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Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma

NCT00001703 · Status: TERMINATED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 6

Last updated 2014-07-25

Study results available
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Summary

About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United States. 11,000 of these cases will die from the disease. More than half of patients present with advanced or metastatic disease for which chemotherapy plays a very limited role. Therefore, development of another therapeutic approach is needed. Cancers in humans are commonly associated with mutations in dominant and recessive oncogenes. These genes produce mutated proteins that are unique to cancer cells. Von Hipple-Lindau (VHL) gene which is associated with the development of the VHL disease, has been recently mapped and cloned, and it is found to be mutated in 57% of sporadic renal cell carcinomas.

Data in mice have shown the generation of major histocompatibility complex (MHC) restricted cytotoxic T lymphocyte (CTL) that are capable of detecting endogenous cytoplasmic peptide derived from mutated oncogenes. In addition, we have recently demonstrated, by conducting different phase I clinical trials in which we vaccinate cancer patients with mutated Ras or p53 peptides corresponding to the abnormality patients harbor in their tumors, that in some patients we can generate immunological responses represented by the generation of lymphocytes (CD4+ and/or CD8+). In the current study, we would like to extend our observations to test whether VHL tumor suppressor protein can be immunologically targeted by vaccination. We have identified specific epitopes along the amino acid sequence of the VHL protein, which represent known specific human leukocyte antigen (HLA) class-I binding motifs. These amino acids stretches in the VHL protein correspond to the area of the point mutation hot spots. Therefore, we propose to treat patients with sporadic RCC who carry VHL mutations in their tumors with corresponding mutant VHL peptide vaccination. This vaccination will be done either by using pulsed-autologous peripheral mononuclear cells with the peptides, or peptides administered subcutaneously alone or in combination with cytokines.

Conditions

Interventions

BIOLOGICAL

incomplete Freund's adjuvant

0.7 ml of ISA-51 (Montanide ISA-51 adjuvant, incomplete Freund's adjuvant) will be mixed with peptide alone and injected subcutaneously every four weeks for a total of four vaccinations.

BIOLOGICAL

von Hippel-Lindau peptide vaccine

1000 micrograms administered subcutaneously every four weeks for a total of four vaccinations.

Sponsors & Collaborators

  • National Cancer Institute (NCI)

    lead NIH

Principal Investigators

  • Samir N Khleif, M.D. · National Cancer Institute, National Institutes of Health

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
1998-08-31
Primary Completion
2008-11-30
Completion
2008-11-30

Countries

  • United States

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00001703 on ClinicalTrials.gov