This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Concurrent vs. Sequential Sipuleucel-T & Abiraterone Treatment in Men With Metastatic Castrate Resistant Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dendreon
ClinicalTrials.gov Identifier:
NCT01487863
First received: December 6, 2011
Last updated: May 11, 2017
Last verified: May 2017
  Purpose
The purpose of this study was to evaluate the impact of concurrent versus sequential administration of abiraterone acetate plus prednisone on the ability to manufacture sipuleucel-T (by assessing sipuleucel-T product parameters), and to assess the safety and efficacy of sipuleucel-T with concurrent or sequential administration of abiraterone acetate plus prednisone in men with metastatic castrate resistant prostate cancer.

Condition Intervention Phase
Prostate Cancer Metastatic Hormone Refractory Prostate Cancer Castration-resistant Prostate Cancer Biological: sipuleucel-T Drug: abiraterone acetate Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Randomized, Open-label, Phase 2 Trial of Sipuleucel-T With Concurrent Versus Sequential Administration of Abiraterone Acetate Plus Prednisone in Men With Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Resource links provided by NLM:


Further study details as provided by Dendreon:

Primary Outcome Measures:
  • Cumulative CD54 Upregulation Ratio Between the Cohorts. [ Time Frame: Over the course of sipuleucel-T therapy (approximately 1 month) ]
    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.


Enrollment: 69
Study Start Date: December 2011
Study Completion Date: June 2016
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Concurrent Arm
Subjects received sipuleucel-T concurrent with abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone treatment started the next day after the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death, occurred.
Biological: sipuleucel-T
Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).
Other Names:
  • PROVENGE(R)
  • APC8015
Drug: abiraterone acetate
Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.
Other Name: ZYTIGA(R)
Experimental: Sequential Arm
Subjects received sipuleucel-T therapy followed by abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone started at week 10 from the start of the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death, occurred.
Biological: sipuleucel-T
Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).
Other Names:
  • PROVENGE(R)
  • APC8015
Drug: abiraterone acetate
Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.
Other Name: ZYTIGA(R)

Detailed Description:

Subjects underwent screening procedures at the Screening Visit to ensure that they met the inclusion and exclusion criteria outlined in the protocol. Subjects were evaluated for eligibility criteria, and if eligible, were registered and randomized in a 1:1 into either the Concurrent Arm or the Sequential Arm.

Subjects in both arms underwent a standard 1.5 to 2.0 blood volume leukapheresis, followed approximately 3 days later by an intravenous (IV) infusion of sipuleucel-T. This process occurred at approximately 2-week intervals. A course of sipuleucel-T treatment comprised three infusions.

Following the first infusion, subjects were limited to a maximum of three total product failures for all subsequent infusions, due specifically to insufficient total nucleated cell (TNC) count and/or CD54 upregulation. These subjects received no further leukaphereses or sipuleucel-T infusions, but did receive abiraterone acetate plus prednisone per the schedule of the arm to which they were randomized. All subjects received a total of 26 weeks of abiraterone acetate plus prednisone therapy.

All immune monitoring (IM) endpoints were collected from all subjects who received at least one infusion. Cellular and serological immune responses were assessed for subjects in both arms. In both arms, IM blood samples were collected at baseline (screening); pre-leukapheresis 2 and 3; post-infusion 1, 2, and 3; and weeks 6, 10, 14, and 26, with the timing of IM visits based on the onset of treatment (Day 0). Day 0 was the day of the first infusion. Post-infusion blood draws occurred at 3 hours (allowable window 1-24 hours) after each infusion. If a subject received only one or two infusions, immune samples were still drawn at the scheduled time points based on the first infusion (Day 0). If the subject was not scheduled to undergo further leukapheresis, no other pre-leukapheresis procedures were conducted.

During the active follow-up phase, subjects were followed from registration through the Post-Treatment Visit (30-37 days post-last study treatment), or until disease progression, unacceptable toxicity, or death, whichever occurred first.

During the long-term follow-up (LTFU) phase, subjects were followed from the Post-Treatment Visit for up to 3 years from the date of registration/randomization. During the LTFU phase, only new treatment-related serious adverse event (SAE)s, cerebrovascular event (CVE)s (regardless of causality), the first anti-cancer therapy and first chemotherapy, and survival status were collected via a quarterly telephone call.

Overall survival was measured as the time from randomization until death over a 3-year period.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically documented prostate cancer confirmed by a pathology report from prostate biopsy or radical prostatectomy specimen
  • metastatic status as evidenced by imaging obtained </= 56 days prior to registration demonstrating bone metastasis or lymph node metastasis
  • castrate resistant prostate cancer: castrate levels of testosterone (</= 50 ng/dL); evidence of disease progression concomitant with surgical or medical castration
  • serum PSA >/= 2.0 ng/mL
  • castrate levels of testosterone (</= 50 ng/dL) achieved via medical or surgical castration
  • baseline Eastern Cooperative Oncology Group (ECOG) performance status of </= 1
  • systolic blood pressure (BP) </= 140 mm Hg and diastolic BP </= 90 mm Hg at screening
  • adequate baseline hematologic, renal, and liver functions
  • must live in a permanent residence within a comfortable driving distance (round trip within one day) of the clinical trial site

