RATIONALE: Inserting the p53 gene into a person's tumor may improve the body's ability to fight liver cancer.

PURPOSE: Phase I trial to study the effectiveness of gene therapy with the p53 gene in treating patients with cancer of the liver that cannot be surgically removed.

Condition	Treatment or Intervention	Phase
adult primary hepatocellular carcinoma localized unresectable adult primary liver cancer	Drug: adenovirus p53	Phase I

Further Study Details: 

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.

PROTOCOL 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.

PROJECTED ACCRUAL: Up to 30 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 4 weeks since prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 4 weeks since prior radiation therapy
• Surgery: No prior hepatic transplantation
• Other: 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

--Patient Characteristics--

• Age: Over 18
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: 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
• Hepatic: Bilirubin no greater than 3.0 mg/dL
• Renal: Creatinine less than 1.5 mg/dL
• Other: Child's class A or B cirrhosis eligible; No uncontrolled infection; Not pregnant or breast feeding; No unstable or severe intercurrent medical condition

New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
Pennsylvania
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213,  United States

Study chairs or principal investigators

Chandra Prakash Belani,  Study Chair,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000065932; PCI-96-035; NCI-T96-0059
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  April 6, 2000
ClinicalTrials.gov Identifier:  NCT00003147
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08