Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

Sponsor

Lisa H. Butterfield, Ph.D. (Other)

Overall Status

Terminated

CT.gov ID

NCT00669136

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

Patient Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the safety, toxicity and immunological effects of adjuvant administration of an experimental therapy consisting on priming with three intramuscular administrations of a plasmid expressing human AFP (phAFP) together with a plasmid expressing human GM-CSF (phGM-CSF), followed by a single intramuscular boost with an AFP adenoviral vector (AdVhAFP) to patients with locoregionally pre-treated hepatocellular carcinoma (HCC).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Hepatoma Liver Cancer, Adult Liver Cell Carcinoma Liver Cell Carcinoma, Adult Cancer of Liver Cancer of the Liver Cancer, Hepatocellular Hepatic Cancer Hepatic Neoplasms Hepatocellular Cancer Liver Cancer Neoplasms, Hepatic Neoplasms, Liver	Drug: AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Trial Testing Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost	Drug: AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost

Arm

Intervention/Treatment

Other: 1

AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost

Drug: AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost

AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity (DLT) and Phase II Recommended Dose (P2RD) [6 months]
Immunological response rate in PBMC as indicated by the ELISPOT assay [6 months]

Secondary Outcome Measures

Disease-Free Survival (DFS) [six months]
Immunological response rate as indicated by optional DTH [six months]
Immunological response rate in PBMC as indicated by the tetramer assay [six months]
Immunological response rate in lymph nodes as indicated by the ELISPOT assay [six months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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 AdV boost).