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

Phase 2
18 Years
Not Enrolling
Renal Cell Carcinoma

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Trial Information

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

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 gene, which is
associated with the development of the VHL disease, has been recently mapped and cloned; it
is found to be mutated in 57% of sporadic renal cell carcinomas.

Data in mice have shown the generation of MHC restricted 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 HLA class-I binding
motifs. These amino acids stretches in the VHL protein correspond to the area of the point
mutation hot spots. Therefore, this protocol treats patients with sporadic RCC who carry
VHL mutations in their tumors with corresponding mutant VHL peptide vaccination.

Inclusion Criteria:

- Patients must be 18 years of age or older.

- Histologic diagnosis of renal cell carcinoma.

- Tumor tissue availability for determination of Von Hippel-Lindau (VHL) mutation
(paraffin block, or fresh tissue).

- Patients must carry a VHL mutation in their tumor.

- Patients must have metastatic disease for which no further chemotherapy or radiation
options, which are known to increase survival, are available.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

- Expected survival more than 3 months.

- While measurable disease is preferable, it is not a necessity.

- The patient should not have received chemotherapy, radiation therapy, immunotherapy
or steroids for at least 4 weeks prior to starting vaccination, and should have
recovered from all acute toxicities of previous treatment.

- Patients must understand and sign an informed consent document that explains the
neoplastic nature of his/her disease, the procedures to be followed, the experimental
nature of the treatment, alternative treatments, and potential risks and toxicities.

Exclusion Criteria:

- Any condition that does not fit with the inclusion criteria.

- Any of the following: White blood cells (WBC) less than 2000/mm(3); Platelets less
than 100K/mm

- (3); Creatinine greater than 2.0 mg/dl; Serum Bilirubin greater than 2.0 mg/dl, Serum
glutamic oxaloacetic transaminase (SGOT), or Serum glutamic pyruvic transaminase
(SGPT) greater than 4x normal.

- Human Immunodeficiency virus (HIV) or active Hepatitis B or C (i.e. detectable
Hepatitis B surface (HBS) Antigen or Heteroconjugate (HC) antibodies).

- Pregnant women or nursing mothers are ineligible. Women with reproductive potential
must have negative urine pregnancy test. Women of reproductive potential must use
adequate contraception.

- Patients with active ischemic heart disease (i.e. Class III or IV cardiac
disease)-New York Heart Association), a recent history of myocardial infarction
(within the last 6 months), history of congestive heart failure, ventricular
arrhythmias or other arrhythmias requiring therapy, or any other medical conditions
that the principal investigators sees to be unfit for such therapy.

- History of Central Nervous System (CNS) metastases.

- Patients with history of autoimmune disease e.g. (autoimmune neutropenia,
thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren
syndrome, or scleroderma; myasthenia grave's; Good pasture syndrome; Addison's
disease, Hashimoto's thyroiditis, rheumatoid arthritis, multiple sclerosis, or active
Graves' disease).

- If, in the opinion of the principal or associate investigators, it is not in the best
medical interest of the patient to enter this study, the patient will be ineligible.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of Participants Who Generated an Immune Response

Outcome Description:

The immunological response was assessed by in-vitro T cell cytokine production enzyme-linked immunosorbent spot (ELISPOT). From each patients, post-vaccination peripheral blood mononuclear cells (PBMC) were compared to pre-vaccination as a baseline. A positive ELISPOT result for the patients was defined as a total number of experimental spots in the post-vaccination sample of more than twofold above the total spots in the pre-vaccination sample.

Outcome Time Frame:

30 months

Safety Issue:


Principal Investigator

Samir N Khleif, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health


United States: Federal Government

Study ID:




Start Date:

August 1998

Completion Date:

November 2008

Related Keywords:

  • Renal Cell Carcinoma
  • Immunotherapy
  • Kidney
  • Genes
  • Vaccine Therapy
  • Renal Cell Carcinoma
  • Carcinoma
  • Carcinoma, Renal Cell



National Cancer Institute, National Institutes of Health Bethesda, Maryland  20892