Celecoxib and Erlotinib in Treating Patients With Liver Cancer

September 13, 2012 updated by: University of California, San Francisco

A Phase I/II Study of Celecoxib and Erlotinib Hydrochloride as Adjuvant Therapy for High Risk Patients With a History of Hepatocellular Carcinoma

RATIONALE: Celecoxib and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Celecoxib may also stop the growth of liver cancer by blocking blood flow to the tumor.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving celecoxib together with erlotinib and to see how well they work in treating patients with liver cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the safety of adjuvant celecoxib and erlotinib hydrochloride for patients with hepatocellular carcinoma (HCC) at high risk for recurrence. (phase I)
  • Assess disease-free and overall survival of patients treated with adjuvant celecoxib and erlotinib hydrochloride. (phase II)

Secondary

  • Determine the maximum tolerated dose of celecoxib and erlotinib hydrochloride for the phase II portion of this trial. (phase I)

OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study. Patients are assigned to a treatment according to Child-Pugh class of cirrhosis (class A/noncirrhotic vs class B).

  • Phase I: Patients receive oral celecoxib once or twice daily and oral erlotinib hydrochloride once daily. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of celecoxib and erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Separate dose escalations are conducted in the 2 groups according to liver dysfunction.

  • Phase II: Patients receive celecoxib and erlotinib hydrochloride as in phase I at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Histological evidence of hepatocellular carcinoma (HCC)

    • No evidence of residual or recurrent disease

  • Received 1 of the following therapies:

    • Tumor resection between 4-8 weeks prior to study enrollment
    • Transarterial chemo-embolization between the past 4-8 weeks
    • Radiofrequency ablation and percutaneous ethanol injection (sequential or combinations thereof) between the past 2-8 weeks

  • Meets 1 of the following high-risk features for recurrence:

    • History of resection of a single HCC > 5 cm
    • History of multifocal HCC (includes microsatellite disease found at time of resection)
    • History of vascular invasion (macro or micro)
    • History of poorly differentiated HCC
    • Underlying cirrhosis
  • No Child-Pugh class C cirrhosis

PATIENT CHARACTERISTICS:

  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine ≤ 2.0 mg/dL
  • Bilirubin ≤ 2.0 mg/dL
  • AST/ALT ≤ 3 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • INR ≤ 1.5 times ULN
  • Albumin ≥ 2.5 g/dL
  • ECOG performance status 0-2
  • Life expectancy ≥ 2 years
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
  • No other malignancy within the past 5 years except nonmelanoma skin cancer
  • Patients must agree not to wear contact lenses
  • No history of ulcer disease or gastrointestinal bleeding
  • No myocardial infarction within the past 18 months
  • No cerebral vascular event within the past 18 months
  • No history of aspirin or NSAID-induced asthma
  • No history of Gilbert's syndrome
  • No history of hypersensitivity reaction or allergy to sulfa drugs, aspirin, or other NSAIDs
  • No liver transplantation candidates for phase I portion of the study
  • No New York Heart Association class III or IV cardiac disease
  • No interstitial lung disease
  • No gastrointestinal disease prohibiting oral medication or requiring IV alimentation
  • No active peptic ulcer disease
  • No unstable angina pectoris
  • No ongoing, active, or untreated infection
  • No hypersensitivity to celecoxib
  • No rising alpha-fetal protein (AFP) not attributable to hepatitis B or C virus
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

  • No prior liver transplantation
  • No prior chemotherapy or biologic therapy in the adjuvant setting
  • No prior chest or mantle radiotherapy
  • No concurrent aspirin or other nonsteroidal anti-inflammatory drug (NSAID)
  • No concurrent interferon
  • No concurrent oral steroids
  • No concurrent anticoagulant therapy
  • No concurrent CYP3A4 inducers or inhibitors
  • No concurrent commercial or other investigational anticancer agents or therapies
  • No concurrent selective cyclooxygenase-2 inhibitors
  • No concurrent antineoplastic or antitumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety (phase I)
Disease-free survival (phase II)

Secondary Outcome Measures

Outcome Measure
Overall survival (phase II)
Maximum tolerated dose (phase I)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Alan P. Venook, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Study Registration Dates

First Submitted

February 16, 2006

First Submitted That Met QC Criteria

February 16, 2006

First Posted (Estimate)

February 17, 2006

Study Record Updates

Last Update Posted (Estimate)

September 17, 2012

Last Update Submitted That Met QC Criteria

September 13, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000458055
  • UCSF-04459
  • UCSF-H43059-26066-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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