Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer
Condition: Cancer of Prostate; Cancer of the Prostate; Neoplasms, Prostate; Neoplasms, Prostatic; Prostate Cancer; Prostate Neoplasms; Prostatic Cancer
MeSH terms: Prostatic Neoplasms; Neoplasms
Intervention: androgen ablation (AA); DC1 vaccine
Intervention description: Lupron 22.5 mg or Zoladex 10.8 mg; 3-5 x 10e6 cells total
Intervention MeSH terms: Vaccines; Androgens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Vaccine; Androgen Ablation; PSA Progression

Summary:

      This study will evaluate the feasibility, safety, and efficacy of intradermal vaccination of
      prostate cancer patients with alpha-type-1-polarized dendritic cells (DC1) loaded with
      apoptotic allogeneic tumor (LNCap). The study will target men with recurrent prostate cancer,
      who failed local therapy, have no measurable metastasis, but have a rising PSA with a
      doubling time of less than 10 months. The selection of this study group enables us to
      evaluate time to PSA progression, a highly relevant, clinical primary endpoint of efficacy in
      this two arm study. In order to facilitate infiltration of vaccination-induced T cells into
      tumor site(s) and to reduce tumor-specific tolerance, subjects will receive the vaccine in
      combination with limited androgen ablation (AA) with a LHRH analogue for 3 months. Subjects
      will be randomly assigned to one of two cohorts. In cohort A subjects will be first treated
      with limited AA alone for 3 months, and at the time of PSA relapse (PSA ≥ 1 ng/dL) will
      receive the DC vaccine in conjunction with AA. In cohort B, the sequence of treatment will be
      reversed. Efficacy will be estimated as the within-subject difference in time to PSA relapse
      following the combination treatment as compared to the AA alone, thus, each subject will
      serve as his own control. All subjects will commence the DC1-based vaccination 2 weeks prior
      to treatment with the LHRH analogue. Each subject will receive 1 intradermal (i.d.) dose of
      the vaccine at weeks 1, 5, 9, and 13 for a total of 4 doses. Additional courses of
      vaccination may be administered to subjects without evidence of disease progression every 3
      months (±1 month) for up to 12 months depending on the number of doses originally produced
      and available after the 4 intended protocol doses. All doses of the vaccine will be
      administered intradermally (i.d.).
    

Eligibility criteria:

        Eligibility Criteria

          -  Patients with histologically proven prostate cancer and tumors limited to the prostate
             (including seminal vesicle involvement, provided all visible disease was surgically
             removed) who have completed local therapy and have an elevated PSA after surgery or
             rising PSA after radiation therapy, as defined below.

          -  Age 18 years or older

          -  Histologically confirmed diagnosis of prostate cancer.

          -  Previous treatment with definitive surgery or radiation therapy or both.

          -  No evidence of metastatic disease on physical exam, CT/MRI/CXR (see Section 7.1 for
             radiologic imaging), and bone scan within 4 weeks prior to randomization.

          -  Prior neoadjuvant/adjuvant hormonal, androgen deprivation therapy, or chemotherapy is
             allowed if it was last used > 12 months prior to first vaccination.

          -  No therapy modulating testosterone levels (such as leuteinizing-hormone
             releasing-hormone agonists/antagonists and antiandrogens) is permitted within 12
             months prior to first vaccination. Agents such as 5α-reductase inhibitors,
             ketoconazole, megestrol acetate, systemic steroids (replacement doses of steroids are
             allowed), PC-SPES, and Saw Palmetto are not permitted at any time during the period
             that the PSA values are being collected.

          -  Hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150
             ng/dL or > 6 nmol/L at the time of enrollment within 4 weeks prior to randomization.

          -  All patients must have evidence of biochemical progression as determined by a
             reference PSA value followed by 1 confirmatory rising PSA value, higher than the
             previous value, obtained at least 2 weeks apart. All of these PSA values must be
             obtained at the same reference lab, and all must be done within 6 months prior to
             enrollment.

          -  The most recent of the PSA values must be ≥ 2.0 ng/mL. This measurement must be
             obtained within 1 month prior to enrollment.

          -  The PSA doubling time (PSA-DT) must be less than 12 months.

          -  ECOG performance status 0 or 1.

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count > 1,500/µL

               -  Platelets > 100,000/µL

               -  Total bilirubin 1.5 x upper limit of normal (ULN)

               -  SGOT (AST) and SGPT (ALT) < 2.5 x institutional ULN

               -  Creatinine 1.5 x ULN

          -  The effects of dendritic cell vaccines on the developing human fetus are unknown. For
             this reason men must agree to use adequate contraception (hormonal or barrier method
             of birth control) prior to study entry and for the duration of study participation.

        Exclusion Criteria

          -  Patients must not be receiving other investigational agents or concurrent anticancer
             therapy.

          -  No 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.

          -  Patients must not have active eczema, atopic dermatitis, or other exfoliative skin
             conditions (e.g., burns, impetigo, varicella zoster, severe acne, contact dermatitis,
             psoriasis, herpes or other open rashes or wounds).

          -  Presence of an active acute or chronic infection, including urinary tract infection,
             HIV or viral hepatitis. HIV patients are excluded based on immunosuppression which may
             render them unable to respond to the vaccine; patients with chronic hepatitis are
             excluded because of concern that hepatitis could be exacerbated by the injections. If
             clinically indicate, HIV/viral hepatitis testing will be performed to confirm status.

          -  Patients with a history of auto-immune disease such as, but not restricted to,
             inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,
             scleroderma, or multiple sclerosis. Patients receiving replacement thyroid hormone
             would be eligible.

          -  No concurrent use of systemic steroids, except for local (topical, nasal, or inhaled)
             steroid use. Adrenal replacement doses of corticosteroids are allowed.

          -  Subjects with concurrent additional malignancy (with exception of non-melanoma skin
             cancers and superficial bladder cancer or malignancy within last 3 years).