Epirubicin and Celecoxib in Treating Patients With Hepatocellular Carcinoma

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

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).

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Drug: celecoxib; Drug: epirubicin hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate
Overall survival
Survival at 6 months
Maximum tolerated dose of epirubicin

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Mary Mulcahy, MD, Robert H. Lurie Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: April 7, 2003
• First Submitted That Met QC Criteria: April 8, 2003
• First Posted (Estimate): April 9, 2003

Study Record Updates

• Last Update Posted (Estimate): June 11, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: advanced adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclooxygenase 2 Inhibitors; Epirubicin; Celecoxib
• Other Study ID Numbers: NU 02I6; NU-02I6