Vaccine Therapy in Treating Patients With Liver Cancer

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

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.

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.

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:

  1. Hemoglobin >9.0g/dl
  2. Platelets >50000/mm3
  3. 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.