p53 Vaccine for Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT00001827|
Recruitment Status : Terminated
First Posted : November 4, 1999
Last Update Posted : October 6, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Neoplasm||Biological: aldesleukin Biological: incomplete Freund's adjuvant Biological: p53 peptide vaccine Biological: sargramostim Biological: therapeutic autologous dendritic cells Procedure: in vitro-treated peripheral blood stem cell transplantation||Phase 2|
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 p53:264 - 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Masking:||None (Open Label)|
|Official Title:||Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary|
|Study Start Date :||July 26, 1999|
|Actual Primary Completion Date :||December 17, 2007|
|Actual Study Completion Date :||January 25, 2013|
- Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks.
- Toxicity as measured by Common Toxicity Criteria v2.0 at baseline and every 3 weeks.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001827
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Jay A Berzofsky, M.D.||National Cancer Institute (NCI)|