Clinical trial NCT01322490: A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
Official title: A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer Metastatic
Keywords: PROSTVAC
metastatic
prostate cancer
castrate-resistant
vaccine
immunotherapy
Phase 3
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2011-03-24
Enrollment: 1297
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival in men with few or no symptoms from metastatic, castrate-resistant prostate cancer.

Detailed description: BNIT-PRV-301 is a randomized, placebo-controlled, multi-center, global Phase 3 efficacy trial of PROSTVAC in men with asymptomatic or minimally symptomatic, metastatic, castrate-resistant prostate cancer. It is a 3-arm study and will evaluate overall survival in two separate comparisons, PROSTVAC plus adjuvant dose GM-CSF versus controls, and PROSTVAC without GM-CSF versus controls.

Patients will be randomized with equal probability into one of three double-blind arms. The intended interventions for randomized patients are:

1. (Arm V+G) PROSTVAC-V/F plus adjuvant dose GM-CSF
2. (Arm V) PROSTVAC-V/F plus GM-CSF placebo
3. (Arm P) Double placebo

Eligibility criteria: Inclusion Criteria:

Men, ≥18years of age with documented asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer.

Documented progressive disease post surgical castration or during androgen suppression therapy, or during complete androgen blockade therapy and withdrawal. Documented by either criterion a (Radiological progression), OR criterion b (PSA progression).

1. Radiological progression defined as any new/enlarging bone metastases or new/enlarging lymph node disease, consistent with prostate cancer.

   OR
2. PSA progression defined by sequence of rising values separated by \> 1 week (2 separate increasing values) over a threshold minimum of 2.0 ng/ml. (PCWG2 PSA eligibility criteria).

Chemotherapy naïve and Vaccinia-experienced (previous smallpox vaccination). Currently using a GnRH agonist or antagonist (unless surgically castrated).

Exclusion Criteria:

Cancer-related pain requiring scheduled opioid narcotics for control (as needed, ≤ 2x per week is allowed).

Metastasis to organ systems other than lymph nodes and/or bone. Estimated PSA doubling time of \<1 month as established within 6 months of the anticipated first dose of vaccine or placebo.

Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer. Receipt of an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the first planned dose of PROSTVAC-V/F.

History of prior malignancies other than prostate cancer within the past 3 years, excluding successfully resected basal or squamous cell carcinoma of the skin.

Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or myocardial infarction (current or within the past 6 months) Confirmed positive for HIV, hepatitis B, and /or hepatitis C. Immunodeficiency or splenectomy. History of or active autoimmune disease, persons with vitiligo are not excluded. Diabetics are not excluded if the condition is well controlled.

History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis.

