PROvenge Treatment and Early Cancer Treatment

Prostate Cancer Clinical Trial

— PROTECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00779402
• Other study ID #: P-11
• Status: Completed
• Phase: Phase 3
• First received: October 22, 2008
• Last updated: June 29, 2017
• Start date: October 2001
• Est. completion date: May 2015

Study information

• Verified date: June 2017
• Source: Dendreon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: May 2015
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Other:
• Control
Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen.

Biological:
• Sipuleucel-T
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).

Locations

Country	Name	City	State
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Urology Health Specialists - Bryn Mawr	Bryn Mawr	Pennsylvania
United States	McKay Urology	Charlotte	North Carolina
United States	AKSM Clinical Research Group	Columbus	Ohio
United States	South Orange County Medical Research	Laguna Hills	California
United States	University of Tennessee	Memphis	Tennessee
United States	Mount Sinai School of Medicine	New York	New York
United States	Oncology Specialists, SC	Park Ridge	Illinois
United States	Albert Einstein Medical Building	Philadelphia	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Providence Medical Center	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	Bryn Mawr Urology Group	Rosemont	Pennsylvania
United States	Swedish Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Oregon Urology Institute	Springfield	Oregon
United States	Urology of Virginia, PC	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Dendreon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Biochemical Failure Cumulative Incidence Percentile	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	Every 3 months post-infusion
Primary	Number of Subjects That Met Biochemical Failure Status	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.	Every 3 months post-infusion

External Links

•   Prostate Cancer Research Institute
•   USTOO International