Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	NCI-99-C-0137 NCI-NMOB-9903, NCI-T99-0074, T99-0074, NCT00019903

Objectives

Primary

1. 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.
2. Determine the type and characteristics of the cellular immunity generated by this regimen in these patients.

Secondary

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

Entry 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

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

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/mm³

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

Expected Enrollment

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

Outcomes

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
Tumor response as measured by CT scans at baseline and every 3 months

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Samir N. Khleif, MD, Principal investigator		Ph: 301-435-5392 Email: khleif@nih.gov

Registry Information
Official Title		Vaccine Therapy with Tumor Specific p53 Peptides in Adult Patients with Low BurdenAdenocarcinoma of the Ovary
Trial Start Date		2000-06-16
Trial Completion Date		2007-12-04
Registered in ClinicalTrials.gov		NCT00019903
Date Submitted to PDQ		1999-08-24
Information Last Verified		2007-01-08