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

Adenocarcinoma of the Prostate Clinical Trial

— ProVent  

Official title:

A Randomized Phase 3, Open-Label Trial of Sipuleucel-T Administered To Patients On Active Surveillance For Newly Diagnosed Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03686683
• Other study ID #: P17-1
• Secondary ID: ProVent
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 18, 2018
• Est. completion date: February 28, 2024

Study information

• Verified date: October 2023
• Source: Dendreon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: February 28, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 subject information redacted must be submitted for 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. Subject 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. 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

• 9. 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.

• 10. 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.

• 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 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).

• 13. Hypogonadal (T <175 ng/dL) or on continuous testosterone replacement therapy

• 14. Positive serology for HIV-1, HIV-2 or 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate

Intervention

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).

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Dendreon	PRA Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the efficacy of sipuleucel-T in reducing histopathologic reclassification to a higher Gleason grade in prostate cancer subjects on active surveillance (AS)	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.	Once all subjects have completed at least 3 years following randomization