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

• Sponsor: Dendreon (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03686683
• Collaborator: PRA Health Sciences (Industry)
• Enrollment: 450
• Locations: 56
• Arms: 2
• Anticipated Duration (Months): 54.4
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 subjects followed on active surveillance as standard of care.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate	Biological: sipuleucel-T	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized 2:1 to the sipuleucel-T arm or the control arm.Subjects randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals. Subjects randomized to the control arm will be followed on AS as standard of care described in the schedule of events.Subjects will be randomized 2:1 to the sipuleucel-T arm or the control arm.Subjects randomized to sipuleucel-T arm will receive 3 infusions of sipuleucel-T at approximately 2-week intervals. Subjects randomized to the control arm will be followed on AS as standard of care described in the schedule of events.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 3, Open-Label Trial of Sipuleucel-T Administered To Patients On Active Surveillance For Newly Diagnosed Prostate Cancer
• Actual Study Start Date: Oct 18, 2018
• Anticipated Primary Completion Date: May 1, 2023
• Anticipated Study Completion Date: May 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. To assess the efficacy of sipuleucel-T in reducing histopathologic reclassification to a higher Gleason grade in prostate cancer subjects on active surveillance (AS) [Once all subjects have completed at least 3 years following randomization]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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 subject information redacted must be submitted for 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. Subject 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. 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
• 1. 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.
• 1. 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.
• 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 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).
• 1. Hypogonadal (T <175 ng/dL) or on continuous testosterone replacement therapy
• 1. Positive serology for HIV-1, HIV-2 or 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	Arizona Institute of Urology	Tucson	Arizona	United States	85741
3	Urological Associates of Southern Arizona - East Office	Tucson	Arizona	United States	85741
4	Arkansas Urological Associates, PA	Little Rock	Arkansas	United States	72211
5	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92093
6	VA Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
7	University of California Irvine	Orange	California	United States	92868
8	John Wayne Cancer Institute	Santa Monica	California	United States	90404
9	Skyline Urology	Torrance	California	United States	90505
10	University of Colorado Hospital Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
11	The Urology Center of Colorado	Denver	Colorado	United States	80211
12	Foothills Urology- Golden Office	Golden	Colorado	United States	80401
13	Advanced Urology Institute	Daytona Beach	Florida	United States	32114
14	Advanced Urology Institute of Georgia	Roswell	Georgia	United States	30076
15	Cook County Health	Chicago	Illinois	United States	60612
16	Rush University	Chicago	Illinois	United States	60612
17	Research by Design	Chicago	Illinois	United States	60643
18	Gottlieb Memorial Hospital	Glenview	Illinois	United States	60026
19	NorthShore University HealthSystem	Glenview	Illinois	United States	60026
20	Advanced Urology Associates	Joliet	Illinois	United States	60431
21	Comprehensive Urologic Care	Lake Barrington	Illinois	United States	60010
22	First Urology	Jeffersonville	Indiana	United States	47130
23	Iowa Clinical Research Corp.	West Des Moines	Iowa	United States	50266
24	Kansas City Urology Care, PA	Overland Park	Kansas	United States	66211
25	Wichita Urology Group Research	Wichita	Kansas	United States	67226
26	Tulane University	New Orleans	Louisiana	United States	70112
27	Regional Urology, LLC	Shreveport	Louisiana	United States	71106
28	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21224
29	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889
30	Chesapeake Urology	Towson	Maryland	United States	21204
31	A. Alfred Taubman Health Care Center	Ann Arbor	Michigan	United States	48109
32	Michigan Institute of Urology, PC	Troy	Michigan	United States	48084
33	The Urology Group	Southaven	Mississippi	United States	38671
34	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
35	Adult Pediatric Urology and Urogynecology - Omaha	Omaha	Nebraska	United States	68114
36	Urology Cancer Center and GU Research Network	Omaha	Nebraska	United States	68130
37	Delaware Valley Urology	Mount Laurel	New Jersey	United States	08054
38	Integrated Medical Professionals, PLLC	Melville	New York	United States	11747
39	Mount Sinai Health System	New York	New York	United States	10029
40	Associated Medical Professionals of NY, PLLC (AMP)	Syracuse	New York	United States	13210
41	Associated Urologists of North Carolina - Raleigh	Raleigh	North Carolina	United States	27612
42	The Urology Group - Norwood Campus	Cincinnati	Ohio	United States	45212
43	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
44	Oregon Urology Institute Research	Springfield	Oregon	United States	97477
45	Urologic Consultants of Southeastern Pennsylvania	Bala-Cynwyd	Pennsylvania	United States	19004
46	Lancaster Urology	Lancaster	Pennsylvania	United States	17604
47	Omega Medical Research	Warwick	Rhode Island	United States	02886
48	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
49	The Conrad Pearson Clinic	Germantown	Tennessee	United States	38138
50	Urology Associates	Nashville	Tennessee	United States	37209
51	Vanderbilt University	Nashville	Tennessee	United States	37232
52	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
53	Urology San Antonio	San Antonio	Texas	United States	78229
54	Virginia Urology	Richmond	Virginia	United States	23235
55	Urology of Virginia	Virginia Beach	Virginia	United States	23462
56	Virginia Mason Medical Center	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Dendreon
• PRA Health Sciences

Investigators

• Study Director: Nadeem Sheikh, PhD, Dendreon Pharmaceuticals LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dendreon
• ClinicalTrials.gov Identifier: NCT03686683
• Other Study ID Numbers: P17-1; ProVent
• First Posted: Sep 27, 2018
• Last Update Posted: Jan 20, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dendreon: ISUP Grade Group 1 or 2; Number biopsies 1 or >1 (≤12 months of Screening)
• Additional relevant MeSH terms: Adenocarcinoma

Study Results

No Results Posted as of Jan 20, 2022