Ignite Creation Date:
2024-05-05 @ 9:53 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001827
Status:
TERMINATED
Last Update Posted:
2017-10-06
First Post:
1999-11-03
Brief Title:
p53 Vaccine for Ovarian Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary
Status:
TERMINATED
Status Verified Date:
2013-01-25
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine whether vaccination with a p53 peptide can boost an immune response to ovarian cancer and what the side effects are of the vaccine
Many patients with ovarian cancer have an altered mutated gene called p53 that causes the production of abnormal proteins found in their tumor cells The body s immune system may try unsuccessfully to fight these abnormal proteins In this study ovarian cancer patients with a p53 abnormality will be vaccinated with a p53 peptide a part of the same abnormal protein found in their tumor to try to boost their body s immune response to the cancer
Patients will be divided into two groups Group A will have four p53 peptide vaccinations three weeks apart injected under the skin The injection will include a drug called ISA-51 which increases the effect of the vaccine This group will also receive two other drugs that boost the immune system IL-2 and GM-CSF Group B will have four p53 peptide vaccinations three weeks apart The peptide will be mixed with the patient s own blood cells and infused into a vein This group will also receive IL-2 but not GM-CSF
All study candidates will be tested to see if their cancer has a p53 abnormality and if their immune system mounted a defense against it These tests may include a tumor biopsy removal of a small part of the tumor for microscopic examination lymphapheresis a procedure to take blood remove white blood cells called lymphocytes and return the red cells and an immune response test similar to a skin test for tuberculosis During the study patients will have additional skin tests and blood tests
Many patients with ovarian cancer have an altered mutated gene called p53 that causes the production of abnormal proteins found in their tumor cells The body s immune system may try unsuccessfully to fight these abnormal proteins In this study ovarian cancer patients with a p53 abnormality will be vaccinated with a p53 peptide a part of the same abnormal protein found in their tumor to try to boost their body s immune response to the cancer
Patients will be divided into two groups Group A will have four p53 peptide vaccinations three weeks apart injected under the skin The injection will include a drug called ISA-51 which increases the effect of the vaccine This group will also receive two other drugs that boost the immune system IL-2 and GM-CSF Group B will have four p53 peptide vaccinations three weeks apart The peptide will be mixed with the patient s own blood cells and infused into a vein This group will also receive IL-2 but not GM-CSF
All study candidates will be tested to see if their cancer has a p53 abnormality and if their immune system mounted a defense against it These tests may include a tumor biopsy removal of a small part of the tumor for microscopic examination lymphapheresis a procedure to take blood remove white blood cells called lymphocytes and return the red cells and an immune response test similar to a skin test for tuberculosis During the study patients will have additional skin tests and blood tests
Detailed Description:
P53 is the most commonly mutated gene in human cancers it has been found to be mutated in almost 50 of ovarian cancers Genetic mutation of p53 results in stabilization and increase in the level of the protein In some cases overexpression of p53 protein could also occur in tumors without detectable mutation in the open reading frame Therefore p53 could function as an antigen through two different mechanisms as a mutant foreign protein and as a selfoverexpressed protein The p53264 - 272 wild type peptide has been shown to have high affinity for HLA-A2 It has also been shown to be naturally processed and endogenously
presented by HLA-A2 in different types of tumor cell lines for CTL recognition These CTL
were able to lyse tumor cells overexpressing wild type or mutant p53 protein and failed to lyse
normal cells expressing normal levels of wild type p53
In this protocol we will be vaccinating HLA-A2 ovarian cancer patients who carry tumors which overexpress p53 with the wild type p53 peptide 264-272 This will be given either subcutaneously admixed with ISA-51 and GM-CSF adjuvants or intravenously pulsed on dendritic cells along with low dose subcutaneous IL-2 In addition those patients who express mutant p53 may also be vaccinated with a mutant p53 peptide which corresponds to the mutation they harbor in their tumor should the patients progress on the p53 264-272 peptide
presented by HLA-A2 in different types of tumor cell lines for CTL recognition These CTL
were able to lyse tumor cells overexpressing wild type or mutant p53 protein and failed to lyse
normal cells expressing normal levels of wild type p53
In this protocol we will be vaccinating HLA-A2 ovarian cancer patients who carry tumors which overexpress p53 with the wild type p53 peptide 264-272 This will be given either subcutaneously admixed with ISA-51 and GM-CSF adjuvants or intravenously pulsed on dendritic cells along with low dose subcutaneous IL-2 In addition those patients who express mutant p53 may also be vaccinated with a mutant p53 peptide which corresponds to the mutation they harbor in their tumor should the patients progress on the p53 264-272 peptide
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 |
|---|---|---|---|
| 99-C-0137 | None | None | None |