Vaccine Therapy in Treating Patients With Liver Cancer

A Phase I/II Trial Testing Immunization With Dendritic Cells Pulsed With Four AFP Peptides in Patients With Hepatocellular Carcinoma

RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have liver cancer.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Biological: AFP

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of alpha-fetoprotein peptide-pulsed autologous dendritic cells in HLA-A*0201-positive patients with hepatocellular carcinoma.
• Determine the safety and toxicity of this regimen in these patients.
• Determine the immunological effects of this regimen in these patients.
• Determine the progression-free survival and clinical responses in patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive alpha-fetoprotein peptide-pulsed autologous dendritic cells intradermally on day 1. Treatment repeats every 2 weeks for a total of 3 doses in the absence of unacceptable toxicity.

Cohorts of 3-12 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 2 of 12 patients experience dose-limiting toxicity.

Patients are followed at weeks 1, 4, and 12 and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HLA-A*0201 positive adults over the age of 18.
• Have HCC with a serum AFP determination >30ng/ml.
• Both male and female patients may be enrolled.
• Karnofsky Performance Status greater than or equal to 70 percent.
• No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease.
• No previous evidence of opportunistic infection.

• Adequate baseline hematological function as assessed by the following laboratory values with 30 days prior to study entry:

  1. Hemoglobin >9.0g/dl
  2. Platelets >50000/mm3
  3. Absolute Neutrophil Count >1,000/mm3
• Child-Pugh Class A or B for chronic liver disease.
• Ability to give informed consent.

Exclusion Criteria:

• Any congenital or acquired condition leading to inability to generate an immune response, including concomitant immune suppressive therapy.
• Concomitant steroid therapy or chemotherapy, or any of these other treatments < 30 days before the first vaccination.
• Females of child-bearing potential must have negative serum beta-HCG pregnancy test (within Day -14 to Day 0).
• Acute infection: any acute viral, bacterial, or fungal infection, which requires specific therapy. Acute therapy must have been completed within 14 days prior to study treatment.
• HIV-infected patients.
• Patients with any underlying conditions which would contraindicate therapy with study treatment.
• Patients with organ allografts.
• O2 sat <91% on room air; dyspnea at rest.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; See intervention description.	Biological: AFP; Increasing doses of AFP will be given to groups of 3 intradermally. Subjects will receive 3 biweekly vaccinations. At least 2 patients at a given dose must have received their complete 3 vaccination schedule with a 30 day observation period after the last vaccination before a higher dose is initiated.; Other Names: AFP peptide-pulsed autologous DC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose limiting toxicity and maximum tolerable dose.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Generation of AFP specific immunity.	3 years
Progression-free survival.	3 years
clinical response in patients with measurable disease.	3 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: James S. Economou, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: advanced adult primary liver cancer; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer; localized resectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: CDR0000068806; UCLA-0001026; NCI-G01-1997