Open- Label Trial of Sipuleucel-T Administered to Active Surveillance Patients for Newly Diagnosed Prostate Cancer (ProVent)

A Randomized Phase 3, Open-Label Trial of Sipuleucel-T Administered To Patients On Active Surveillance For Newly Diagnosed Prostate Cancer

The ProVent study is a randomized, open-label study designed to assess the efficacy of sipuleucel-T in reducing the progression of lower risk non-metastatic prostate cancer compared to subjects followed on active surveillance as standard of care.

Study Overview

• Status: Active, not recruiting
• Conditions: Adenocarcinoma of the Prostate
• Intervention / Treatment: Biological: sipuleucel-T

Detailed Description

The ProVent Study is designed to look at subjects who recieve sipuleucel-T compared to control subjects followed on AS. The study will enroll subjects being followed by AS and initially diagnosed within 12 months prior to Screening with either ISUP Grade Group 1 or 2 adenocarcinoma of the prostate.

The Screening Phase will begin at the completion of the informed consent process and continues until randomization. After Screening assessments are completed, eligible subjects will be randomized 2:1 to the sipuleucel-T arm or the control arm. Subjects randomized to sipuleucel-T arm will receive product as described in the sipuleucel-T approved label.

Subjects will undergotheir first leukapheresis within 60 days of randomization.

Subjects randomized to the control arm will be followed on AS. The Active Phase will begin at randomization and continues through completion of the end of Active Phase study visit (within 30 days of Biopsy 2). Once a subject from either the sipuleucel-T or control arms completes the end of Active Phase visit, they will enter the Follow-up Phase and complete Follow-up Phase visits every 6 months starting from their last Active Phase visit. The Follow-up Phase visits end when the last subject enrolled completes Biopsy 2 and end of Active Phase visit or until the study is terminated by the sponsor.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85741
      • Arizona Institute of Urology
    • Tucson, Arizona, United States, 85741
      • Urological Associates of Southern Arizona - East Office
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Urological Associates, PA
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Orange, California, United States, 92868
      • University of California Irvine
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
    • Torrance, California, United States, 90505
      • Skyline Urology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital Anschutz Cancer Pavilion
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
    • Golden, Colorado, United States, 80401
      • Foothills Urology- Golden Office
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Advanced Urology Institute
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Advanced Urology Institute of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Chicago, Illinois, United States, 60612
      • Cook County Health
    • Chicago, Illinois, United States, 60643
      • Research By Design
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem
    • Glenview, Illinois, United States, 60026
      • Gottlieb Memorial Hospital
    • Joliet, Illinois, United States, 60431
      • Advanced Urology Associates
    • Lake Barrington, Illinois, United States, 60010
      • Comprehensive Urologic Care
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • First Urology
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Clinical Research Corp.
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas City Urology Care, PA
    • Wichita, Kansas, United States, 67226
      • Wichita Urology Group Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • A. Alfred Taubman Health Care Center
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology, PC
  • Mississippi
    • Southaven, Mississippi, United States, 38671
      • The Urology Group
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center and GU Research Network
    • Omaha, Nebraska, United States, 68114
      • Adult Pediatric Urology and Urogynecology - Omaha
  • New Jersey
    • Mount Laurel, New Jersey, United States, 08054
      • Delaware Valley Urology
  • New York
    • Melville, New York, United States, 11747
      • Integrated Medical Professionals, PLLC
    • New York, New York, United States, 10029
      • Mount Sinai Health System
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of NY, PLLC (AMP)
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Associated Urologists of North Carolina - Raleigh
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • The Urology Group - Norwood Campus
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Oregon Urology Institute Research
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants of Southeastern Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster Urology
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Conrad Pearson Clinic
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Urology
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age is ≥ 18 years
• 2. Written informed consent provided prior to the initiation of study procedures
• 3. Histologically proven adenocarcinoma of the prostate initially diagnosed ≤12 months of Screening. All biopsy slides with subject information redacted must be submitted for BICR.
• 4. Prostate cancer diagnosis determined by BICR as one of the following: 4a. ISUP Grade Group 1 with 3 or more cores positive from a systematic (≥10 cores) biopsy 4b. ISUP Grade Group 1 with ≥ 1 core positive with ≥50% cancer involvement from a systematic (≥10 cores) biopsy 4c. ISUP Grade Group 1 from 3 or more positive cores from any combination of cores from a systematic (≥10 cores) biopsy and MRI targeted biopsy (note: multiple cores from each MRI targeted lesion will count as 1 core) 4d. ISUP Grade Group 1 from a negative systematic (≥10 cores) biopsy and an MRI targeted core positive with ≥50% cancer involvement 4e. ISUP Grade Group 2 from a systematic (≥10 cores) biopsy with <50% of the total number of any cores positive for cancer 4f. ISUP Grade Group 2 from a negative systematic (≥10 cores) biopsy and MRI targeted core(s) positive for Gleason 3+4 (see note below) 4g. ISUP Grade Group 2 from any combination of cores from a systematic (≥10 cores) biopsy and MRI targeted biopsy (see note below)

Note for 4f and 4g: the total number of positive cores must be <50% of total cores from both the systematic biopsy and MRI targeted lesions; each MRI targeted lesion, irrespective of multiple positive cores, will each count as 1 core for the total number of positive cores, e.g., 4 targeted lesions with 2 positive cores each will only add 4 to the total core count.

