histologically or cytologically confirmed, OR

 -  Alpha-fetoprotein > 400 ng if patient is not hepatitis surface antigen positive,
 OR

 -  Alpha-fetoprotein > 4000 ng if patient is hepatitis surface antigen positive

 -  NOTE: If available, tissue should be submitted to assess EGFR/pathway
 expression

 -  Patients must have measurable disease, defined as at least one lesion that can be
 accurately measured in at least one dimension (longest diameter to be recorded) as >=
 20 mm with conventional techniques or as >= 10 mm with spiral CT scan, assessed within
 4 weeks prior to randomization/registration

 -  Prior use of liver-directed therapy (radio-frequency ablation, cryoablation,
 percutaneous ethanol injection, chemo-embolization, hepatic artery embolization and
 hepatic artery infused FUDR) is allowed, provided the patient has either progressive
 hepatic disease or measurable extrahepatic disease

 -  ECOG performance status of 0, 1 or 2

 -  Leukocytes >= 2,000/uL OR

 -  Absolute neutrophil count >= 1,000/uL

 -  Platelets >= 50,000/uL

 -  Patients may not have Child Pugh Scale's class C cirrhosis

 -  AST (SGOT) =< 5 x institutional upper limit of normal

 -  Total bilirubin =< 2 x institutional upper limit of normal

 -  Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min for
 patients with creatinine levels above institutional normal

 -  PT =< 6 seconds over control

 -  INR =< 2.3

 -  Albumin >= 2.8 g/dL

 -  Pregnant women are excluded from this study; sexually active women of child bearing
 potential and men must agree to use adequate contraception (hormonal or barrier method
 of birth control) for the duration of their participation in the study; should a woman
 become pregnant or suspect she is pregnant while participating in this study, she
 should inform her treating physician immediately

 -  Women who are breastfeeding a child are not eligible, unless they discontinue the
 breastfeeding

 -  Patients must not have had prior systemic chemotherapy, biologic therapy or
 antiangiogenesis therapy; prior therapy with interferon alpha or interferon beta for
 treatment of hepatitis B or C is allowed provided

 -  Prior palliative radiotherapy is permissible provided it has been completed 2 weeks
 from registration and the patient has measurable disease outside the radiation field

 -  Patients may not be receiving any other investigational agents

 -  Patients must not have a history of other malignancies that are active and require
 therapy (other than local therapies for non melanoma skin cancers)

 -  Patients must not have known brain metastases; their poor prognosis would present
 challenges and their tendency to develop progressive neurologic dysfunction would
 confound the evaluation of neurologic and other adverse events

 -  Patients must not have a history of allergic reactions attributed to compounds of
 similar chemical or biologic composition to ZD1839

 -  Patients must not have had prior treatment with an EGFR inhibitor

 -  Patients must not have a history of an uncontrolled intercurrent illness including,
 but not limited to, ongoing or active infection, symptomatic congestive heart failure,
 unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
 that would limit compliance with study requirements

 -  Patients must not be HIV-positive and receiving combination anti-retroviral therapy;
 this therapy might have possible pharmacokinetic interactions with ZD1839; appropriate
 studies will be undertaken in patients receiving combination anti-retroviral therapy
 when indicated

 -  Patients must not use the following known inducers of CYP3A4: carbamazepine,
 dexamethasone, ethosuxamide, glucocorticoids, griseofulvin, nafcillin, nelfinavir
 nevirapine, oxcarbazepine, phenobarbital, phenylbutazone, phenytoin, primidone,
 progesterone, rifabutin, rifampin, rofecoxib, St John's Wort, sulfadimidine,
 sulfinpyrazone, troglitazone, efavirenz, modafinil, and rifapentine; drugs that induce
 CYP3A4 enzymes can cause reductions in ZD1839 plasma concentrations below levels
 thought to be biologically active

 -  Patients must not be candidates for surgical resection or liver transplantation

 -  Patients must not have grade 3 or grade 4 encephalopathy