PROvenge Treatment and Early Cancer Treatment
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Control; Sipuleucel-T
Intervention description: Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen.; Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 176.0
Sex: Male
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: cancer; prostate cancer; prostatectomy; PSA; sipuleucel-T; PROVENGE; APC8015; non-metastatic; nonmetastatic; androgen-sensitive; androgen sensitive; biochemical recurrence; biochemically recurrent; immune therapy; immunotherapy; vaccine; dendritic cells; antigen-presenting cells; antigen presenting cells; cancer vaccine; therapeutic vaccine; therapeutic cancer vaccine; biologic; booster

Summary:

      The PROTECT-PROvenge Treatment and Early Cancer Treatment trial was a Phase III trial for
      patients with hormone sensitive prostate cancer. The study was conducted at over 15
      participating centers throughout the US. The purpose of the study was to determine if
      sipuleucel-T was effective for treatment of early stage, non-metastatic prostate cancer. The
      study compared the active vaccine to control to determine whether the product delayed the
      time until cancer progression.
    

Eligibility criteria:

        Inclusion Criteria for the Run-In Phase (Week -13)

          -  Histologic diagnosis of adenocarcinoma of the prostate.

          -  Within at least 3 months, but not more than 10 years, prior to initiation of the
             run-in phase with LHRH-a depot, the subject has undergone a radical prostatectomy for
             Stage T1b - T3c, N0 - N1, Nx, or M0 disease Subjects who experienced their first PSA
             recurrence within 2 years post completion of initial therapy of curative intent was
             eligible without consideration of the Gleason score of the tumor specimen. Subjects
             who experienced their first PSA relapse between 2 and 10 years post completion of
             initial therapy of curative intent was eligible only if the Gleason score of the tumor
             specimen was ≥ 7.

          -  Therapeutic PSA response to primary therapy was below 0.4 ng/mL.

          -  Tumor specimen positive for PAP.

          -  PSA relapse while not currently receiving androgen ablation therapy.

          -  If androgen ablation was given for a previous PSA relapse, PSA must have increased to
             a level at least 25% above the nadir observed while on this therapy, and to an
             absolute level of at least 3 ng/mL.

          -  Subjects who had been treated with adjuvant or salvage radiation following radical
             prostatectomy, or with either LHRH-a (e.g., leuprolide acetate or goserelin acetate)
             or non-steroidal anti-androgen therapy (e.g., bicalutamide 150 mg/day) for a prior PSA
             relapse, may enter the study provided: Post-prostatectomy PSA was never ≥ 20 ng/mL;
             PSA was not rising while subject received hormonal therapy, and; For any hormonal
             therapy received, the last effective day of androgen deprivation was at least 6 months
             prior to the date of LHRH-a depot placement.

          -  Confirmed Stage M0 disease.

          -  Estimated life expectancy of at least 1 year.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          -  Ability to understand the trial procedures and requirements.

          -  ≥ 18 and ≤ 80 years of age.

          -  Ability to understand and willingness to sign an informed consent form.

        Exclusion Criteria:

        Exclusion Criteria for Entry into the Run-In Phase (Week -13)

          -  Metastasis.

          -  Clinical evidence of local recurrence other than PSA elevation (e.g., palpable
             induration or mass in the prostatic fossa).

          -  Any surgery within 4 weeks prior to the date of LHRH-a depot placement.

          -  Prior orchiectomy.

          -  PSA ≥ 20 ng/mL at any time after radical prostatectomy.

          -  Current systemic steroid therapy (inhaled or topical steroids are acceptable).

          -  Any chemotherapy within 4 months prior to the LHRH-a depot placement.

          -  Prior immunotherapy or therapy with other experimental agents for prostate cancer.

          -  Treatment with radioactive seeds within 12 months prior to the LHRH a depot placement.

          -  History of any other prior malignancy other than resected basal or squamous cell
             carcinoma of the skin within 5 years of entry.

          -  Concurrent participation in another clinical trial involving experimental medication.

          -  Any disease, condition, social, or geographical constraint that in the opinion of the
             Investigator or medical monitor reduced the probability that the subject will complete
             the trial or affects the evaluation of study end points

        Exclusion Criteria for Randomization (Week 0):

          -  Central laboratory value of PSA ≥ 1 ng/mL at the end of the LHRH-a run-in phase.

          -  Randomized more than 3 weeks following the last effective date of testicular androgen
             suppression (as described in the package insert).

          -  Any use of herbal preparations (e.g., Prostate Cancer (PC) -SPES or saw palmetto)
             within 4 weeks prior to randomization.

          -  Any contraindication to leukapheresis or infusion of sipuleucel-T or control.

          -  Positive serology for human immunodeficiency virus (HIV)-1 or 2, human lymphotropic
             virus (HTLV)-1 or 2, or evidence of active Hepatitis B or C infection.

          -  Any ongoing active bacterial, viral, or fungal infection.

        Exclusion Criteria During the Trial:

          -  The use of any systemic therapy for prostate cancer following randomization and prior
             to BF (PSA ≥ 3 ng/mL).

          -  Placement of radioactive seeds or salvage radiation before BF (PSA ≥ 3 ng/mL)
             documented.

          -  Initiation of systemic corticosteroids at doses greater than the equivalent of 40 mg
             hydrocortisone per day (inhaled steroids are allowed) before BF.