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

Jonsson Comprehensive Cancer Center

Status and phase

Withdrawn

Phase 2

Phase 1

Conditions

Liver Cancer

Treatments

Biological: alpha fetoprotein plasmid DNA vaccine

Biological: alpha fetoprotein adenoviral vector vaccine

Biological: sargramostim plasmid DNA hepatocellular carcinoma vaccine adjuvant

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00093548

CDR0000389221

UCLA-0302008-02

Details and patient eligibility

About

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.

Full description

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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