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

NCT00669136 | Terminated Phase 1 DMC

• 2 other identifiers: 04-101R01CA104524
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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).

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (1)

1

OTHER

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

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

Interventions

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

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

1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients who meet any one of the following criteria will be excluded from study entry:
• 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).

Sponsors & Collaborators

• Lisa H. Butterfield, Ph.D.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of California

Los Angeles, California, 90095, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• James Pingpank, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Surgery and Immunology

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 29, 2008
• Study Start: June 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: December 3, 2015

Record last verified: 2015-12

Locations

US (2)