Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: incomplete Freund's adjuvant; von Hippel-Lindau peptide vaccine
Intervention description: 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.; 1000 micrograms administered subcutaneously every four weeks for a total of four vaccinations.
Intervention MeSH terms: Freund's Adjuvant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Kidney; Genes; Vaccine Therapy; Renal Cell Carcinoma

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.
    

Eligibility criteria:

        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.