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 autologous PAP-loaded dendritic cells (Provenge™) in patients with non-metastatic prostate cancer. Patients 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 efficacy endpoint is serologic (PSA) progression. The secondary endpoint is time-to progression (i.e. androgen-independent progression, distant failure, local recurrence). Data from this study will be combined with data from a similar study to provide greater statistical power to detect a difference in the secondary efficacy endpoint. An interim analysis is planned for safety parameters only.

The treatment schema is presented in Figure 1. Following short-term open-label treatment with a LH-RH (luteinizing hormone-releasing hormone)-analogue, patients are randomized to blinded treatment assignments of either the Active Vaccine or Control Vaccine Group in a 2:1 ratio. Patients undergo three leukaphereses on alternate weeks (Weeks 0, 2 and 4 post randomization). Leukapheresis material is shipped to regional cell-processing centers for generating PAP-loaded dendritic cells. Two days following leukapheresis, patients receive an infusion with either Provenge™ or control infusion.

Patients complete an elicited symptom log at specified times during the study aimed to compare androgen suppression-related side effects during periods with and without androgen suppression. Patients are evaluated periodically for safety and efficacy endpoints.

Median time from randomization to serologic progression (PSA rise to > 3 ng/mL) is reported from similar patient series in the literature as 11.6 months (range 3-24 months). At the time patients develop serologic progression they are eligible for one booster vaccination with cell product, and continue to be observed until PSA exceeds a threshold value as specified in Section 6.3.1. Once this PSA threshold value is reached, patients are retreated with androgen ablation. Bone scans are repeated every other year unless clinically indicated earlier; serum PSA and testosterone are monitored quarterly by a central lab until the patient completes the study or withdraws.

Approximately 159 patients will be accrued in 10-15 urologic/oncology care institutions in the United States. The anticipated patient accrual period is 18 months.

• Other: Placebo
• Biological: Provenge

• Experimental: Provenge
• 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.