Vaccine Therapy in Treating Patients With Stage II, Stage IIIA, Stage IIIB, or Stage IVA Liver Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from DNA and a gene-modified virus may make the body build an immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of liver cancer. PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy and to see how well it works in treating patients with stage II, stage IIIA, stage IIIB, or stage IVA liver cancer.

Detailed Description
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OBJECTIVES: Primary Determine the dose-limiting toxicity and maximum tolerated dose of adjuvant vaccination comprising alpha fetoprotein (AFP) plasmid DNA and sargramostim (GM-CSF) plasmid DNA followed by AFP adenoviral vector boost in patients with HLA-A*0201-expressing stage II-IVA hepatocellular carcinoma. Secondary Determine the optimal biological dose of this regimen, as defined by the generation of AFP-specific immunity, in these patients. Determine disease-free survival of patients treated with this regimen. OUTLINE: This is a dose-escalation study of alpha fetoprotein (AFP) adenoviral vector boost. Patients receive vaccination comprising AFP plasmid DNA and sargramostim (GM-CSF) plasmid DNA intramuscularly (IM) on days 1, 30, and 60 in the absence of unacceptable toxicity. Patients then receive boost immunization comprising AFP adenoviral vector IM and intradermally on day 90. Cohorts of 3-6 patients receive escalating doses of AFP adenoviral vector boost until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed monthly for 3 months and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

Official Title
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A Phase I/II Trial Testing Immunization With AFP + GM-CSF Plasmid Prime And AFP Adenoviral Vector Boost In Patients With Hepatocellular Carcinoma (AFP Prime-Boost Protocol)

Conditions
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Liver Cancer

Intervention / Treatment
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* Biological: alpha fetoprotein adenoviral vector vaccine
* Biological: alpha fetoprotein plasmid DNA vaccine
* Biological: sargramostim plasmid DNA hepatocellular carcinoma vaccine adjuvant


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of hepatocellular carcinoma Stage II-IVA disease No active disease after local or regional therapy (e.g., surgical resection, radiofrequency ablation, cryoablation, or ethanol injection) Serum alpha fetoprotein > upper limit of normal HLA-A*0201 positive by DNA subtyping PATIENT CHARACTERISTICS: Age Over 18 Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Hemoglobin > 9.0 g/dL (transfusion independent) Platelet count > 50,000/mm^3 Absolute neutrophil count > 1,000/mm^3 Hepatic Child Pugh class A or B liver function Hepatitis B or C viral infection allowed Renal Not specified Cardiovascular No New York Heart Association class III or IV cardiac insufficiency No coronary artery disease Immunologic HIV negative No other acute viral, bacterial, or fungal infection requiring therapy No allergy to study agents No history of opportunistic infection No high serum titer of neutralizing anti-adenoviral antibodies No congenital or acquired condition resulting in an inability to generate an immune response Other Not pregnant Negative pregnancy test Fertile patients must use effective double-method (including a barrier method) contraception No other condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 30 days since prior chemotherapy No concurrent cytotoxic chemotherapy Endocrine therapy At least 30 days since prior steroid therapy No concurrent steroid therapy, including corticosteroids Radiotherapy Not specified Surgery See Disease Characteristics No prior organ allograft Other At least 2 weeks since prior therapy for acute infection No concurrent immunosuppressive therapy No concurrent cyclosporine

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: alpha fetoprotein adenoviral vector vaccine|nan|
|Biological: alpha fetoprotein plasmid DNA vaccine|nan|
|Biological: sargramostim plasmid DNA hepatocellular carcinoma vaccine adjuvant|nan|

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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adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized resectable adult primary liver cancer, localized unresectable adult primary liver cancer