Liver Cancer
Conditions
Keywords
advanced adult primary liver cancer, localized unresectable adult primary liver cancer, adult primary hepatocellular carcinoma
Brief summary
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
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.
Interventions
DRUGcelecoxib
DRUGepirubicin hydrochloride
Sponsors
National Cancer Institute (NCI)
Northwestern University
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of epirubicin | — |
| Response rate | — |
| Survival at 6 months | — |
| Overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Serum vascular endothelial growth factor levels in correlation to response | — |
| Cyclooxygenase-2 expression in tumor tissue and nonmalignant liver tissue in correlation to response | — |
| Toxicity profile | — |
Countries
United States
Outcome results
None listed