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.

This was a prospective, double blind, controlled, randomized trial of immunotherapy with prostatic acid phosphatase (PAP)-loaded autologous antigen presenting cells (APCs), in subjects with non metastatic prostate cancer. Subjects that qualified for this study were men who had previously undergone a prostatectomy and whose only sign of disease recurrence was a rise in serum prostate specific antigen (PSA).

The primary objectives were to compare the time to biochemical failure (BF, PSA greater than or equal to 3 ng/mL) between sipuleucel-T (treatment group) and control, and to study the safety of sipuleucel-T.

Following short-term open-label treatment with a luteinizing hormone-releasing hormone-analogue (LHRH-a), Subjects completed a checklist designed to compare androgen suppression-related side effects during periods with and without androgen suppression.

Subjects who achieved a PSA of < 1 ng/ml were randomized to blinded treatment assignments of either sipuleucel-T or control in a 2:1 ratio. Following randomization, subjects underwent 3 leukapheresis procedures on alternate weeks (Weeks 0, 2, and 4). Approximately three days following each leukapheresis procedure, subjects received an infusion of either sipuleucel-T or control.

At the time BF was confirmed, subjects were eligible for a booster infusion. The booster process consisted of 1 leukapheresis procedure followed by 1 infusion of sipuleucel-T. The booster process, in effect under protocol amendment 5, differed from the previous booster process that consisted of 1 infusion of the same treatment assigned at randomization (sipuleucel-T or control).

Subjects continued to be observed until DF was confirmed by bone scan or computed tomography (CT) scan, or other imaging modalities as clinically indicated. After confirmed DF, subjects were followed by telephone every 6 months for safety and survival, treatment-related AEs, any CVEs, or new therapies for prostate cancer.

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.