Gefitinib in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00071994
First received: November 4, 2003
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Drug: gefitinib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of ZD1839 (Iressa, Gefitinib, NSC 715055) in Advanced Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival rate in patients treated with ZD 1839 [ 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 ] [ Designated as safety issue: No ]
    A 4.5-month (PFS) rate of 63% or more will be taken as evidence of activity in this patient population.


Secondary Outcome Measures:
  • Response (CR+PR) measured by RECIST [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Grade 3 or higher toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • EGFR expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: February 2004
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gefitinib)
Patients receive oral gefitinib daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071994

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Bruce Giantonio Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00071994     History of Changes
Other Study ID Numbers: NCI-2012-02948, E1203, U10CA021115, CDR0000335058
Study First Received: November 4, 2003
Last Updated: February 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014