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A Phase II Study of ZD1839 (Iressa, Gefitinib, NSC 715055) in Advanced Unresectable Hepatocellular Carcinoma

Phase 2
18 Years
Not Enrolling
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

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Trial Information

A Phase II Study of ZD1839 (Iressa, Gefitinib, NSC 715055) in Advanced Unresectable Hepatocellular Carcinoma


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,

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

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate in patients treated with ZD 1839

Outcome Description:

A 4.5-month (PFS) rate of 63% or more will be taken as evidence of activity in this patient population.

Outcome Time Frame:

From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, assessed up to 4.5 months

Safety Issue:


Principal Investigator

Bruce Giantonio

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

February 2004

Completion Date:

Related Keywords:

  • Adult Primary Hepatocellular Carcinoma
  • Advanced Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Eastern Cooperative Oncology Group Boston, Massachusetts  02215