Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001703
Status:
TERMINATED
Last Update Posted:
2014-07-25
First Post:
1999-11-03
Brief Title:
Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
Status:
TERMINATED
Status Verified Date:
2014-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to poor accrual and lack of peptide vaccine
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
About 27000 new cases of renal cell carcinoma RCC are diagnosed every year in the United States 11000 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 andor 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
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 andor 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
Detailed Description:
About 27000 new cases of renal cell carcinoma RCC are diagnosed every year in the United States 11000 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 andor 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
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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 98-C-0139 | OTHER | None | None |
| 98-C-0139 | OTHER | Clinical Center National Institutes of Health | None |