MedPath

PROvenge Treatment and Early Cancer Treatment

Phase 3
Completed
Conditions
Prostate Cancer
Interventions
Biological: Sipuleucel-T
Other: Control
Registration Number
NCT00779402
Lead Sponsor
Dendreon
Brief 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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
176
Inclusion Criteria

Not provided

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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sipuleucel-TSipuleucel-TSubjects received infusion of Sipuleucel-T, at 2-week intervals, for a total of 3 infusions.
ControlControlSubjects received infusion of control (autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen) at 2-week intervals, for a total of 3 infusions.
Primary Outcome Measures
NameTimeMethod
Time to Biochemical Failure Cumulative Incidence PercentileEvery 3 months post-infusion

Time to Biochemical Failure (TTBF) was the pre-specified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL

Number of Subjects That Met Biochemical Failure StatusEvery 3 months post-infusion

time to biochemical Failure (TTBF) was the pre-scpecified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (18)

Alta Bates Comprehensive Cancer Center

🇺🇸

Berkeley, California, United States

Urology of Virginia, PC

🇺🇸

Virginia Beach, Virginia, United States

Bryn Mawr Urology Group

🇺🇸

Rosemont, Pennsylvania, United States

Oregon Urology Institute

🇺🇸

Springfield, Oregon, United States

Mount Sinai School of Medicine

🇺🇸

New York, New York, United States

McKay Urology

🇺🇸

Charlotte, North Carolina, United States

Urology Health Specialists - Bryn Mawr

🇺🇸

Bryn Mawr, Pennsylvania, United States

Albert Einstein Medical Building

🇺🇸

Philadelphia, Pennsylvania, United States

University of Tennessee

🇺🇸

Memphis, Tennessee, United States

University of Colorado Health Sciences Center

🇺🇸

Aurora, Colorado, United States

Providence Medical Center

🇺🇸

Portland, Oregon, United States

AKSM Clinical Research Group

🇺🇸

Columbus, Ohio, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

South Orange County Medical Research

🇺🇸

Laguna Hills, California, United States

Oncology Specialists, SC

🇺🇸

Park Ridge, Illinois, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Oregon Health and Sciences University

🇺🇸

Portland, Oregon, United States

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