Celecoxib and Erlotinib in Treating Patients With Liver Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: erlotinib hydrochloride
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: erlotinib hydrochloride|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (phase I) |  |  | 
| Disease-free survival (phase II) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (phase I) |  |  | 
| Overall survival (phase II) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized resectable adult primary liver cancer