Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI ECOG-E1203 E1203, NCT00071994

Objectives

Primary

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

Secondary

1. 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.
2. Determine the overall survival of patients treated with this drug.
3. Determine the toxicity of this drug in these patients.
4. Correlate epidermal growth factor expression at baseline with clinical response in patients treated with this drug.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,000/mm³
• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 50,000/mm³

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

Expected Enrollment

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

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.

O'Dwyer PJ, Giantonio BJ, Levy DE, et al.: Gefitinib in advanced unresectable hepatocellular carcinoma: results from the Eastern Cooperative Oncology Group's study E1203. [Abstract] J Clin Oncol 24 (Suppl 18): A-4143, 213s, 2006.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Bruce Giantonio, MD, Protocol chair(Contact information may not be current)		Ph: 215-662-8624
Jordan Berlin, MD, Protocol co-chair		Ph: 615-322-4967; 800-811-8480 Email: jordan.berlin@vanderbilt.edu
Peter O'Dwyer, MD, BCh, Protocol co-chair		Ph: 215-662-7606 Email: peter.odwyer@uphs.upenn.edu

Registry Information
Official Title		A Phase II Study Of ZD1839 (Iressa, Gefitinib, NSC 715055) In Advanced Unresectable Hepatocellular Carcinoma
Trial Start Date		2004-02-06
Registered in ClinicalTrials.gov		NCT00071994
Date Submitted to PDQ		2003-09-11
Information Last Verified		2005-06-15
NCI Grant/Contract Number		CA21115

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