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

Recruiting in Palo Alto (17 mi)

Overseen bySamir N Khleif, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?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

Histologic diagnosis of renal cell carcinoma.

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.

+7 more

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Group A-VHL peptide and ISA-51 adjuvantExperimental Treatment2 Interventions

Patients are vaccinated with 1000 micrograms of the mutant Von Hipple-Lindau (VHL) peptide administered subcutaneously along with ISA-51 adjuvant (Montanide ISA-51 adjuvant, Incomplete Freund's adjuvant) and injected subcutaneously every four weeks for a total of four vaccinations.