Sequencing of Sipuleucel-T and ADT in Men With Non-metastatic Prostate Cancer

NCT ID: NCT01431391

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-12-31

Brief Summary

The main purpose of this study was to determine whether ADT started before or after sipuleucel-T led to a better immune system response. This study also evaluated the safety of sipuleucel-T and ADT treatment, immune system responses over time, the characteristics of sipuleucel-T, and changes in prostate specific antigen (PSA) values over time.

Detailed Description

Multicenter, randomized, open-label study, with subjects allocated (1:1) to 1 of 2 study arms, using a stratified randomization based on:

• Prostate-specific antigen doubling time (PSADT): ≤ 3 months or > 3 months and ≤ 12 months. • Primary therapy: radical prostatectomy (RP) or radiation, including brachytherapy, (XRT) or RP + XRT.

Arm 1: Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT.

Arm 2: Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions.

Cellular and humoral immune responses were assessed for Arm 2 subjects at 12, 8, and 4 weeks pre infusion 1, and in all subjects (both arms) at pre-leukapheresis 1, 2, and 3, and post-infusion 1, 2 and 3, and at the following time points after the third infusion: Weeks 2, 6, and 12 and Months 6, 9, 12, 15, 18, 21, and 24.

Safety assessments included adverse event (AE) monitoring, laboratory tests (complete blood count (CBC) and serum chemistry), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, as well PSA and testosterone monitoring. The study was complete at the 27-Month visit for Arm 1 and the 24-Month visit for Arm 2.

Conditions

Prostatic Neoplasm; Prostate Cancer; Prostatic Adenocarcinoma

Study Design

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

Study Groups

Arm 1: Sipuleucel-T followed by ADT

Arm 1: Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

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).

leuprolide acetate

Intervention Type: DRUG

45.0 mg depot injection, 2 doses 6 months apart

Arm 2: ADT followed by sipuleucel-T

Arm 2: Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

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).

leuprolide acetate

Intervention Type: DRUG

45.0 mg depot injection, 2 doses 6 months apart

Interventions

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).

Intervention Type: BIOLOGICAL

leuprolide acetate

45.0 mg depot injection, 2 doses 6 months apart

Intervention Type: DRUG

Other Intervention Names

PROVENGE®; APC8015; Eligard®

Eligibility Criteria

Inclusion Criteria

• Hormone-sensitive prostate cancer
• Non-metastatic disease, as evidenced by negative bone scan or computed tomography of the abdomen and pelvis
• ECOG performance status ≤ 1
• Histologically documented prostate cancer
• Prior primary therapy for prostate cancer
• Rising PSA with a PSADT of ≤ 12 months
• Testosterone ≥ 200 ng/dL ≤ 28 days of registration
• Adequate hematologic, renal, and liver function
• Must live in a permanent residence within a comfortable driving distance (round-trip within one day) to the clinical research site

Exclusion Criteria

• Requires systemic ongoing immunosuppressive therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF
• Prior sipuleucel-T therapy
• Prior ADT therapy ≤ 6 months prior to registration or ≥ 6 months duration in total
• If subject has a history of any other stage III/IV malignancy, the subject must be disease free and off any malignancy-related treatment for at least 10 years. If the subject has a history of any stage I-II malignancy, the subject must be disease free and off any malignancy-related treatment for at least 5 years.
• Prior experimental immunotherapy or on an experimental clinical trial within 1 year
• Received denosumab or XRT ≤ 6 months prior to registration
• Received chemotherapy or GM-CSF ≤ 90 days prior to registration
• Received any of the following medications or interventions ≤ 28 days prior to registration

• major surgery requiring general anesthesia
• systemic immunosuppressive therapy
• other prescription treatment for prostate cancer
• Active infection within 1 week of registration
• Likely to receive XRT or surgery for prostate cancer during the study period
• Any medical intervention, any other condition, or any circumstances that could compromise the study.

• 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

Urology Center of Alabama

Homewood, Alabama, United States

University of California San Diego / Moores Cancer Center

La Jolla, California, United States

Keck Hospital of USC

Los Angeles, California, United States

LAC + USC Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

NYOH Albany Cancer Center at Patroon Creek

Albany, New York, United States

Community Care Physicians, PC

Albany, New York, United States

Grand Strand Urology

Myrtle Beach, South Carolina, United States

Urology San Antonio Research

San Antonio, Texas, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Other Identifiers

P10-2

Identifier Type: -

Identifier Source: org_study_id