A Phase I/II Trial Testing Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma
Eligible patients must have locoregionally treated HCC and have a prior AFP serum
determination over the limit of normality for each laboratory.
- This study will enroll adults over the age of 18.
- Have had HCC with a history of serum AFP determination above the upper limit of
normality for each laboratory.
- Both male and female patients may be enrolled. Premenopausal females who have not
undergone a surgical sterilization procedure must have a negative pregnancy test
prior to treatment. Sexually active females of child-bearing potential are required
to use two forms of contraception, including a barrier method, for trial eligibility.
Sexually active males should use an appropriate "double barrier" method of birth
control (such as female use of a diaphragm, intrauterine device (IUD), or
contraceptive sponge, in addition to male use of a condom.
- Be HLA-A2.1 positive (HLA-A*0201) by DNA subtyping, or HLA-A2 positive by flow
cytometry with antibodies MA2.1 and BB7.2.
- Stage II to IVa HCC after locoregional therapy (surgical resection, radio-frequency
ablation, cryoablation, ethanol injection, chemoembolization and radioembolization).
- Karnofsky Performance Status greater than or equal to 70 percent.
- No evidence of opportunistic infection in the year before enrollment.
- Adequate baseline hematological function as assessed by the following laboratory
values within 30 days prior to study entry (day -30 to 0):
Hemoglobin > 9.0 g/dL (patients cannot be transfusion dependent) Platelets > 50,000/mm3
Absolute Neutrophil Count (ANC) > 1,000/mm3
- Conserved liver function with a Child-Pugh Class A or B.
- Ability to give informed consent.
Patients who meet any one of the following criteria will be excluded from study entry:
- Any congenital or acquired condition leading to inability to generate an immune
response, including concomitant immune suppressive therapy. The ability to adequately
respond to recall skin test antigens will be tested before trial entry but a negative
response to skin allergens will not be reason for exclusion.
- Concomitant steroid therapy or chemotherapy, or any of these treatments < 30 days
before the first vaccination.
- Females of child-bearing potential (premenopausal and not surgically sterilized) must
have a negative serum HCG pregnancy test (within Day 14 to Day 0).
- Acute infection: any acute viral, bacterial, or fungal infection, which requires
specific therapy excluding HBV or HCV. Acute therapy must have been completed within
14 days prior to study treatment.
- HIV-infected patients (their ability to generate a cellular immune response is
altered due to the CD4-dependent immunosuppressive effects of the HIV infection).
- Patients with any underlying conditions which would contraindicate therapy with study
treatment (or allergies to reagents used in this study).
- Patients with organ allografts (they require prolonged immunosuppressive therapy).
- Patients with high serum titers of neutralizing anti-adenoviral antibodies (positive
at greater than 1:128 dilution by serum AdV blocking assay, expected to be
approximately 30% of patients, they have a greatly reduced ability to respond to the