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

Phase 1/Phase 2
18 Years
Not Enrolling
Liver Cancer

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Trial Information

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



- 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)


- 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

After completion of study treatment, patients are followed periodically.

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

Inclusion Criteria


- 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

- History of vascular invasion (macro or micro)

- History of poorly differentiated HCC

- Underlying cirrhosis

- No Child-Pugh class C cirrhosis


- 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

- 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


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety (phase I)

Safety Issue:


Principal Investigator

Alan P. Venook, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Federal Government

Study ID:




Start Date:

January 2005

Completion Date:

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • advanced adult primary liver cancer
  • localized resectable adult primary liver cancer
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



UCSF Comprehensive Cancer CenterSan Francisco, California  94115