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Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary

Phase 2
18 Years
Not Enrolling
Ovarian Neoplasm

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Trial Information

Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary

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

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)

Inclusion Criteria


Patients must be 18 years of age or older.

Histologic diagnosis of adenocarcinoma of the ovary.

Tumor tissue availability for determination of p53 protein expression and genetic mutation
(paraffin block, or fresh tissue).

Immunohistochemical analysis of the tumor must demonstrate positive p53 staining.

Patients should have ovarian cancer with marker only disease or patients with stage III,
IV or recurrent who are NED post therapy.

ECOG performance status of 1 or 0.

Expected survival of more than 3 months.

The patients should not have received chemotherapy, radiation therapy, immunotherapy or
systemic doses of steroids for at least 4 weeks prior to starting vaccination. And the
patient should have recovered from all acute toxicities of previous treatment. Patients
who received bone marrow transplantation within a year will not be eligible for the trial.

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.

Patients should have HLA-A2.1 haplotype.


Any condition that does not fit with the eligibility criteria.

Any of the following:

Platelets less than 100K/mm(3)

Creatinine greater than 2.0 mg/dl

Serum Bilirubin greater than 2.0 mg/dl, SGOT, or SGPT greater than 4 times normal

HIV or Hepatitis B or C (i.e. detectable HBS Antigen or HC Ab) since these conditions
might have an effect on the immune system.

Pregnant women or nursing mothers are ineligible since the effect of this investigational
treatment on the health of the embryo is not known. Women with reproductive potential
must have negative pregnancy test and 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 arrythmias or other arrythmias requiring

Second malignancy (within the past 2 years) other than curatively treated carcinoma
in-situ of cervix or basal cell carcinoma of the skin. These patients will be excluded
for the possibility of the existence of a different mutation in the other primary

History of CNS metastases.

Patients with underlying immune deficiency or history of autoimmune disease e.g.
(autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus
erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome;
Addison's disease, Hashimoto's thyroiditis, active Graves' disease, or other diseases
which qualify as autoimmune in origin).

Patients with active infections requiring antibiotics. Patients requiring chronic
suppressive antibiotics will be eligible for the trial.

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.

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks.

Safety Issue:


Principal Investigator

Steven A Rosenberg, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

July 1999

Completion Date:

January 2013

Related Keywords:

  • Ovarian Neoplasm
  • Immunotherapy
  • Cancer
  • Oncogenes
  • T-cells
  • Vaccine Therapy
  • p53 Peptide
  • Ovarian Cancer
  • Neoplasms
  • Ovarian Neoplasms



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892