Clinical trial NCT03686683: Open- Label Trial of Sipuleucel-T Administered to Active Surveillance Patients for Newly Diagnosed Prostate Cancer
Official title: A Randomized Phase 3, Open-Label Trial of Sipuleucel-T Administered To Patients On Active Surveillance For Newly Diagnosed Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adenocarcinoma of the Prostate
Keywords: ISUP Grade Group 1 or 2
Number biopsies 1 or >1 (≤12 months of Screening)
Lead sponsor: Dendreon
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2018-09-27
Enrollment: 532
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Efficacy of Sipuleucel-T Measured as the Percentage of Subjects Without Histological Reclassification (Gleason Group Upgrade).
timeFrame: Once all participants have completed at least 3 years following randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Institute of Urology
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona - East Office
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urological Associates, PA
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Torrance
country: United States
facility: Skyline Urology
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Cancer Pavilion
state: Colorado
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Golden
country: United States
facility: Foothills Urology- Golden Office
state: Colorado
city: Daytona Beach
country: United States
facility: Advanced Urology Institute
state: Florida
city: Roswell
country: United States
facility: Advanced Urology Institute of Georgia
state: Georgia
city: Chicago
country: United States
facility: Cook County Health
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Chicago
country: United States
facility: Research by Design
state: Illinois
city: Glenview
country: United States
facility: Gottlieb Memorial Hospital
state: Illinois
city: Glenview
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Joliet
country: United States
facility: Advanced Urology Associates
state: Illinois
city: Lake Barrington
country: United States
facility: Comprehensive Urologic Care
state: Illinois
city: Jeffersonville
country: United States
facility: First Urology
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Clinical Research Corp.
state: Iowa
city: Overland Park
country: United States
facility: Kansas City Urology Care, PA
state: Kansas
city: Wichita
country: United States
facility: Wichita Urology Group Research
state: Kansas
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Towson
country: United States
facility: Chesapeake Urology
state: Maryland
city: Ann Arbor
country: United States
facility: A. Alfred Taubman Health Care Center
state: Michigan
city: Troy
country: United States
facility: Michigan Institute of Urology, PC
state: Michigan
city: Southaven
country: United States
facility: The Urology Group
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Adult Pediatric Urology and Urogynecology - Omaha
state: Nebraska
city: Omaha
country: United States
facility: Urology Cancer Center and GU Research Network
state: Nebraska
city: Mount Laurel
country: United States
facility: Delaware Valley Urology
state: New Jersey
city: Melville
country: United States
facility: Integrated Medical Professionals, PLLC
state: New York
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY, PLLC (AMP)
state: New York
city: Raleigh
country: United States
facility: Associated Urologists of North Carolina - Raleigh
state: North Carolina
city: Cincinnati
country: United States
facility: The Urology Group - Norwood Campus
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Springfield
country: United States
facility: Oregon Urology Institute Research
state: Oregon
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of Southeastern Pennsylvania
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster Urology
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Germantown
country: United States
facility: The Conrad Pearson Clinic
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio
state: Texas
city: Richmond
country: United States
facility: Virginia Urology
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Dendreon Pharmaceuticals, LLC
name: Nadeem Sheikh, PhD
role: STUDY_DIRECTOR
References: