RATIONALE: Celecoxib may stop the growth of tumor cells by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining celecoxib with epirubicin may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining celecoxib with epirubicin in treating patients who have hepatocellular carcinoma (liver cancer).

Condition	Treatment or Intervention	Phase
advanced adult primary liver cancer localized unresectable adult primary liver cancer adult primary hepatocellular carcinoma	Drug: celecoxib  Drug: epirubicin  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

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

OUTLINE: This is a dose-escalation study of epirubicin.

• 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.

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

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

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/mm^3
• Platelet count at least 75,000/mm^3

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

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

Illinois
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting

Study chairs or principal investigators

Mary Mulcahy, MD,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000285669; NU-02I6; NCT00057980
Record last reviewed:  November 2004
Last Updated:  December 9, 2004
Record first received:  April 7, 2003
ClinicalTrials.gov Identifier:  NCT00057980
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08