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
- Conditions
- Prostate Cancer Metastatic
- Interventions
- Registration Number
- NCT01322490
- Lead Sponsor
- Bavarian Nordic
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1297
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).
-
Radiological progression defined as any new/enlarging bone metastases or new/enlarging lymph node disease, consistent with prostate cancer.
OR
-
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).
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PROSTVAC-V/F-TRICOM + GM-CSF PROSTVAC-V * PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF PROSTVAC-V/F-TRICOM + GM-CSF PROSTVAC-F * PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF PROSTVAC-V/F-TRICOM + GM-CSF placebo GM-CSF Placebo * PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF placebo Placebo Control GM-CSF Placebo PROSTVAC V/F Placebo + GM-CSF Placebo Placebo Control Placebo PROSTVAC V/F Placebo + GM-CSF Placebo PROSTVAC-V/F-TRICOM + GM-CSF placebo PROSTVAC-V * PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF placebo PROSTVAC-V/F-TRICOM + GM-CSF placebo PROSTVAC-F * PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF placebo PROSTVAC-V/F-TRICOM + GM-CSF GM-CSF * PROSTVAC-V-TRICOM * PROSTVAC-F-TRICOM * GM-CSF
- Primary Outcome Measures
Name Time Method Overall Survival 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. The time between the date of randomization and the date of death due to any cause. Subjects who did not experience death or the competing events of "definite" loss to follow-up or withdrawal of consent were right censored at the date of last contact. OS was calculated using the formula: OS = Date of death/competing event/censoring - date of randomization + 1.
- Secondary Outcome Measures
Name Time Method Number of Subjects Alive Without Event at 6 Months Randomization through Week 25/End of Treatment visit. A binary assessment that was performed for the 6-months timepoint for the categories of radiographic progression, pain progression, initiation of chemotherapy or death. Subjects without an event prior to 6-months were evaluated at 6-months. Subjects without event by 6-months and were not evaluated at 6-months were assumed to have had an event and analyzed as such.
Progression events were defined as: (1) Two new lesions on bone scan, new metastases on CT scans, or an increased size of nodal lesions per RECIST 1.1. Bone or CT scans occurring prior to calendar month 6 were used to determine radiographic progression. (2) Introduction of scheduled opioid narcotics for cancer-related pain control. (3) Initiation of chemotherapy for prostate cancer was assessed as collected on progression forms as well as in cancer treatment and concomitant medications logs. (4) Death.
Trial Locations
- Locations (219)
Alaska Clinical Research Center, Llc
🇺🇸Anchorage, Alaska, United States
Scottsdale Healthcare
🇺🇸Scottsdale, Arizona, United States
Alta Bates Summit Medical Center
🇺🇸Berkeley, California, United States
Prostate Oncology Specialists, Inc.
🇺🇸Marina Del Rey, California, United States
Desert Hematology-Oncology
🇺🇸Rancho Mirage, California, United States
San Bernardino Urological Associates
🇺🇸San Bernardino, California, United States
Stanford Advanced Medical Center
🇺🇸Stanford, California, United States
South Florida Medical Research
🇺🇸Aventura, Florida, United States
Manatee Medical Research Institute, LLC
🇺🇸Bradenton, Florida, United States
Florida Urology Physicians
🇺🇸Fort Myers, Florida, United States
First Urology PSC
🇺🇸Jeffersonville, Indiana, United States
Pinellas Urology, Inc.
🇺🇸Saint Petersburg, Florida, United States
Palm Beach Cancer Institute
🇺🇸West Palm Beach, Florida, United States
Lakeland Regional Cancer Center
🇺🇸Lakeland, Florida, United States
North Idaho Urology
🇺🇸Coeur d'Alene, Idaho, United States
Northern Indiana Cancer Research Consortium
🇺🇸South Bend, Indiana, United States
The Iowa Clinic, PC Iowa Urology
🇺🇸West Des Moines, Iowa, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
Myron Murdock M.D. LLC
🇺🇸Greenbelt, Maryland, United States
Kansas City VA Medical Center
🇺🇸Kansas City, Missouri, United States
University Urology Associates
🇺🇸New York, New York, United States
The Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Brooklyn Urology Research Group
🇺🇸Brooklyn, New York, United States
Presbyterian Hospital Center for Cancer Research
🇺🇸Charlotte, North Carolina, United States
Hudson Valley Urology, P.C.