• 5. Subject consents to standard of care for biopsy frequency of 2 on-study prostate biopsies and to provide biopsy tissue for study endpoint analysis.
• 6. Estimated life expectancy ≥ 10 years
• 7. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate cancer progression occurs
• 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 9. Adequate baseline hematologic, renal, and liver function tests as evidenced by laboratory test results within the following ranges ≤30 days prior to randomization White blood cell (WBC) count ≥ 3.0 x 10^6 cells/mL Absolute neutrophil count (ANC) ≥ 1.5 x 10^6 cells/mL Platelet count ≥ 1.0 x10^5 cells/uL Hemoglobin (Hgb) ≥ 10.0 g/dL Creatinine ≤ 1.5 mg/dL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤ 2.0 x ULN Aspartate aminotransferase (AST) ≤ 2.0 x ULN

Exclusion Criteria:

• 1. Former therapy for prostate cancer (local or systemic)
• 2. Any previous prostatic surgical procedure that significantly changes the anatomy of prostate (at the discretion of sponsor's Medical Monitor)
• 3. Any investigational product received for prostate cancer
• 4. Prostate biopsy specimen reveals neuroendocrine or small cell features
• 5. Primary Gleason score is ≥ 4 or any Gleason pattern 5
• 6. Any evidence of locally advanced, regional or metastatic disease, including regional and distant lymph node enlargement (Nodes ≥1.5 cm in the short axis are considered pathologic and measurable)
• 7. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA)
• 8. Subject has used a 5-alpha-reductase inhibitor (e.g., finasteride or dutasteride) continuously for ≥ 6 months and within 6 months prior to study Screening
• 9. Subject has a history of any other stage I-IV malignancy, except for basal or squamous cell skin cancer. The subject must be disease free and off any malignancy-related treatment for at least 5 years.
• 10. Subject has prior use within 30 days of study Screening of any herbal, dietary, or alternative anti-cancer treatment or product, such as PC-SPES (or PC-x product), saw palmetto, ketoconazole, an estrogen-containing nutraceutical, or high dose calcitriol (>0.5 μg/day). The Investigator will consider herbal therapies on a case-by-case basis to determine whether they fall into the category of prohibited medications based on their potential for hormonal or anti-cancer or anti-cancer properties.
• 11. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis factor alpha monoclonal antibodies, glucocorticoids)
• 12. Uncontrolled, concurrent illness including, but not limited to the following: ongoing or active infection (bacterial, viral, or fungal), symptomatic congestive heart failure (New York Classification III-IV) or unstable angina pectoris within the last 6 months, or psychiatric illness that would limit compliance with study requirements as well as any condition that would preclude a subject from undergoing leukapheresis (e.g., within the previous 6 months: myocardial infarction, interventional cardiology procedure such as angioplasty or stent placement, pulmonary embolism or deep vein thrombosis).
• 13. Hypogonadal (T <175 ng/dL) or on continuous testosterone replacement therapy
• 14. Positive serology for HIV-1, HIV-2 or HTLV-1, HTLV-2
• 15. Active hepatitis B or C
• 16. Any medical intervention, any other condition, or any other circumstance which, in the opinion of the investigator or the sponsor's Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group: Sipuleucel-T; Sipuleucel-T is an autologous cellular immunotherapy available as a suspension for intravenous infusion. Subjects randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals.	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).
No Intervention: Control Arm: Active Surveillance; Subjects randomized to the control arm will be followed on Active Surveillance described in the schedule of events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the efficacy of sipuleucel-T in reducing histopathologic reclassification to a higher Gleason grade in prostate cancer subjects on active surveillance (AS)	Proportion of subjects without histological reclassification (Gleason group upgrade) within 36 months of randomization as determined by Blinded Independent Central Review (BICR) o Upgrade is defined as subjects at randomization with either International Society of Urological Pathology (ISUP) Grade Group 1 (Gleason 3+3) upgraded to Grade Group 2 (Gleason 3+4) or higher or subjects at randomization with Grade Group 2 upgraded to Grade Group 3 (Gleason 4+3) or higher.	Once all subjects have completed at least 3 years following randomization

Collaborators and Investigators

• Sponsor: Dendreon
• Collaborators: PRA Health Sciences
• Investigators: Study Director: Nadeem Sheikh, PhD, Dendreon Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): February 28, 2024

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 27, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: ISUP Grade Group 1 or 2; Number biopsies 1 or >1 (≤12 months of Screening)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: P17-1; ProVent (Other Identifier: Dendreon Pharmaceuticals LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No