Clinical trial NCT01431391: Sequencing of Sipuleucel-T and ADT in Men With Non-metastatic Prostate Cancer
Official title: A Randomized, Open-Label, Phase 2 Trial Examining the Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men With Non-metastatic Prostate Cancer and a Rising Serum Prostate Specific Antigen After Primary Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostatic Neoplasm
Prostate Cancer
Prostatic Adenocarcinoma
Keywords: Immune therapy
Cancer vaccine
Therapeutic vaccine
Therapeutic cancer vaccine
Vaccine
Dendritic cells
PSA
Androgen deprivation therapy
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms
Prostatic Diseases
Androgens
Hormones
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Immunology
Hormone therapy
Immunotherapy
Luteinizing hormone-releasing hormone (LHRH)
Lead sponsor: Dendreon
Sponsor class: INDUSTRY
First posted: 2011-09-09
Enrollment: 68
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024
timeFrame: PA2024 ELISPOT counts at Month 24
Secondary outcomes:
measure: Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024
timeFrame: Month 24
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Urology Center of Alabama
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego / Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC + USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: NYOH Albany Cancer Center at Patroon Creek
state: New York
city: Albany
country: United States
facility: Community Care Physicians, PC
state: New York
city: Myrtle Beach
country: United States
facility: Grand Strand Urology
state: South Carolina
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Valeant Pharmaceuticals North America LLC
name: Robert Israel, MD
role: STUDY_DIRECTOR
References: