Epirubicin and Celecoxib in Treating Patients With Hepatocellular Carcinoma

Northwestern University

Status and phase

Completed

Phase 2

Phase 1

Conditions

Liver Cancer

Treatments

Drug: celecoxib

Drug: epirubicin hydrochloride

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00057980

NU 02I6

NU-02I6

Details and patient eligibility

About

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).

Full 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.

Enrollment

8 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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