- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00779402
PROvenge Treatment and Early Cancer Treatment (PROTECT)
Autologous PAP-loaded Dendritic Cell Vaccine (Sipuleucel-T, APC8015, Provenge®) in Patients With Non-metastatic Prostate Cancer Who Experience PSA Elevation Following Radical Prostatectomy: a Randomized, Controlled, Double-blind Trial
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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California
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Berkeley, California, United States, 94704
- Alta Bates Comprehensive Cancer Center
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Laguna Hills, California, United States, 92653
- South Orange County Medical Research
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Colorado
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Aurora, Colorado, United States, 80045-3206
- University of Colorado Health Sciences Center
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Illinois
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Park Ridge, Illinois, United States, 60068-1174
- Oncology Specialists, SC
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New York
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New York, New York, United States, 10029
- Mount Sinai School of Medicine
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Rochester, New York, United States, 14642-0001
- University of Rochester Medical Center
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North Carolina
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Charlotte, North Carolina, United States, 28207
- McKay Urology
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Ohio
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Columbus, Ohio, United States, 43214
- AKSM Clinical Research Group
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Sciences University
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Portland, Oregon, United States, 97213
- Providence Medical Center
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Springfield, Oregon, United States, 97477
- Oregon Urology Institute
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Pennsylvania
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Bryn Mawr, Pennsylvania, United States, 19010
- Urology Health Specialists - Bryn Mawr
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Philadelphia, Pennsylvania, United States, 19141
- Albert Einstein Medical Building
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Rosemont, Pennsylvania, United States, 19010
- Bryn Mawr Urology Group
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Tennessee
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Memphis, Tennessee, United States, 38163
- University of Tennessee
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Virginia
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Virginia Beach, Virginia, United States, 23462
- Urology of Virginia, PC
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Washington
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Seattle, Washington, United States, 98101
- Virginia Mason Medical Center
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Seattle, Washington, United States, 98104
- Swedish Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Sipuleucel-T
Subjects received infusion of Sipuleucel-T, at 2-week intervals, for a total of 3 infusions.
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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).
Other Names:
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Placebo Comparator: Control
Subjects 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.
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Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Biochemical Failure Cumulative Incidence Percentile
Time Frame: Every 3 months post-infusion
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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
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Every 3 months post-infusion
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Number of Subjects That Met Biochemical Failure Status
Time Frame: Every 3 months post-infusion
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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.
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Every 3 months post-infusion
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- immunotherapy
- cancer
- prostate cancer
- vaccine
- PSA
- cancer vaccine
- non-metastatic
- prostatectomy
- biologic
- immune therapy
- dendritic cells
- nonmetastatic
- booster
- biochemical recurrence
- antigen-presenting cells
- antigen presenting cells
- therapeutic vaccine
- therapeutic cancer vaccine
- sipuleucel-T
- PROVENGE
- APC8015
- androgen-sensitive
- androgen sensitive
- biochemically recurrent
Additional Relevant MeSH Terms
Other Study ID Numbers
- P-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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