Provenge (TM) for the Treatment of Hormone Sensitive Prostate Cancer (PROTECT)

The PROTECT-PROvenge Treatment and Early Cancer Treatment trial is a Phase IIIB trial for patients with hormone sensitive prostate cancer. The study is being conducted at over 15 participating centers throughout the US. The purpose of the study is to determine if Provenge is effective for treatment of early stage, non-metastatic prostate cancer. If you have rising PSA after radical prostatectomy, but have no evidence yet of metastasis, you may be eligible. The study compares the active vaccine to placebo (your dendritic cells that were not activated in the laboratory) to determine whether the product delays the time until the cancer progresses.

This is 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 qualifying for this study are men who have previously undergone a prostatectomy and whose only sign of disease recurrence is a rise in serum prostate specific antigen (PSA).

The primary objectives are to compare the time to biochemical failure (BF, PSA greater than or equal to 3 ng/mL) between sipuleucel-T (treatment group) and placebo (control group), and to study the safety of sipuleucel-T. The secondary objectives are to compare time to distant failure (DF, distant metastatic disease), PSA doubling time (PSADT), and survival between the 2 treatment groups.

Following short-term open-label treatment with a luteinizing hormone-releasing hormone-analogue (LHRH-a), subjects are randomized to blinded treatment assignments of either sipuleucel-T or placebo in a 2:1 ratio. Following randomization, subjects will undergo 3 leukapheresis procedures on alternate weeks (Weeks 0, 2, and 4). Approximately three days following each leukapheresis procedure, subjects will receive an infusion of either sipuleucel-T or placebo.

Subjects will complete a checklist at specified times during the study. This checklist is designed to compare androgen suppression-related side effects during periods with and without androgen suppression. Subjects will be evaluated periodically for safety and efficacy endpoints.

At the time BF is confirmed, subjects will be eligible for a booster infusion. The booster process will consist of 1 leukapheresis procedure followed by 1 infusion of the same treatment assignment, sipuleucel-T or placebo, allocated at randomization.

Subjects will continue to be observed until DF is confirmed by bone scan or computed tomography (CT) scan, or other imaging modalities as clinically indicated. After confirmed DF, subjects will be followed for safety and survival for the remainder of their lives. The total time on study for each subject is estimated to be approximately 10 to 13 years.

• Other: Placebo
  Non autologous PAP loaded dendritic cells
• Biological: Provenge
  Biologic: Immunotherapy with PAP loaded dendritic cells.
  Other Name: APC8015

• Experimental: 1
  Provenge
  Intervention: Biological: Provenge
• 2
  Placebo
  Intervention: Other: Placebo

Patients are eligible if they have:

• Histologic diagnosis of adenocarcinoma of the prostate;
• At least 3 months but no more than 8 years prior to study entry, undergone a radical prostatectomy for stage T1b – T3c, N0-N1, M0 disease, with or without subsequent adjuvant or salvage radiation therapy. Patients who experience their first PSA recurrence within 2 years post completion of initial therapy of curative intent are eligible without consideration of the Gleason score of the tumor specimen.* Patients who experience their first PSA relapse between 2 and 8 years post completion of initial therapy of curative intent are eligible only if the Gleason score of the tumor specimen was > 7; (* For patients who received adjuvant radiation, the date of the final dose of radiotherapy is used to mark the date of completion of therapy of curative intent. For patients who received salvage radiation for post-operative PSA recurrence but no adjuvant radiation, the date of surgery marks the date of completion of therapy of curative intent.)
• Therapeutic PSA response to primary therapy below 0.4 ng/mL;
• Tumor specimen positive for PAP, the vaccine’s target. Immunohistological staining of a specimen from the surgically excised tumor for expression of PAP is conducted by IMPATH, and may be completed even after LH-RH-analogue placement, as long as a positive (+) result is confirmed prior to randomization (Week 0). If a slide of the tumor cannot be obtained from the pathology archive, a chart record from a PRE-SURGERY blood sample showing serum PAP elevated above the upper limit of the local reference range may serve as a proxy.
• Experienced PSA relapse while not currently receiving androgen ablation therapy. Specifically, on record must be 2 PSA values separated by at least 3 months, both in the detectable range (>0.5 ng/mL), showing an increase of at least 0.3 ng/mL between the 2 measurements. The first of these 2 PSA values must rise above a previously recorded post-operative nadir value (which may be an undetectable PSA). In patients who received androgen ablation 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;

• Prior hormone treatment for an earlier episode of PSA relapse is neither an exclusion nor an inclusion requirement for study entry. Patients who have previously been treated with adjuvant or salvage radiation following radical prostatectomy, or with either LH-RH-analogue (i.e., leuprolide or goserelin acetate) or non-steroidal anti-androgen therapy (i.e., 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 receiving adequately dosed hormonal therapy;
  • for any hormonal therapy received, the last effective day of androgen deprivation was at least 6 months prior to study entry;
• Confirmed M0; a bone scan with no evidence of osseous metastasis must be on record, dated within 6 months prior to entry into the study;
• Estimated life-expectancy, inclusive consideration of co-morbidities, of at least 1 year;
• ECOG performance status of 0 or 1;
• Ability to understand the trial procedures and requirements;
• Age >18 and < 80 years;
• Ability to understand, and willingness to sign, informed consent.