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

This study has been terminated.
(Poor accrual and limited target patient population for future accrual)
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00669136
First received: April 25, 2008
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Liver Cancer
Drug: AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) and Phase II Recommended Dose (P2RD) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Immunological response rate in PBMC as indicated by the ELISPOT assay [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease-Free Survival (DFS) [ Time Frame: six months ] [ Designated as safety issue: No ]
  • Immunological response rate as indicated by optional DTH [ Time Frame: six months ] [ Designated as safety issue: No ]
  • Immunological response rate in PBMC as indicated by the tetramer assay [ Time Frame: six months ] [ Designated as safety issue: No ]
  • Immunological response rate in lymph nodes as indicated by the ELISPOT assay [ Time Frame: six months ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: June 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669136

Locations
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
University of Pittsburgh
Investigators
Principal Investigator: James Pingpank, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00669136     History of Changes
Other Study ID Numbers: 04-101, R01 CA104524
Study First Received: April 25, 2008
Last Updated: June 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost
AFP Immunization

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma

ClinicalTrials.gov processed this record on August 28, 2014