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

NCT03686683 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: P17-1ProVent
• Study Type: interventional
• Target: 532
• Locations: 1 country
• Sites: 56

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.

Conditions

Adenocarcinoma of the Prostate

Keywords

ISUP Grade Group 1 or 2; Number biopsies 1 or >1 (≤12 months of Screening)

Outcome Measures

Primary Outcomes (1)

• Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade).

  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.

  Once all participants have completed at least 3 years following randomization

Study Arms (2)

Treatment Group: Sipuleucel-T

EXPERIMENTAL

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.

Biological: sipuleucel-T

Control Arm: Active Surveillance

NO INTERVENTION

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

Interventions

sipuleucel-T 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).

Treatment Group: Sipuleucel-T

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Males with proven adenocarcinoma of the prostate
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age is ≥ 18 years
• \. Written informed consent provided prior to the initiation of study procedures
• \. 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).
• \. 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.
• \. Participant consents to standard of care for biopsy frequency of 2 on-study prostate biopsies and to provide biopsy tissue for study endpoint analysis.
• \. Estimated life expectancy ≥ 10 years
• \. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate cancer progression occurs
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 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

You may not qualify if:

• \. Former therapy for prostate cancer (local or systemic)
• \. Any previous prostatic surgical procedure that significantly changes the anatomy of prostate (at the discretion of sponsor's Medical Monitor)
• \. Any investigational product received for prostate cancer
• \. Prostate biopsy specimen reveals neuroendocrine or small cell features
• \. Primary Gleason score is ≥ 4 or any Gleason pattern 5
• \. 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)
• \. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA)
• \. 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
• \. 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.
• \. 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.
• \. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis factor alpha monoclonal antibodies, glucocorticoids)
• \. 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).
• \. Hypogonadal (T \<175 ng/dL) or on continuous testosterone replacement therapy
• \. Positive serology for HIV-1, HIV-2 or human T-lymphotropic virus (HTLV)-1, HTLV-2
• \. Active hepatitis B or C

Sponsors & Collaborators

• Dendreon: lead
• PRA Health Sciences: collaborator

Study Sites (56)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Arizona Institute of Urology

Tucson, Arizona, 85741, United States

Location

Urological Associates of Southern Arizona - East Office

Tucson, Arizona, 85741, United States

Location

Arkansas Urological Associates, PA

Little Rock, Arkansas, 72211, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

VA Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

Skyline Urology

Torrance, California, 90505, United States

Location

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

The Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

Foothills Urology- Golden Office

Golden, Colorado, 80401, United States

Location

Advanced Urology Institute

Daytona Beach, Florida, 32114, United States

Location

Advanced Urology Institute of Georgia

Roswell, Georgia, 30076, United States

Location

Cook County Health

Chicago, Illinois, 60612, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Research by Design

Chicago, Illinois, 60643, United States

Location

Gottlieb Memorial Hospital

Glenview, Illinois, 60026, United States

Location

NorthShore University HealthSystem

Glenview, Illinois, 60026, United States

Location

Advanced Urology Associates

Joliet, Illinois, 60431, United States

Location

Comprehensive Urologic Care

Lake Barrington, Illinois, 60010, United States

Location

First Urology

Jeffersonville, Indiana, 47130, United States

Location

Iowa Clinical Research Corp.

West Des Moines, Iowa, 50266, United States

Location

Kansas City Urology Care, PA

Overland Park, Kansas, 66211, United States

Location

Wichita Urology Group Research

Wichita, Kansas, 67226, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Regional Urology, LLC

Shreveport, Louisiana, 71106, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Chesapeake Urology

Towson, Maryland, 21204, United States

Location

A. Alfred Taubman Health Care Center

Ann Arbor, Michigan, 48109, United States

Location

Michigan Institute of Urology, PC

Troy, Michigan, 48084, United States

Location

The Urology Group

Southaven, Mississippi, 38671, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Adult Pediatric Urology and Urogynecology - Omaha

Omaha, Nebraska, 68114, United States

Location

Urology Cancer Center and GU Research Network

Omaha, Nebraska, 68130, United States

Location

Delaware Valley Urology

Mount Laurel, New Jersey, 08054, United States

Location

Integrated Medical Professionals, PLLC

Melville, New York, 11747, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

Associated Medical Professionals of NY, PLLC (AMP)

Syracuse, New York, 13210, United States

Location

Associated Urologists of North Carolina - Raleigh

Raleigh, North Carolina, 27612, United States

Location

The Urology Group - Norwood Campus

Cincinnati, Ohio, 45212, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Urology Institute Research

Springfield, Oregon, 97477, United States

Location

Urologic Consultants of Southeastern Pennsylvania

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Lancaster Urology

Lancaster, Pennsylvania, 17604, United States

Location

Omega Medical Research

Warwick, Rhode Island, 02886, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

The Conrad Pearson Clinic

Germantown, Tennessee, 38138, United States

Location

Urology Associates

Nashville, Tennessee, 37209, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Urology San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Urology

Richmond, Virginia, 23235, United States

Location

Urology of Virginia

Virginia Beach, Virginia, 23462, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

MeSH Terms

Interventions

sipuleucel-T

Results Point of Contact

• Title: Director, Clinical Operations
• Organization: Dendreon Corporation

clinical@dendreon.com

206-455-2476

Study Officials

• Nadeem Sheikh, PhD

  Dendreon Pharmaceuticals, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 2:1 to the sipuleucel-T arm or the control arm.Participants randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals. Participants randomized to the control arm will be followed on AS as standard of care described in the schedule of events.

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 27, 2018
• Study Start: October 18, 2018
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2023
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (56)