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

Alternate Title

Epirubicin and Celecoxib in Treating Patients With Hepatocellular Carcinoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	NCI	NU-02I6 NCT00057980

Objectives

1. Determine the maximum tolerated dose of epirubicin when administered with celecoxib in patients with hepatocellular carcinoma.
2. Determine the response rate in patients treated with this regimen.
3. Determine the 6-month and overall survival of patients treated with this regimen.
4. Determine the toxicity profile of this regimen in these patients.
5. Determine the effects of this regimen on serum levels of vascular endothelial growth factor and correlate these effects with response in these patients.
6. Correlate the expression of cyclooxygenase-2 in tumor tissue and nonmalignant liver tissue with response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Diagnosis of localized or metastatic hepatocellular carcinoma (HCC) by 1 of the following:
  • Biopsy
  • Alpha-fetoprotein (AFP) measurement (greater than 400 ng/mL if hepatitis B surface antigen [HBsAg] is negative OR greater than 1,000 ng/mL if HBsAg is positive)



• Not amenable to surgical resection or liver-directed therapy



• Measurable or evaluable disease*

   [Note: *Changes in AFP alone are not sufficient]




• Child-Pugh score A or B

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for HCC

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 75,000/mm³

Hepatic

• Bilirubin no greater than 3.0 mg/dL
• AST no greater than 5 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• LVEF greater than 45% by MUGA or echocardiogram

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No requirement for nonsteroidal anti-inflammatory drugs (NSAIDs) except low-dose (81 mg) aspirin
• No known hypersensitivity to aspirin or other NSAIDs
• No contraindication to cyclooxygenase-2 (COX-2) inhibitor therapy

Expected Enrollment

A total of 3-52 patients (3-15 for phase I and 12-37 for phase II) will be accrued for this study.

Outcomes

Maximum tolerated dose of epirubicin
Response rate
Survival at 6 months
Overall survival

Toxicity profile
Serum vascular endothelial growth factor levels in correlation to response
Cyclooxygenase-2 expression in tumor tissue and nonmalignant liver tissue in correlation to response

Outline

This is a dose-escalation study of epirubicin.

• Phase I:Patients receive epirubicin IV over 20 minutes on day 1 and oral celecoxib twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-5 patients receive escalating doses of epirubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 3 of 5 patients experience dose-limiting toxicity.




• Phase II: Additional patients are accrued and treated as in phase I at the MTD of epirubicin.

Patients are followed every 3 months.

Trial Contact Information

Trial Lead Organizations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Mary Mulcahy, MD, Protocol chair		Ph: 312-695-6180

Registry Information
Official Title		Phase I/II Study of Epirubicin and Celecoxib for Hepatocellular Carcinoma
Trial Start Date		2002-10-31
Trial Completion Date		2006-12-21 (estimated)
Registered in ClinicalTrials.gov		NCT00057980
Date Submitted to PDQ		2003-02-10
Information Last Verified		2006-01-05
NCI Grant/Contract Number		CA60553

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