Vaccine Therapy in Treating Patients With Recurrent Prostate Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well vaccine therapy works in treating patients with recurrent prostate cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the T-lymphocyte immune response in patients with recurrent adenocarcinoma of the prostate treated with prostate-specific antigen (PSA) peptide vaccine (PSA-3A; PSA: 154-163 [155L]) emulsified in Montanide ISA-51. SECONDARY OBJECTIVES: I. Determine the toxicity of this vaccine in these patients. II. Determine the effect of this vaccine on serum PSA level in these patients. OUTLINE: This is a pilot study. Patients receive prostate-specific antigen (PSA) peptide vaccine (PSA-3A; PSA: 154-163 [155L]) emulsified in Montanide ISA-51 subcutaneously once in weeks 0, 2, 4, 6, 10, 14, and 18 in the absence of disease progression* or unacceptable toxicity. NOTE: *A rise in PSA alone is not considered disease progression. After completion of study treatment, patients are followed at 1 and 4 weeks.

Official Title
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A Phase 2 Study of Prostate Specific Antigen Peptide 3A (PSA: 154-163(155L) ) (NSC # 722932, IND#9787) With Montanide ISA-51(NSC #675756, IND #9787) or Montanide® ISA 51 VG (NSC 737063) Vaccination in Prostate Cancer Recurrent

Conditions
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Adenocarcinoma of the Prostate, Recurrent Prostate Cancer

Intervention / Treatment
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* Biological: PSA:154-163(155L) peptide vaccine
* Biological: incomplete Freund's adjuvant
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate Must have undergone radical prostatectomy ≥ 3 months ago Prostate-specific antigen (PSA) level ≥ 0.6 ng/mL and rising (after radical prostatectomy) on ≥ 2 measurements separated by ≥ 3 months HLA-A2-positive peripheral blood mononuclear cells by flow cytometry No clinical evidence of local recurrence No palpable induration or mass in prostatic fossa No metastatic prostate cancer No osseous metastases by bone scan Performance status - ECOG 0-1 Performance status - Karnofsky 70-100% More than 1 year WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 AST and ALT ≤ 2.5 times upper limit of normal Bilirubin normal Hepatitis B and C negative Creatinine normal Creatinine clearance ≥ 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study PSA peptide vaccine or Montanide ISA-51 No history of systemic autoimmune disease or autoimmune disease requiring anti-inflammatory or immunosuppressive therapy Patients with history of autoimmune thyroiditis are eligible provided the patient requires only thyroid hormone replacement therapy AND disease has been stable for ≥ 1 year No known HIV positivity No ongoing or active infection No primary or secondary immune deficiency No psychiatric illness or social situation that would preclude study compliance No history of other uncontrolled illness No prior chemotherapy No prior hormonal therapy No concurrent systemic or ocular steroid therapy, except for any of the following: Inhaled steroids for asthma Limited topical steroids Replacement doses of cortisone More than 4 weeks since prior radiotherapy No prior radiotherapy to the prostate Prior radiotherapy to the pelvis after radical prostatectomy allowed See Disease Characteristics No other concurrent investigational agents No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive PSA peptide vaccine (PSA-3A; PSA: 154-163 [155L]) emulsified in Montanide ISA-51 subcutaneously once in weeks 0, 2, 4, 6, 10, 14, and 18 in the absence of disease progression or unacceptable toxicity. | Biological: PSA:154-163(155L) peptide vaccine<br>* Given subcutaneously<br>* Other names: PSA-3A;Biological: incomplete Freund's adjuvant<br>* Given subcutaneously<br>* Other names: Montanide ISA 51;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in frequency of CD8 T-lymphocyte precursors in peripheral blood mononuclear cells (PBMC), measured by ELISPOT assays | A response is defined as at least a 5 fold higher frequency of INF-gamma secreting CD8 T cells after vaccination than before. A patient also will be considered a responder if no specific PSA: 154-163(155L) response was found before vaccination and a specific PSA: 154-163(155L) response is identified after vaccination. | From baseline to 1 week after the last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of treatment on serum prostate-specific antigen level | The PSA reduction is defined as is at least 50% fall in the serum PSA level after vaccination. The proportion of patients who showed a reduction in serum PSA will be estimated and corresponding 95% confidence intervals will be calculated. | Up to 4 weeks after completion of study treatment | 
| Incidence of adverse events graded according to NCI CTCAE version 3.0 |  | Up to 4 weeks after completion of study treatment |