Primary outcomes:
measure: Overall Survival
timeFrame: Randomization through the date of death due to any cause. Subjects were followed up for approximately 6 years from the first subject randomized to the completion of the study.
Secondary outcomes:
measure: Number of Subjects Alive Without Event at 6 Months
timeFrame: Randomization through Week 25/End of Treatment visit.
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, Llc
state: Alaska
city: Scottsdale
country: United States
facility: Scottsdale Healthcare
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Marina Del Rey
country: United States
facility: Prostate Oncology Specialists, Inc.
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology-Oncology
state: California
city: San Bernardino
country: United States
facility: San Bernardino Urological Associates
state: California
city: San Diego
country: United States
facility: San Diego Clinical Trials
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: Stanford
country: United States
facility: Stanford Advanced Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Bradenton
country: United States
facility: Manatee Medical Research Institute, LLC
state: Florida
city: Fort Myers
country: United States
facility: Florida Urology Physicians
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Saint Petersburg
country: United States
facility: Pinellas Urology, Inc.
state: Florida
city: Tampa
country: United States
facility: James A Haley Veteran Affairs Medical Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Chicago
country: United States
facility: Jesse Brown VA
state: Illinois
city: Jeffersonville
country: United States
facility: First Urology PSC
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: West Des Moines
country: United States
facility: The Iowa Clinic, PC Iowa Urology
state: Iowa
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Baltimore
country: United States
facility: Maryland Prostate Center
state: Maryland
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Union Memorial Hospital
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed Army Medical Center
state: Maryland
city: Bethesda
country: United States
facility: National Cancer Institute - Center for Cancer Research
state: Maryland
city: Greenbelt
country: United States
facility: Myron Murdock M.D. LLC
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City VA Medical Center
state: Missouri
city: Omaha
country: United States
facility: GU Research Network, LLC
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Reno
country: United States
facility: VA Sierra Nevada HealthCare System
state: Nevada
city: Mount Laurel
country: United States
facility: Delaware Valley Urology LLC - Westhampton
state: New Jersey
city: New Brunswick
country: United States
facility: The Cancer Institute of New Jersey
state: New Jersey
city: Brooklyn
country: United States
facility: Brooklyn Urology Research Group
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Poughkeepsie
country: United States
facility: Hudson Valley Urology, P.C.
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital Center for Cancer Research
state: North Carolina
city: Concord
country: United States
facility: Northeast Urology Research
state: North Carolina
city: Durham
country: United States
facility: Regional Cancer Care PA
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Salisbury
country: United States
facility: W.G. (Bill) Hefner VA Medical Center
state: North Carolina
city: Bismarck
country: United States
facility: St. Alexius Medical Center
state: North Dakota
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Columbus Urology Research
state: Ohio
city: Springfield
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of Southeaster PA LLP
state: Pennsylvania
city: Lancaster
country: United States
facility: Urological Associates Of Lancaster
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Pavillion
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H Johnson VAMC
state: South Carolina
city: Columbia
country: United States
facility: WJB Dorn VA Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Knoxville
country: United States
facility: University of TN Medical Center
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic, P.C.
state: Tennessee
city: Mountain Home
country: United States
facility: James H. Quillen Veterans Affairs Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Dallas
country: United States
facility: Urology Clinics of North Texas
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Temple
country: United States
facility: Central Texas Veterans Health Care System
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake Research
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: White River Junction
country: United States
facility: White River Junction Veterans Affairs Medical Center
state: Vermont
city: Norfolk
country: United States
facility: Virginia Oncology Associates PC
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Wheeling
country: United States
facility: The Schiffler Cancer Center
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: St Leonards
country: Australia
facility: Sydney Haematology and Oncology Clinic
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Redcliffe
country: Australia
facility: Redcliffe Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Bentleigh East
country: Australia
facility: Monash Medical Centre - Moorabbin Campus
city: Geelong
country: Australia
facility: Barwon Health
city: Subiaco
country: Australia
facility: St John of God Hospital
city: Wodonga
country: Australia
facility: Border Medical Oncology
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Antwerp
country: Belgium
facility: Ziekenhuisnetwerk Antwerpen - AZ Middelheim
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: H.-Hartziekenhuis Roeselare-Menen vzw
city: Kelowna
country: Canada
facility: Southern Interior Medical Research Inc.
state: British Columbia
city: Halifax
country: Canada
facility: Capital District Health Authority
state: Nova Scotia
city: Brantford
country: Canada
facility: Brantford Urology Research
state: Ontario
city: Cambridge
country: Canada
facility: Cambridge Memorial Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Josephs Healthcare Hamilton Research Ethics Board
state: Ontario
city: Kingston
country: Canada
facility: Queen's University at Kingston
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oakville
country: Canada
facility: The Female/Male Health Centres
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec Hotel Dieu
city: Aalborg
country: Denmark
facility: Aalborg Sygehus
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Frederiksberg
country: Denmark
facility: Frederiksberg Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Holstebro
country: Denmark
facility: Holstebro Sygehus
city: Næstved
country: Denmark
facility: Storstrømmens Sygehus Næstved
city: Århus N
country: Denmark
facility: Skejby Sygehus
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Angers
country: France
facility: Centre Paul Papin
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Départemental La Roche sur Yon, Luçon, Montaigu - Les Oudaries
city: Lyon
country: France
facility: Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Paris
country: France
facility: HIA du Val de Grâce
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Fondation Hôpital Saint-Joseph
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: Institut Jean Godinot - Centre de lutte contre le cancer
city: Saint Brieuc
country: France
facility: Clinique Armoricaine de Radiologie
city: Tours
country: France
facility: Hôpital Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: Centre Alexis Vautrin - Centre Régional de lutte contre le cancer de Lorraine
city: Munich
country: Germany
facility: Stadtisches Klinikum Muchen GmbH
state: Bavaria
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main
city: Freiburg
country: Germany
facility: Chirurgische Universitätsklinik Freiburg
city: Hamburg
country: Germany
facility: Martini-Klinik am UKE GmbH
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller-Universität Jena
city: Mainz
country: Germany
facility: Universitätsmedizin der JGU Mainz
city: Marburg
country: Germany
facility: Klinikum der Philipps-Universität Marburg
city: Reutlingen
country: Germany
facility: Studienpraxis Urologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Reykjavik
country: Iceland
facility: Landspitali University Hospital
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Bnei Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tzrifin
country: Israel
facility: Assaf Harofe Medical Center
city: Amsterdam
country: Netherlands
facility: NKI-AVL
city: Amsterdam
country: Netherlands
facility: VUMC
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Grodzisk Mazowiecki
country: Poland
facility: AMEDS CENTRUM Sp. z o.o.
city: Siedlce
country: Poland
facility: Urologica Praktyka Lekarska Adam Marcheluk
city: Warsaw
country: Poland
facility: Szpital sw Elzbiety - Mokotowskie Centrum Medyczne Sp. z o. o.
city: Warsaw
country: Poland
facility: Miedzyleski Szpital Specjalistyczny w Warszawie
city: Wroclaw
country: Poland
facility: Klinika Urologii i Onkologii Urologicznej, Uniwersytecki Szpital Kliniczny we Wrocławiu
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine
city: San Juan
country: Puerto Rico
facility: Alliance for Research and Knowledge
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Dispensary
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology Dispensary
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Moscow
country: Russian Federation
facility: Moscow Research Oncology Institute n.a. P.A.Gertsen
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Orel
country: Russian Federation
facility: Orel Oncology Center
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncology Center
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Medical Academy of Postgraduate Education
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Medical University n.a. I.P. Pavlov
city: St. Petersburg
country: Russian Federation
facility: City Hospital #15
city: St. Petersburg
country: Russian Federation
facility: "Orkli" LLC
city: St.Petersburg
country: Russian Federation
facility: "Clinic Andros" LLC
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Clinical Oncology Dispensary
city: Vladimir
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
state: Galicia
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
state: Madrid, Communidad De
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Avila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall D´Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: MD Anderson International Espana
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Alcorcón
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Manresa
country: Spain
facility: Althaia: Xarxa Assistencial de Manresa
city: Málaga
country: Spain
facility: Hospital General Carlos Haya
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Palma de Mallorca
country: Spain
facility: Fundación Hospital Manacor
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
state: UK
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Guildford
country: United Kingdom
facility: University of Surrey
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust, St James's University Hospital
city: London
country: United Kingdom
facility: St Bartholomews Hospital
city: London
country: United Kingdom
facility: The Royal Marsden
city: London
country: United Kingdom
facility: St Mary's Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust, Derriford Hospital
city: Southampton
country: United Kingdom
facility: University of Southampton
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
affiliation: National Cancer Institute (NCI)
name: James L. Gulley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute
name: Philip Kantoff, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, Pook DW, Rathenborg P, Flaig TW, Carles J, Saad F, Shore ND, Chen L, Heery CR, Gerritsen WR, Priou F, Langkilde NC, Novikov A, Kantoff PW. Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2019 May 1;37(13):1051-1061. doi: 10.1200/JCO.18.02031. Epub 2019 Feb 28.