Celecoxib and Erlotinib in Treating Patients With Liver Cancer

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by:
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00293436
First received: February 16, 2006
Last updated: September 13, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Drug: celecoxib
Drug: erlotinib hydrochloride
Procedure: adjuvant therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Celecoxib and Erlotinib Hydrochloride as Adjuvant Therapy for High Risk Patients With a History of Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Safety (phase I) [ Designated as safety issue: Yes ]
  • Disease-free survival (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum tolerated dose (phase I) [ Designated as safety issue: Yes ]
  • Overall survival (phase II) [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2005
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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00293436

Locations
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Study Chair: Alan P. Venook, MD University of California, San Francisco
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00293436     History of Changes
Other Study ID Numbers: CDR0000458055, UCSF-04459, UCSF-H43059-26066-02
Study First Received: February 16, 2006
Last Updated: September 13, 2012
Health Authority: United States: Federal Government

Keywords provided by University of California, San Francisco:
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized resectable adult primary liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Celecoxib
Erlotinib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014