PSMA and TARP Peptide Vaccine With Poly IC-LC Adjuvant in HLA-A2 (+) Patients With Elevated PSA After Initial Definitive Treatment

Detailed Objectives:

1. Estimate the frequency of immunological efficacy of the vaccine by comparison of the in vitro enzyme-linked immunosorbent spot (ELISpot) test results, for each antigen (PSMA, TARP) from peripheral blood specimens collected during the periods of time defined as "before", "during" and "after" vaccination.
2. Study the safety and toxicity of varying doses of polypeptide vaccines: PSMA27-35-PSMA687-701 (VLAGGFFLLYRHVIYAPSSHNKYA) and TARP13-35 (LQLLKQSSRRLEHTFMFLRNFSL) administered with a fixed dose of Poly IC-LC (2 mg total/treatment) as adjuvant.
3. Describe the impact of the vaccine on the pattern of PSA change in 2 subsets of patients: with castrate testosterone; with non-suppressed testosterone level/not on hormone therapy.
4. Identify if there is a basis for selection of a dose of the PSMA and the TARP polypeptide vaccines for future phase II development of this vaccination strategy, considering the dose range tested.

• Peptide Vaccine (Biological), also known as Hiltonol, poly IC-LC, PSMA peptide vaccine, TARP peptide vaccine: Peptide vaccine (PSMA and TARP peptide vaccine with Poly IC-LC adjuvant). Pilot study using three treatment arms of increasing peptide dose levels (100 mcg, 300 mcg, and 1 mg) with a fixed dose of Poly IC-LC as an adjuvant. Patients were randomly assigned to one of the 3 arms upon enrollment.
• Poly IC-LC (Drug), also known as Hiltonol, NSC-301463: Administered subcutaneously, one 2 mg/ml vial,(divided into two equal portions for each injection site).

Primary outcomes

• Occurrence of Related Adverse Events - Grade 3 or Higher [Up to 48 months]: Number of participants with related Grade 3 or higher adverse events. Establish the safety and toxicity of varying doses of polypeptide vaccines PSMA and TARP administered with a fixed dose of Poly IC-LC as an adjuvant.

Secondary outcomes

• Number of Participants With Prostatic Specific Antigen (PSA) Doubling [Up to 48 months]: Number of Participants Who Had a Doubling of the PSA or Proceeded to Another Therapy. Assess the impact of the vaccine on the pattern of PSA change in patients with castrate testosterone level and in patients with non-suppressed testosterone level not on hormone therapy.
• Number of Participants Who Did Not Have PSA Doubling [Up to 48 months]: Number of participants who did not have a PSA doubling before their last study visit, median 458 days from baseline PSA (55-613).

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* History of histologically confirmed prostate cancer.
* Competence to understand the patient information and provide written informed consent, and willingness and ability to return to H. Lee Moffitt Cancer Center for planned treatments and follow-up.
* Absence of evidence of metastatic disease by current physical exam or by current imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] pelvis, and bone scan within 60 days of first treatment).
* Patients not on hormone therapy (stratum "N") must meet all of these:

  1. At least 1 year after prostatectomy, definitive prostate radiation, or other definitive-intent local therapy.
  2. No testosterone suppression therapy for at least 6 months.
  3. PSA at least 1 ng/ml, on 2 measurements, at least 2 weeks apart.
  4. Testosterone level >100 ng/ml, at start ("noncastrate").
* Patients on hormone therapy (stratum "Y") must meet all of these:

  1. On treatment with gonadotropin-releasing hormone (GnRH) agonist (or orchiectomy) at least 6 months.
  2. testosterone level <50 ng/ml, at start.
  3. PSA at least 1 ng/ml, on 2 measurements, at least 2 weeks apart.
* Laboratory values obtained 0-14 days prior to start of therapy:

  1. White blood count (WBC) over 3,500/micro L.
  2. Platelet count over 100,000 micro L.
  3. Hemoglobin over 10.0 g/dL.
  4. Serum creatinine up to 2.0 mg/dL.
  5. Alkaline phosphatase up to 2.5 x upper limit of normal (ULN).
  6. Aspartic transaminase (AST) up to 2.5 x ULN.
* Life expectancy at least 6 months.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

Exclusion Criteria:

* Known standard therapy for the patient's disease that is potentially curative.
* A known immunodeficiency including HIV. Appropriate trials for individuals with HIV may be considered at a later date.
* History of other malignancy besides prostate cancer in the last 5 years, except non-melanoma skin cancer treated with local resection only. (The effect of study treatment on other, potentially dormant malignant diseases is not known).
* Use of oral or inhaled or parenteral corticosteroids or of other immunomodulatory drugs within the 60 days of start. \[Use of steroids after start will be considered by the principal investigator (PI) on a case-by-case basis.\]
* Use of estrogens (including herbal phytoestrogens) or ketoconazole within 30 days of start, or during the study.
* Failure to fully recover to grade 1 or better from effects of prior chemotherapy regardless of interval since last treatment.
* Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational agent in last 30 days (one month washout to start of treatment; patients could register but not start until the washout).
* Known hypersensitivity to one or more components of the study medication.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Participant flow

Outcome results

• Occurrence of Related Adverse Events - Grade 3 or Higher (Primary), Number, participants: A. Level 100 mcg Peptide Vaccine 0; B. Level 300 mcg Peptide Vaccine 0; C. Level 1 mg Peptide Vaccine 0
• Number of Participants With Prostatic Specific Antigen (PSA) Doubling (Secondary), Number, participants: A. Level 100 mcg Peptide Vaccine 8; B. Level 300 mcg Peptide Vaccine 6; C. Level 1 mg Peptide Vaccine 5
• Number of Participants Who Did Not Have PSA Doubling (Secondary), Number, participants: A. Level 100 mcg Peptide Vaccine 2; B. Level 300 mcg Peptide Vaccine 4; C. Level 1 mg Peptide Vaccine 4

Adverse events

Time frame: 2 years, 9 months

Serious adverse events by term

Other adverse events by term

• Mayer Fishman, M.D., Ph.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute