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

NCT ID: NCT01487863

Last Updated: 2019-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2016-06-30

Brief Summary

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.

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.

Conditions

Prostate Cancer Metastatic; Hormone Refractory Prostate Cancer; Castration-resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

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).

abiraterone acetate

Intervention Type: DRUG

Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.

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.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

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).

abiraterone acetate

Intervention Type: DRUG

Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.

Interventions

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).

Intervention Type: BIOLOGICAL

abiraterone acetate

Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.

Intervention Type: DRUG

Other Intervention Names

PROVENGE(R); APC8015; ZYTIGA(R)

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Dendreon

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Israel, MD

Role: STUDY_DIRECTOR

Valeant Pharmaceuticals North America LLC

Locations

UCSD Medical Center - La Jolla

La Jolla, California, United States

Moores UCSD Cancer Center

La Jolla, California, United States

Cancer Center Oncology Medical Group

La Mesa, California, United States

UCSD Medical Center - Hillcrest

San Diego, California, United States

Medical Oncology Associates - SD

San Diego, California, United States

Sharp Rees-Stealy

San Diego, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Georgetown University Medical Center - Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Indiana University

Indianapolis, Indiana, United States

Mid Atlantic Urology Associates, Mid Atlantic Clinical Research

Greenbelt, Maryland, United States

GU Research Center, LLC

Omaha, Nebraska, United States

NYU Clinical Cancer Center, NYU Langone Medical Center

New York, New York, United States

The Mount Sinai Medical Center

New York, New York, United States

Associated Medical Professionals of NY, PLLC

Oneida, New York, United States

Associated Medical Professionals of New York, PLLC

Syracuse, New York, United States

Providence Cancer Center Oncology and Hematology Care

Portland, Oregon, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Urology Associates, P.C.

Nashville, Tennessee, United States

Urology of Virginia

Virginia Beach, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Countries

United States

References

Antonarakis ES, Subudhi SK, Pieczonka CM, Karsh LI, Quinn DI, Hafron JM, Wilfehrt HM, Harmon M, Sheikh NA, Shore ND, Petrylak DP. Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials. Clin Cancer Res. 2023 Jul 5;29(13):2426-2434. doi: 10.1158/1078-0432.CCR-22-3832.

Reference Type: DERIVED

PMID: 37058234 (View on PubMed)

Other Identifiers

P11-3

Identifier Type: -

Identifier Source: org_study_id