Gene Therapy in Treating Patients With Cancer of The Liver

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 1

Conditions: Liver Cancer

Treatments: Biological: Ad5CMV-p53 gene

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003147

CDR0000065932 (Registry Identifier)

NCI-2012-02259

NCI-T96-0059

PCI-96-035

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Biological: Ad5CMV-p53 gene