Exclusion Criteria:

  • the presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites
  • New York Heart Association Class III or IV heart failure
  • any medical condition that may be compromised by increases in blood pressure, hypokalemia, or fluid retention
  • Child-Pugh Class B or C hepatic insufficiency
  • spinal cord compression, imminent long bone fracture, or any other condition likely to require radiation therapy and/or steroids for pain control
  • known adrenalcortical insufficiency
  • any medical contraindications to receiving prednisone
  • prior treatment with sipuleucel-T
  • previous treatment with abiraterone acetate (Zytiga(R)) or ipilimumab (Yervoy(TM))
  • a requirement for systemic immunosuppressive therapy for any reason. Use of inhaled, intra-nasal, intra-articular, and topical steroids was allowed.
  • treatment with any investigational vaccine or immunotherapy
  • treatment with any chemotherapy prior to registration.
  • 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.
  • myocardial infarction or ventricular or atrial arrhythmia within 6 months prior to registration
  • ongoing anti-androgen withdrawal response.
  • systemic steroid use within ≤ 60 days of registration
  • treatment with denosumab (Xgeva(R) or Prolia (R)) within ≤ 3 months prior to registration
  • positive test for human immunodeficiency virus (HIV) or human T cell lymphotrophic virus (HTLV) infections. Subjects with a positive test for hepatitis B or hepatitis C were allowed provided they meet the liver function test (LFT) criteria and have no signs of acute infection or active disease.
  • treatment with any of the following medications or interventions within 28 days prior to registration: external beam radiation or major surgery requiring general anesthetic; saw palmetto; megestrol acetate (Megace(R)), diethylstilbestrol, and cyproterone; 5-alpha-reductase inhibitors (e.g. finasteride [Proscar(R)], dutasteride [Avodart(R)]); steroidal anti-androgen therapy; any other systemic therapy for prostate cancer, except for medical castration; treatment with any other investigational product for prostate cancer; substrates of CYP2D6 (e.g. including but not limited to thioridazine); inhibitors of CYP3A4 (e.g. including but not limited to ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, and voriconazole); inducers of CYP3A4 (e.g. including but not limited to phenytoin, carbamazepine, rifampin, rifapentine, and phenobarbital)
  • a requirement for treatment with opioid analgesics within 21 days prior to registration
  • an active infection or infection requiring parenteral antibiotic therapy or causing fever within 7 days of registration
  • any medical intervention, or other condition, or any other circumstance that, in the opinion of the Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01487863

Locations
United States, California
UCSD Medical Center - La Jolla
La Jolla, California, United States, 92037
Moores UCSD Cancer Center
La Jolla, California, United States, 92093
Cancer Center Oncology Medical Group
La Mesa, California, United States, 91942
UCSD Medical Center - Hillcrest
San Diego, California, United States, 92103
Medical Oncology Associates - SD
San Diego, California, United States, 92123
Sharp Rees-Stealy
San Diego, California, United States, 92123
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Colorado
The Urology Center of Colorado
Denver, Colorado, United States, 80211
United States, District of Columbia
Georgetown University Medical Center - Lombardi Cancer Center
Washington, D.C., District of Columbia, United States, 20007
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
Mid Atlantic Urology Associates, Mid Atlantic Clinical Research
Greenbelt, Maryland, United States, 20770
United States, Nebraska
GU Research Center, LLC
Omaha, Nebraska, United States, 68130
United States, New York
NYU Clinical Cancer Center, NYU Langone Medical Center
New York, New York, United States, 10016
The Mount Sinai Medical Center
New York, New York, United States, 10029
Associated Medical Professionals of NY, PLLC
Oneida, New York, United States, 13421
Associated Medical Professionals of New York, PLLC
Syracuse, New York, United States, 13210
United States, Oregon
Providence Cancer Center Oncology and Hematology Care
Portland, Oregon, United States, 97213
United States, South Carolina
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States, 29572
United States, Tennessee
Urology Associates, P.C.
Nashville, Tennessee, United States, 37209
United States, Virginia
Urology of Virginia
Virginia Beach, Virginia, United States, 23462
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Dendreon
Investigators
Study Director: Robert Israel, MD Valeant Pharmaceuticals North America LLC
  More Information

Responsible Party: Dendreon
ClinicalTrials.gov Identifier: NCT01487863     History of Changes
Other Study ID Numbers: P11-3
Study First Received: December 6, 2011
Results First Received: March 27, 2017
Last Updated: May 11, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Dendreon:
prostate cancer
prostate
androgen independent prostate cancer (AIPC)
androgen-independent
androgen independent
hormone insensitive
hormone-insensitive
prostate specific antigen (PSA)
prostatic adenocarcinoma
hormone-refractory
hormone refractory
hormone refractory prostate cancer (HRPC)
immune therapy
immunotherapy
vaccine
dendritic cells
antigen-presenting cells
antigen presenting cells
cancer vaccine
therapeutic vaccine
therapeutic cancer vaccine
recombinant
biological
biopharmaceutical
biotechnology
biotech
castration resistant prostate cancer (CRPC)
castration-resistant prostate cancer (CRPC)
castration-resistance
sipuleucel-T

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Abiraterone Acetate
Androgens
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 22, 2017