Epirubicin and Celecoxib in Treating Patients With Hepatocellular Carcinoma

Study Overview
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Brief Summary
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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: This phase I/II trial is studying the side effects and best dose of epirubicin when given together with celecoxib and to see how well it works in treating patients with hepatocellular carcinoma (liver cancer).

Detailed Description
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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. 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. 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.

Official Title
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Phase I/II Study of Epirubicin and Celecoxib for Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: epirubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: epirubicin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of epirubicin |  |  | 
| Response rate |  |  | 
| Survival at 6 months |  |  | 
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced adult primary liver cancer, localized unresectable adult primary liver cancer, adult primary hepatocellular carcinoma