p53 Vaccine in Treating Patients With Adenocarcinoma of the Ovary Who Have Either No Evidence of Disease or Elevated Biomarkers - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00019903

Purpose

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of p53 vaccine therapy and to see how well it works in treating patients with adenocarcinoma of the ovary with either no evidence of disease or elevated biomarkers.

Condition	Intervention	Phase
Ovarian Cancer	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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low BurdenAdenocarcinoma of the Ovary

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Aldesleukin Sargramostim Freund's adjuvant

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as measured by Common Toxicity Criteria v2.0 at baseline and every 3 weeks [ Designated as safety issue: Yes ]
Tumor response as measured by CT scans at baseline and every 3 months [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	June 2000
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine whether endogenous cellular immunity to p53 vaccine is present in patients with adenocarcinoma of the ovary who have no evidence of disease or marker disease only and whether vaccination with these peptides can induce or boost the cellular immunity of these patients.
Determine the type and characteristics of the cellular immunity generated by this regimen in these patients.

Secondary

Determine the toxicity of this regimen in these patients.
Correlate any immunologic response with any objective tumor response to this regimen in these patients.

OUTLINE: All patients undergo apheresis prior to therapy, prior to every other course, and 1 month after the last course.

Patients are assigned to one of two treatment arms.

Arm I: Patients receive p53 vaccine and sargramostim (GM-CSF) emulsified with Montanide ISA-51 subcutaneously (SC) on day 1.
Arm II: Autologous peripheral blood mononuclear cells are harvested and selected for monocytes on day -6. The monocyte fraction is cultured with GM-CSF and interleukin-4 for 7 days and then pulsed with p53 vaccine. Patients receive p53 vaccine-pulsed autologous dendritic cells IV over 5 minutes on day 1.
Both arms: Vaccine treatment repeats every 3 weeks for 4 doses. During courses 3 and 4, patients receive interleukin-2 SC 5 days a week for 2 weeks beginning on day 3. Patients with stable or responding disease may continue vaccine treatment for up to 2 years. Patients who progress on the original p53 vaccine may receive mutant p53 vaccine administered as in Arm I, beginning 4-12 weeks after the original vaccine and continuing for up to 2 years.

Patients are followed at 1 month. Patients who are off therapy are followed every 2-4 months for 2 years.

PROJECTED ACCRUAL: A total of 45 patients (9-16 per treatment arm) will be accrued for this study within 2 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically proven adenocarcinoma of the ovary
- Marker only disease OR
- No evidence of disease post therapy for initial ovarian cancer (stage III, IV or recurrent)
HLA-A2.1 positive
Tumor tissue available for determination of p53 protein expression and genetic mutation
- p53 positive tumor by immunohistochemical analysis
No CNS metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0 or 1

Life expectancy:

More than 3 months

Hematopoietic:

Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 2.0 mg/dL
SGOT or SGPT no greater than 4 times normal
Hepatitis B surface antigen negative
Hepatitis C antibody negative

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

No New York Heart Association class III or IV heart disease
No myocardial infarction within past 6 months
No prior congestive heart failure
No prior ventricular arrhythmias or other arrhythmias requiring therapy

Immunologic:

No prior autoimmune disease including, but not limited to, the following:
- Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
- Systemic lupus erythematosus, Sjögren's syndrome, or scleroderma
- Myasthenia gravis
- Goodpasture's syndrome
- Addison's disease
- Hashimoto's thyroiditis
- Active Graves' disease
HIV negative
No underlying immune deficiency

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No second malignancy within past year except curatively treated carcinoma in situ of the cervix or basal cell skin cancer
No active infection requiring antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 4 weeks since prior immunotherapy and recovered
At least 1 year since prior bone marrow transplantation

Chemotherapy:

At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

At least 4 weeks since prior systemic steroids and recovered
No concurrent systemic steroids

Radiotherapy:

At least 4 weeks since prior radiotherapy and recovered

Surgery:

Not specified

Other:

Chronic suppressive antibiotics allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019903

Locations

United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Samir N. Khleif, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000067278, NCI-99-C-0137, NCI-NMOB-9903, NCI-T99-0074
Study First Received:	July 11, 2001
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00019903 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I ovarian epithelial cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-HIV Agents
Ovarian Neoplasms
Immunologic Factors
Antineoplastic Agents
Gonadal Disorders
Physiological Effects of Drugs
Adjuvants, Immunologic
Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Ovarian Diseases

Antiviral Agents
Pharmacologic Actions
Adnexal Diseases
Genital Diseases, Female
Neoplasms
Neoplasms by Site
Aldesleukin
Anti-Retroviral Agents
Therapeutic Uses
Freund's Adjuvant
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on November 09, 2009