Vaccine Therapy Plus Interleukin-2 in Treating Women With Stage IV, Recurrent, or Progressive Breast or Ovarian Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. It is not yet known whether combining vaccine therapy with interleukin-2 is effective in treating breast and ovarian cancer. PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy and interleukin-2 and to see how well they work in treating women with stage IV, recurrent, or progressive breast or ovarian cancer.

Detailed Description
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OBJECTIVES: Determine whether endogenous cellular immunity to the p53 peptide vaccine is present in patients with stage IV, recurrent, or progressive breast or ovarian cancer and whether vaccination with these peptides and low-dose interleukin-2 can induce or boost the cellular immunity in these patients. Determine the type and characteristics of cellular immunity generated by this regimen in these patients. 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: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment arms. All patients undergo apheresis of autologous peripheral blood mononuclear cells, which are harvested and selected for monocytes on day -6. The monocyte fraction is cultured with sargramostim (GM-CSF) and interleukin-4 for 7 days and then pulsed with p53 peptide vaccine. Arm I: Patients receive p53 peptide vaccine subcutaneously (SC) on day 1. Arm II: Patients receive p53 peptide vaccine IV over 5 minutes on day 1. Treatment in both arms repeats every 3 weeks for a total of 4 vaccinations (4 courses). During courses 3 and 4, patients also receive low-dose interleukin-2 (IL-2) SC daily on days 3-7 and days 10-14. Patients with stable or responding disease may continue to receive vaccine and IL-2 treatment for up to 2 years. Patients are followed at 1 month and then every 2-4 months for 2 years. PROJECTED ACCRUAL: A maximum of 34 patients will be accrued for this study within 2 years.

Official Title
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Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Adenocarcinoma of the Breast or Ovary

Conditions
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Breast Cancer, Ovarian Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Biological: p53 peptide vaccine
* Procedure: in vitro-treated peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast or ovary Stage IV, recurrent, or progressive disease with no chemotherapy or radiotherapy options available that would increase survival Tumor tissue available for determination of p53 protein expression and genetic mutation p53-positive tumor by immunohistochemical analysis HLA-A2.1 positive No prior CNS metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal status: Not specified 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: Must have positive intradermal delayed hypersensitivity test for 1 of the following: Mumps Trichophyton Tetanus Candida PPD No underlying immune deficiency 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 No active infection requiring antibiotics HIV negative Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other active malignancy within the past 2 years except curatively treated carcinoma in situ of the cervix or basal cell skin cancer 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: Prior anticancer hormonal therapy allowed At least 4 weeks since prior systemic steroids and recovered Radiotherapy: At least 4 weeks since prior radiotherapy and recovered Surgery: Not specified Other: Chronic suppressive antibiotics allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: p53 peptide vaccine|nan|
|Procedure: in vitro-treated peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cellular immunity as measured by Elipsot assay and 51 Cr-release assay at baseline, and every 3 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as measured by CTC v2.0 at baseline, and every 3 weeks |  |  | 
| Tumor response as measured by CT scan at baseline, and every 3 months |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer, recurrent ovarian epithelial cancer, stage IV ovarian epithelial cancer