🇺🇸Poughkeepsie, New York, United States
Northeast Urology Research
🇺🇸Concord, North Carolina, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
W.G. (Bill) Hefner VA Medical Center
🇺🇸Salisbury, North Carolina, United States
Urologic Consultants of Southeaster PA LLP
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Willamette Valley Cancer Center
🇺🇸Springfield, Oregon, United States
Urological Associates Of Lancaster
🇺🇸Lancaster, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Greenville Hospital System
🇺🇸Greenville, South Carolina, United States
Ralph H Johnson VAMC
🇺🇸Charleston, South Carolina, United States
WJB Dorn VA Medical Center
🇺🇸Columbia, South Carolina, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
University of TN Medical Center
🇺🇸Knoxville, Tennessee, United States
The West Clinic, P.C.
🇺🇸Memphis, Tennessee, United States
James H. Quillen Veterans Affairs Medical Center
🇺🇸Mountain Home, Tennessee, United States
Central Texas Veterans Health Care System
🇺🇸Temple, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
White River Junction Veterans Affairs Medical Center
🇺🇸White River Junction, Vermont, United States
Virginia Oncology Associates PC
🇺🇸Norfolk, Virginia, United States
Washington Cancer Institute
🇺🇸Washington, District of Columbia, United States
Ochsner Cancer Institute
🇺🇸New Orleans, Louisiana, United States
Delaware Valley Urology LLC - Westhampton
🇺🇸Mount Laurel, New Jersey, United States
VA Sierra Nevada HealthCare System
🇺🇸Reno, Nevada, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
The Schiffler Cancer Center
🇺🇸Wheeling, West Virginia, United States
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Redcliffe Hospital
🇦🇺Redcliffe, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Monash Medical Centre - Moorabbin Campus
🇦🇺Bentleigh East, Australia
St John of God Hospital
🇦🇺Subiaco, Australia
Barwon Health
🇦🇺Geelong, Australia
Border Medical Oncology
🇦🇺Wodonga, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Ziekenhuisnetwerk Antwerpen - AZ Middelheim
🇧🇪Antwerp, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
AZ Maria Middelares
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
H.-Hartziekenhuis Roeselare-Menen vzw
🇧🇪Roeselare, Belgium
Brantford Urology Research
🇨🇦Brantford, Ontario, Canada
Capital District Health Authority
🇨🇦Halifax, Nova Scotia, Canada
Southern Interior Medical Research Inc.
🇨🇦Kelowna, British Columbia, Canada
Cambridge Memorial Hospital
🇨🇦Cambridge, Ontario, Canada
St. Josephs Healthcare Hamilton Research Ethics Board
🇨🇦Hamilton, Ontario, Canada
The Female/Male Health Centres
🇨🇦Oakville, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Centre Hospitalier Universitaire de Quebec Hotel Dieu
🇨🇦Quebec, Canada
Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
North Estonia Medical Centre Foundation
🇪🇪Tallinn, Estonia
Centre Hospitalier Départemental La Roche sur Yon, Luçon, Montaigu - Les Oudaries
🇫🇷La Roche Sur Yon, France
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
Centre Paul Papin
🇫🇷Angers, France
Centre d'Oncologie de Gentilly
🇫🇷Nancy, France
Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes
🇫🇷Lyon, France
HIA du Val de Grâce
🇫🇷Paris, France
Fondation Hôpital Saint-Joseph
🇫🇷Paris, France
Institut Curie
🇫🇷Paris, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
Institut Jean Godinot - Centre de lutte contre le cancer
🇫🇷Reims, France
Clinique Armoricaine de Radiologie
🇫🇷Saint Brieuc, France
Hôpital Bretonneau
🇫🇷Tours, France
Centre Alexis Vautrin - Centre Régional de lutte contre le cancer de Lorraine
🇫🇷Vandoeuvre les Nancy, France
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Stadtisches Klinikum Muchen GmbH
🇩🇪Munich, Bavaria, Germany
Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main
🇩🇪Frankfurt, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Martini-Klinik am UKE GmbH
🇩🇪Hamburg, Germany
Klinikum der Friedrich-Schiller-Universität Jena
🇩🇪Jena, Germany
Chirurgische Universitätsklinik Freiburg
🇩🇪Freiburg, Germany
Universitatsklinikum Ulm
🇩🇪Ulm, Germany
Klinikum der Philipps-Universität Marburg
🇩🇪Marburg, Germany
Universitätsmedizin der JGU Mainz
🇩🇪Mainz, Germany
Studienpraxis Urologie
🇩🇪Reutlingen, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Landspitali University Hospital
🇮🇸Reykjavik, Iceland
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Soroka University Medical Center
🇮🇱Beer Sheva, Israel
Bnei Zion Medical Center
🇮🇱Haifa, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Edith Wolfson Medical Center
🇮🇱Holon, Israel
Hadassah University Hospital Ein Kerem
🇮🇱Jerusalem, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Assaf Harofe Medical Center
🇮🇱Tzrifin, Israel
NKI-AVL
🇳🇱Amsterdam, Netherlands
VUMC
🇳🇱Amsterdam, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Urologica Praktyka Lekarska Adam Marcheluk
🇵🇱Siedlce, Poland
AMEDS CENTRUM Sp. z o.o.
