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

Phase 3

Completed

Conditions: Adenocarcinoma of the Prostate

Interventions: Biological: sipuleucel-T

Registration Number: NCT03686683

Lead Sponsor: Dendreon

Brief Summary: 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 participants followed on active surveillance as standard of care.

Detailed Description: The ProVent Study is designed to look at participants who receive sipuleucel-T compared to control participants followed on active surveillance (AS). The study will enroll participants being followed by AS and initially diagnosed within 12 months prior to Screening with either International Society of Urological Pathology (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 participants will be randomized 2:1 to the sipuleucel-T arm or the control arm. Participants randomized to sipuleucel-T arm will receive product as described in the sipuleucel-T approved label.

Participants will undergo their first leukapheresis within 60 days of randomization.

Participants 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 Participant 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 Participant enrolled completes Biopsy 2 and end of Active Phase visit or until the study is terminated by the sponsor.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 532

Inclusion Criteria

1. Age is ≥ 18 years
1. Written informed consent provided prior to the initiation of study procedures
1. Histologically proven adenocarcinoma of the prostate initially diagnosed ≤12 months of Screening. All biopsy slides with participant information redacted must be submitted for blinded independent central review (BICR).
1. 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.

1. Participant consents to standard of care for biopsy frequency of 2 on-study prostate biopsies and to provide biopsy tissue for study endpoint analysis.
1. Estimated life expectancy ≥ 10 years
1. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate cancer progression occurs
1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
1. 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)
1. Any previous prostatic surgical procedure that significantly changes the anatomy of prostate (at the discretion of sponsor's Medical Monitor)
1. Any investigational product received for prostate cancer
1. Prostate biopsy specimen reveals neuroendocrine or small cell features
1. Primary Gleason score is ≥ 4 or any Gleason pattern 5
1. 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)
1. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA)
1. Participant has used a 5-alpha-reductase inhibitor (e.g., finasteride or dutasteride) continuously for ≥ 6 months and within 6 months prior to study Screening
1. Participant has a history of any other stage I-IV malignancy, except for basal or squamous cell skin cancer. The Participant must be disease free and off any malignancy-related treatment for at least 5 years.
1. Participant 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.
1. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis factor alpha monoclonal antibodies, glucocorticoids)
1. 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 participant 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).
1. Hypogonadal (T <175 ng/dL) or on continuous testosterone replacement therapy
1. Positive serology for HIV-1, HIV-2 or human T-lymphotropic virus (HTLV)-1, HTLV-2
1. Active hepatitis B or C
1. 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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group: Sipuleucel-T	sipuleucel-T	Sipuleucel-T is an autologous cellular immunotherapy available as a suspension for intravenous infusion. Participants randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals.

Primary Outcome Measures

Name	Time	Method
Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade).	Once all participants have completed at least 3 years following randomization	Percentage of participants without histological reclassification (Gleason group upgrade) within 36 months of randomization as determined by Blinded Independent Central Review (BICR) o Upgrade is defined as participants 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 participants at randomization with Grade Group 2 upgraded to Grade Group 3 (Gleason 4+3) or higher.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (56): Johns Hopkins University School of Medicine
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Baltimore, Maryland, United States
VA Greater Los Angeles Healthcare System
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Los Angeles, California, United States
University of California Irvine
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Orange, California, United States
NorthShore University HealthSystem
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Glenview, Illinois, United States
Comprehensive Urologic Care
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Lake Barrington, Illinois, United States
Gottlieb Memorial Hospital
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Glenview, Illinois, United States
University of California San Diego Moores Cancer Center
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La Jolla, California, United States
John Wayne Cancer Institute
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Santa Monica, California, United States
Cook County Health
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Chicago, Illinois, United States
Mary Crowley Cancer Research
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Dallas, Texas, United States
Advanced Urology Institute
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Daytona Beach, Florida, United States
Iowa Clinical Research Corp.
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West Des Moines, Iowa, United States
Chesapeake Urology
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Towson, Maryland, United States
Oregon Urology Institute Research
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Springfield, Oregon, United States
Virginia Urology
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Richmond, Virginia, United States
Mount Sinai Health System
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New York, New York, United States
Urologic Consultants of Southeastern Pennsylvania
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Bala-Cynwyd, Pennsylvania, United States
Integrated Medical Professionals, PLLC
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Melville, New York, United States
Urology of Virginia
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Virginia Beach, Virginia, United States
Rush University
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Chicago, Illinois, United States
Skyline Urology
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Torrance, California, United States
Foothills Urology- Golden Office
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Golden, Colorado, United States
Research by Design
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Chicago, Illinois, United States
First Urology
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Jeffersonville, Indiana, United States
A. Alfred Taubman Health Care Center
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Ann Arbor, Michigan, United States
Michigan Institute of Urology, PC
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Troy, Michigan, United States
Associated Urologists of North Carolina - Raleigh
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Raleigh, North Carolina, United States
Associated Medical Professionals of NY, PLLC (AMP)
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Syracuse, New York, United States
The Urology Group - Norwood Campus
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Cincinnati, Ohio, United States
Virginia Mason Medical Center
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Seattle, Washington, United States
Wichita Urology Group Research
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Wichita, Kansas, United States
Kansas City Urology Care, PA
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Overland Park, Kansas, United States
Washington University School of Medicine
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Saint Louis, Missouri, United States
Delaware Valley Urology
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Mount Laurel, New Jersey, United States
Arizona Institute of Urology
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Tucson, Arizona, United States
Urological Associates of Southern Arizona - East Office
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Tucson, Arizona, United States
The Urology Group
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Southaven, Mississippi, United States
Arkansas Urological Associates, PA
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Little Rock, Arkansas, United States
Banner MD Anderson Cancer Center
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Gilbert, Arizona, United States
Tulane University
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New Orleans, Louisiana, United States
Regional Urology, LLC
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Shreveport, Louisiana, United States
University of Colorado Hospital Anschutz Cancer Pavilion
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Aurora, Colorado, United States
Walter Reed National Military Medical Center
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Bethesda, Maryland, United States
The Urology Center of Colorado
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Denver, Colorado, United States
Adult Pediatric Urology and Urogynecology - Omaha
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Omaha, Nebraska, United States
Urology Cancer Center and GU Research Network
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Omaha, Nebraska, United States
University of Oklahoma Health Sciences Center
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Oklahoma City, Oklahoma, United States
Urology Associates
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Nashville, Tennessee, United States
Vanderbilt University
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Nashville, Tennessee, United States
Urology San Antonio
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San Antonio, Texas, United States
Advanced Urology Associates
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Joliet, Illinois, United States
Advanced Urology Institute of Georgia
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Roswell, Georgia, United States
Lancaster Urology
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Lancaster, Pennsylvania, United States
Omega Medical Research
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Warwick, Rhode Island, United States
Carolina Urologic Research Center
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Myrtle Beach, South Carolina, United States
The Conrad Pearson Clinic
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Germantown, Tennessee, United States