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)
18 Years
N/A
Both
Liver Cancer
Trial Information
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)
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Antoni Ribas, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000389221
NCT ID:
NCT00093548
Start Date:
Completion Date:
Related Keywords:
- Liver Cancer
- adult primary hepatocellular carcinoma
- advanced adult primary liver cancer
- localized resectable adult primary liver cancer
- localized unresectable adult primary liver cancer
- Liver Neoplasms
- Carcinoma, Hepatocellular
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