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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00669136
Recruitment Status : Terminated (Poor accrual and limited target patient population for future accrual. Did not complete the Phase 1 portion of the trial.)
First Posted : April 29, 2008
Last Update Posted : December 3, 2015
Information provided by (Responsible Party):

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  (Clinical Trial)
Actual Enrollment : 2 participants
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 : June 2009
Primary Completion Date : March 2013
Study Completion Date : March 2013
Arms and Interventions

Arm Intervention/treatment
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 :
  1. Dose Limiting Toxicity (DLT) and Phase II Recommended Dose (P2RD) [ Time Frame: 6 months ]
  2. Immunological response rate in PBMC as indicated by the ELISPOT assay [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Disease-Free Survival (DFS) [ Time Frame: six months ]
  2. Immunological response rate as indicated by optional DTH [ Time Frame: six months ]
  3. Immunological response rate in PBMC as indicated by the tetramer assay [ Time Frame: six months ]
  4. Immunological response rate in lymph nodes as indicated by the ELISPOT assay [ Time Frame: six months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00669136

United States, California
University of California
Los Angeles, California, United States, 90095
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Lisa H. Butterfield, Ph.D.
National Cancer Institute (NCI)
Principal Investigator: James Pingpank, MD University of Pittsburgh
More Information

Responsible Party: Lisa H. Butterfield, Ph.D., Professor of Medicine, Surgery and Immunology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00669136     History of Changes
Other Study ID Numbers: 04-101
R01CA104524 ( U.S. NIH Grant/Contract )
First Posted: April 29, 2008    Key Record Dates
Last Update Posted: December 3, 2015
Last Verified: December 2015

Keywords provided by Lisa H. Butterfield, Ph.D., University of Pittsburgh:
AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost
AFP Immunization

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Immunologic Factors
Physiological Effects of Drugs