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

NCT ID: NCT03686683

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 532 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-18
• Study Completion Date: 2023-03-10

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.

Conditions

Adenocarcinoma of the Prostate

Study Design

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

Study Groups

Treatment Group: 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.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with recombinant fusion protein composed PAP linked to GM-CSF (PA2024), a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Control Arm: Active Surveillance

Participants randomized to the control arm will be followed on Active Surveillance described in the schedule of events.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

sipuleucel-T

Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with recombinant fusion protein composed PAP linked to GM-CSF (PA2024), a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Intervention Type: BIOLOGICAL

Eligibility Criteria

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 participant information redacted must be submitted for blinded independent central review (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. Participant 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. 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
• 9. 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.
• 10. 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.
• 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 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).
• 13. Hypogonadal (T <175 ng/dL) or on continuous testosterone replacement therapy
• 14. Positive serology for HIV-1, HIV-2 or human T-lymphotropic virus (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.

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

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

Dendreon

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadeem Sheikh, PhD

Role: STUDY_DIRECTOR

Dendreon Pharmaceuticals, LLC

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Arizona Institute of Urology

Tucson, Arizona, United States

Urological Associates of Southern Arizona - East Office

Tucson, Arizona, United States

Arkansas Urological Associates, PA

Little Rock, Arkansas, United States

University of California San Diego Moores Cancer Center

La Jolla, California, United States

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

University of California Irvine

Orange, California, United States

John Wayne Cancer Institute

Santa Monica, California, United States

Skyline Urology

Torrance, California, United States

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, United States

The Urology Center of Colorado

Denver, Colorado, United States

Foothills Urology- Golden Office

Golden, Colorado, United States

Advanced Urology Institute

Daytona Beach, Florida, United States

Advanced Urology Institute of Georgia

Roswell, Georgia, United States

Cook County Health

Chicago, Illinois, United States

Rush University

Chicago, Illinois, United States

Research by Design

Chicago, Illinois, United States

Gottlieb Memorial Hospital

Glenview, Illinois, United States

NorthShore University HealthSystem

Glenview, Illinois, United States

Advanced Urology Associates

Joliet, Illinois, United States

Comprehensive Urologic Care

Lake Barrington, Illinois, United States

First Urology

Jeffersonville, Indiana, United States

Iowa Clinical Research Corp.

West Des Moines, Iowa, United States

Kansas City Urology Care, PA

Overland Park, Kansas, United States

Wichita Urology Group Research

Wichita, Kansas, United States

Tulane University

New Orleans, Louisiana, United States

Regional Urology, LLC

Shreveport, Louisiana, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Chesapeake Urology

Towson, Maryland, United States

A. Alfred Taubman Health Care Center

Ann Arbor, Michigan, United States

Michigan Institute of Urology, PC

Troy, Michigan, United States

The Urology Group

Southaven, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Adult Pediatric Urology and Urogynecology - Omaha

Omaha, Nebraska, United States

Urology Cancer Center and GU Research Network

Omaha, Nebraska, United States

Delaware Valley Urology

Mount Laurel, New Jersey, United States

Integrated Medical Professionals, PLLC

Melville, New York, United States

Mount Sinai Health System

New York, New York, United States

Associated Medical Professionals of NY, PLLC (AMP)

Syracuse, New York, United States

Associated Urologists of North Carolina - Raleigh

Raleigh, North Carolina, United States

The Urology Group - Norwood Campus

Cincinnati, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oregon Urology Institute Research

Springfield, Oregon, United States

Urologic Consultants of Southeastern Pennsylvania

Bala-Cynwyd, Pennsylvania, United States

Lancaster Urology

Lancaster, Pennsylvania, United States

Omega Medical Research

Warwick, Rhode Island, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

The Conrad Pearson Clinic

Germantown, Tennessee, United States

Urology Associates

Nashville, Tennessee, United States

Vanderbilt University

Nashville, Tennessee, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

Urology San Antonio

San Antonio, Texas, United States

Virginia Urology

Richmond, Virginia, United States

Urology of Virginia

Virginia Beach, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ProVent

Identifier Type: OTHER

Identifier Source: secondary_id

P17-1

Identifier Type: -

Identifier Source: org_study_id