To Evaluate Sipuleucel-T Manufactured With Different Concentrations of (PA2024) Antigen

• ClinicalTrials.gov Identifier: NCT00715078
• Recruitment Status: Completed
• First Posted: July 15, 2008
• Results First Posted: May 12, 2014
• Last Update Posted: May 23, 2017
• Sponsor: Dendreon
• Information provided by (Responsible Party): Dendreon

Tracking Information

• First Submitted Date: July 11, 2008
• First Posted Date: July 15, 2008
• Results First Submitted Date: February 19, 2014
• Results First Posted Date: May 12, 2014
• Last Update Posted Date: May 23, 2017
• Study Start Date: October 2008
• Actual Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2017)

Cumulative CD54 Upregulation Ratio Between Each of the Cohorts. [ Time Frame: Baseline, Months 2, 4 and 6. ]

An analysis of variance model for the log transformed cumulative CD54 upregulation ratio (CD54 upregulation is the fold increase in the final product (FP) from buoyant density separations (BDS) step 65. BDS65 step refers to sample taken after both BDS77 and BDS65 but before ex vivo culture in the presence of antigen PA2024. FP refers to sample taken after ex vivo culture) that includes the antigen concentration cohort as the independent variable was performed. Subjects who received all 3 infusions were included.

• Original Primary Outcome Measures (submitted: July 14, 2008): Compare the cumulative CD54 upregulation ratio between each of the cohorts. [ Time Frame: 2010 ]
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: July 14, 2008)

• Evaluate the magnitude of the immune response in each of the cohorts. [ Time Frame: Overall survival will be evaluated after the last living subject has completed the Month 36 visit. ]
• Evaluate the overall survival in each of the cohorts. [ Time Frame: Overall survival will be evaluated after the last living subject has completed the Month 36 visit. ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: To Evaluate Sipuleucel-T Manufactured With Different Concentrations of (PA2024) Antigen
• Official Title: A Randomized, Multicenter, Single Blind Study in Men With Metastatic Androgen Independent Prostate Cancer to Evaluate Sipuleucel-T Manufactured With Different Concentrations of PA2024 Antigen
• Brief Summary: This is a randomized, multicenter, single blind, Phase 2 trial of immunotherapy in men with metastatic androgen independent prostate cancer to evaluate sipuleucel-T manufactured with different concentrations of PA2024 antigen
• Detailed Description: This is a randomized, multicenter, single blind, Phase 2 trial of immunotherapy in men with metastatic androgen independent prostate cancer to evaluate sipuleucel-T manufactured with 1 of 3 different concentrations of PA2024 antigen The primary purpose of this study is to compare the changes in CD54 upregulation between each of these 3 groups of subjects.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

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)

Study Arms

• Active Comparator: Cohort A
  Sipuleucel-T with the concentration of 10 μg/mL PA2024 in a cell suspension of 1 x 10^7 peripheral blood mononuclear cells (PBMCs) per mL. Subjects received infusion of sipuleucel-T, at 2-week intervals, for a total of 3 infusions.
  Intervention: Biological: sipuleucel-T
• Active Comparator: Cohort B
  Sipuleucel-T with the concentration of 5 μg/mL PA2024 in a cell suspension of 1 x 10^7 PBMCs per mL. Subjects received infusion of sipuleucel-T, at 2-week intervals, for a total of 3 infusions.
  Intervention: Biological: sipuleucel-T
• Active Comparator: Cohort C
  Sipuleucel-T with the concentration of 2 μg/mL PA2024 in a cell suspension of 1 x 10^7 PBMCs per mL. Subjects received infusion of sipuleucel-T, at 2-week intervals, for a total of 3 infusions.
  Intervention: Biological: sipuleucel-T

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 30, 2013): 122
• Original Estimated Enrollment (submitted: July 14, 2008): 120
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

For a subject to be eligible for participation in this study, all of the following criteria must be satisfied.

• Histologically documented adenocarcinoma of the prostate.
• Metastatic disease.
• Progressive androgen independent castrate resistant prostate cancer.
• Serum PSA ≥ 5.0 ng/mL.
• Life expectancy of ≥ 6 months.
• Castrate level of testosterone (< 50 ng/dL) achieved via medical or surgical castration.
• Men ≥ 18 years of age.
• Adequate hematologic, renal and liver function.

Exclusion Criteria:

A subject will not be eligible for participation in this study if any of the following criteria apply.

• The presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites.
• A requirement for treatment with opioid analgesics for any reason within 21 days prior to registration.
• Moderate to severe disease related pain.
• Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.
• Use of non-steroidal antiandrogens within 6 weeks of registration.
• Anti-androgen withdrawal response.
• Treatment with chemotherapy within 3 months of registration.
• More than 2 chemotherapy regimens prior to registration.
• Initiation or discontinuation of bisphosphonate therapy within 28 days prior to registration.

• Treatment with any of the following medications or interventions within 28 days of registration:

  • Systemic corticosteroids,
  • External beam radiation therapy or surgery,
  • Dietary and herbal supplements, as well as alternative treatments that have evidence of hormonal and/or anticancer properties (e.g., prostate cancer (PC) -SPES or PC-SPEC) and saw palmetto,
  • Megestrol acetate (Megace®), diethylstilbesterol (DES), or cyproterone acetate, ++Ketoconazole,
  • 5-alpha-reductase inhibitors,
  • High dose calcitriol [1,25(OH)2Vitamin D] (i.e., > 0.5 mcg/day).
• Any other systemic therapy for prostate cancer (except for medical castration).
• Treatment with any investigational vaccine within 2 years of registration or treatment with any other investigational product within 28 days of registration.
• Participation in any previous study involving sipuleucel-T, regardless of whether the subject received sipuleucel-T (APC8015) or placebo.
• Known pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression.
• A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease-free at the time of registration. Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years at the time of registration.
• A requirement for systemic immunosuppressive therapy for any reason.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or granulocyte-macrophage colony-stimulating factor.
• Any infection requiring parenteral antibiotic therapy or causing fever (temp > 100.5°F or > 38.1°C) within 1 week prior to registration.
• Any medical intervention or other condition which, in the opinion of the Principal Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00715078
• Other Study ID Numbers: P07-2
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Dendreon
• Study Sponsor: Dendreon
• Collaborators: Not Provided

Investigators

• Study Director: Robert Israel, MD; Valeant Pharmaceuticals North America LLC

• PRS Account: Dendreon
• Verification Date: April 2017