Vaccine Therapy in Treating Patients With Liver Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have liver cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of alpha-fetoprotein peptide-pulsed autologous dendritic cells in HLA-A*0201-positive patients with hepatocellular carcinoma. Determine the safety and toxicity of this regimen in these patients. Determine the immunological effects of this regimen in these patients. Determine the progression-free survival and clinical responses in patients treated with this regimen. OUTLINE: This is a dose-escalation study. Patients receive alpha-fetoprotein peptide-pulsed autologous dendritic cells intradermally on day 1. Treatment repeats every 2 weeks for a total of 3 doses in the absence of unacceptable toxicity. Cohorts of 3-12 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 2 of 12 patients experience dose-limiting toxicity. Patients are followed at weeks 1, 4, and 12 and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

Official Title
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A Phase I/II Trial Testing Immunization With Dendritic Cells Pulsed With Four AFP Peptides in Patients With Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Biological: AFP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HLA-A*0201 positive adults over the age of 18. Have HCC with a serum AFP determination >30ng/ml. Both male and female patients may be enrolled. Karnofsky Performance Status greater than or equal to 70 percent. No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease. No previous evidence of opportunistic infection. Adequate baseline hematological function as assessed by the following laboratory values with 30 days prior to study entry: Hemoglobin >9.0g/dl Platelets >50000/mm3 Absolute Neutrophil Count >1,000/mm3 Child-Pugh Class A or B for chronic liver disease. Ability to give informed consent. Exclusion Criteria: Any congenital or acquired condition leading to inability to generate an immune response, including concomitant immune suppressive therapy. Concomitant steroid therapy or chemotherapy, or any of these other treatments < 30 days before the first vaccination. Females of child-bearing potential must have negative serum beta-HCG pregnancy test (within Day -14 to Day 0). Acute infection: any acute viral, bacterial, or fungal infection, which requires specific therapy. Acute therapy must have been completed within 14 days prior to study treatment. HIV-infected patients. Patients with any underlying conditions which would contraindicate therapy with study treatment. Patients with organ allografts. O2 sat <91% on room air; dyspnea at rest.

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: Treatment<br>See intervention description. | Biological: AFP<br>* Increasing doses of AFP will be given to groups of 3 intradermally. Subjects will receive 3 biweekly vaccinations. At least 2 patients at a given dose must have received their complete 3 vaccination schedule with a 30 day observation period after the last vaccination before a higher dose is initiated.<br>* Other names: AFP peptide-pulsed autologous DC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity and maximum tolerable dose. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Generation of AFP specific immunity. |  | 3 years | 
| Progression-free survival. |  | 3 years | 
| clinical response in patients with measurable disease. |  | 3 years | 

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