Epirubicin and Celecoxib in Treating Patients With Hepatocellular Carcinoma - Full Text View

Sponsor:	Robert H. Lurie Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00057980

Purpose

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).

Condition	Intervention	Phase
Liver Cancer	Drug: celecoxib Drug: epirubicin hydrochloride	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I/II Study of Epirubicin and Celecoxib for Hepatocellular Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer

Drug Information available for: Epirubicin hydrochloride Epirubicin Celecoxib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of epirubicin [ Designated as safety issue: Yes ]
Response rate [ Designated as safety issue: No ]
Survival at 6 months [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity profile [ Designated as safety issue: Yes ]
Serum vascular endothelial growth factor levels in correlation to response [ Designated as safety issue: No ]
Cyclooxygenase-2 expression in tumor tissue and nonmalignant liver tissue in correlation to response [ Designated as safety issue: No ]

Study Start Date:	October 2002
Estimated Primary Completion Date:	December 2006 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00057980

Locations

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

Sponsors and Collaborators

Robert H. Lurie Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Mary Mulcahy, MD

Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000285669, NU-02I6
Study First Received:	April 7, 2003
Last Updated:	January 24, 2009
ClinicalTrials.gov Identifier:	NCT00057980 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

advanced adult primary liver cancer
localized unresectable adult primary liver cancer
adult primary hepatocellular carcinoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Carcinoma, Hepatocellular
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Liver Neoplasms
Neoplasms by Site
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Celecoxib
Digestive System Neoplasms

Neoplasms by Histologic Type
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Epirubicin
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Analgesics, Non-Narcotic
Peripheral Nervous System Agents
Antirheumatic Agents
Adenocarcinoma
Central Nervous System Agents
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009