Vaccine Therapy in Treating Patients With Recurrent Prostate Cancer

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.

• PSA:154-163(155L) peptide vaccine (Biological), also known as PSA PEP VAC, PSA-3A: Given subcutaneously
• incomplete Freund's adjuvant (Biological), also known as IFA, ISA-51, Montanide ISA 51: Given subcutaneously
• laboratory biomarker analysis (Other): Correlative studies

Primary outcomes

• Change in frequency of CD8 T-lymphocyte precursors in peripheral blood mononuclear cells (PBMC), measured by ELISPOT assays [From baseline to 1 week after the last dose of study treatment]: 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.

Secondary outcomes

• Effect of treatment on serum prostate-specific antigen level [Up to 4 weeks after completion of study treatment]: 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.
• Incidence of adverse events graded according to NCI CTCAE version 3.0 [Up to 4 weeks after completion of study treatment]

Sex: Male, ages: 18 Years to any

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

• Results publication: Kouiavskaia DV, Berard CA, Datena E, Hussain A, Dawson N, Klyushnenkova EN, Alexander RB. Vaccination with agonist peptide PSA: 154-163 (155L) derived from prostate specific antigen induced CD8 T-cell response to the native peptide PSA: 154-163 but failed to induce the reactivity against tumor targets expressing PSA: a phase 2 study in patients with recurrent prostate cancer. J Immunother. 2009 Jul-Aug;32(6):655-66. doi: 10.1097/CJI.0b013e3181a80e0d. PMID 19483644

• H. Richard Alexander, Principal investigator, University of Maryland Greenebaum Cancer Center