Gene Therapy in Treating Patients With Cancer of The Liver

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of gene therapy with the p53 gene in treating patients who have cancer of the liver that cannot be surgically removed. Inserting the p53 gene into a person's tumor may improve the body's ability to fight liver cancer.

Detailed Description
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OBJECTIVES: I. Determine the safety of adenovirus p53 construct (adeno-p53) in patients with hepatocellular carcinoma. II. Investigate the potential effects of intralesional adeno-p53 given by monthly percutaneous injections in these patients. OUTLINE: This is a dose escalation, multicenter study. Patients receive adenovirus p53 construct by percutaneous injection to a maximum of two lesions on day 1. Treatment is repeated every 28 days for up to 6 courses. In the absence of dose-limiting toxicity (DLT) in the first cohort of 6 patients treated, subsequent cohorts of 6 patients each receive escalating doses of the drug on the same schedule. If DLT occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and that dose is declared the maximum tolerated dose. Study treatment may continue in the absence of disease progression and unacceptable adverse events.

Official Title
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Phase I Study of Percutaneous Injections of Adeno-Virus p53 Construct (ADENO-p53) for Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Biological: Ad5CMV-p53 gene


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed unresectable hepatocellular carcinoma (HCC) or highly suspicious for HCC based on CT scan and elevated alfafetoprotein Measurable disease by abdominal CT scan Accessible (peripheral) lesions No metastatic disease PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Platelet count at least 60,000/mm3 Absolute neutrophil count greater than 1,500/mm3 Prothrombin time of no greater than 16 seconds after administration of fresh frozen plasma Bilirubin no greater than 3.0 mg/dL Creatinine less than 1.5 mg/dL Child's class A or B cirrhosis eligible No uncontrolled infection Not pregnant or breast feeding No unstable or severe intercurrent medical condition PRIOR CONCURRENT THERAPY: At least 4 weeks since prior chemotherapy At least 4 weeks since prior radiation therapy No prior hepatic transplantation No more than 1 prior systemic regimen for hepatocellular carcinoma allowed No concurrent therapy with other investigational agents No prior gene therapy No prior intralesional 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive adenovirus p53 construct by percutaneous injection to a maximum of two lesions on day 1. Treatment is repeated every 28 days for up to 6 courses. In the absence of dose-limiting toxicity (DLT) in the first cohort of 6 patients treated, subsequent cohorts of 6 patients each receive escalating doses of the drug on the same schedule. If DLT occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and that dose is declared the maximum tolerated dose. Study treatment may continue in the absence of disease progression and unacceptable adverse events. | Biological: Ad5CMV-p53 gene<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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