🇵🇱Grodzisk Mazowiecki, Poland
Miedzyleski Szpital Specjalistyczny w Warszawie
🇵🇱Warsaw, Poland
Szpital sw Elzbiety - Mokotowskie Centrum Medyczne Sp. z o. o.
🇵🇱Warsaw, Poland
Alliance for Research and Knowledge
🇵🇷San Juan, Puerto Rico
Chelyabinsk Regional Clinical Oncology Dispensary
🇷🇺Chelyabinsk, Russian Federation
Klinika Urologii i Onkologii Urologicznej, Uniwersytecki Szpital Kliniczny we Wrocławiu
🇵🇱Wroclaw, Poland
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Russian Federation
Ponce School of Medicine
🇵🇷Ponce, Puerto Rico
Orel Oncology Center
🇷🇺Orel, Russian Federation
Moscow Research Oncology Institute n.a. P.A.Gertsen
🇷🇺Moscow, Russian Federation
St. Petersburg Medical Academy of Postgraduate Education
🇷🇺St. Petersburg, Russian Federation
Kazan State Medical University
🇷🇺Kazan, Russian Federation
Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
Orenburg Regional Clinical Oncology Center
🇷🇺Orenburg, Russian Federation
St. Petersburg State Medical University n.a. I.P. Pavlov
🇷🇺St. Petersburg, Russian Federation
"Orkli" LLC
🇷🇺St. Petersburg, Russian Federation
City Hospital #15
🇷🇺St. Petersburg, Russian Federation
"Clinic Andros" LLC
🇷🇺St.Petersburg, Russian Federation
Regional Clinical Oncology Hospital
🇷🇺Yaroslavl, Russian Federation
Regional Clinical Oncology Center
🇷🇺Vladimir, Russian Federation
Stavropol Regional Clinical Oncology Dispensary
🇷🇺Stavropol, Russian Federation
Hospital 12 de Octubre
🇪🇸Madrid, Madrid, Communidad De, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, Galicia, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Nuestra Señora de Sonsoles
🇪🇸Avila, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall D´Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Spain
MD Anderson International Espana
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Centro Integral Oncológico Clara Campal
🇪🇸Madrid, Spain
Althaia: Xarxa Assistencial de Manresa
🇪🇸Manresa, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Spain
Hospital General Carlos Haya
🇪🇸Málaga, Spain
Hospital Son Espases
🇪🇸Palma de Mallorca, Spain
Fundación Hospital Manacor
🇪🇸Palma de Mallorca, Spain
Corporació Sanitaria Parc Taulí
🇪🇸Sabadell, Spain
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Mutua de Terrassa
🇪🇸Terrassa, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Bristol Haematology & Oncology Centre
🇬🇧Bristol, UK, United Kingdom
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Velindre Hospital
🇬🇧Cardiff, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Leeds Teaching Hospitals NHS Trust, St James's University Hospital
🇬🇧Leeds, United Kingdom
St Bartholomews Hospital
🇬🇧London, United Kingdom
St Mary's Hospital
🇬🇧London, United Kingdom
Christie Hospital
🇬🇧Manchester, United Kingdom
Plymouth Hospitals NHS Trust, Derriford Hospital
🇬🇧Plymouth, United Kingdom
University of Southampton
🇬🇧Southampton, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
San Diego Clinical Trials
🇺🇸San Diego, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
VA San Diego Healthcare System
🇺🇸San Diego, California, United States
Jesse Brown VA
🇺🇸Chicago, Illinois, United States
Maryland Prostate Center
🇺🇸Baltimore, Maryland, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Union Memorial Hospital
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Regional Cancer Care PA
🇺🇸Durham, North Carolina, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Columbus Urology Research
🇺🇸Columbus, Ohio, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Cancer Pavillion
🇺🇸Pittsburgh, Pennsylvania, United States
Urology Clinics of North Texas
🇺🇸Dallas, Texas, United States
Mary Crowley Cancer Research Center
🇺🇸Dallas, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
St. Alexius Medical Center
🇺🇸Bismarck, North Dakota, United States
Aalborg Sygehus
🇩🇰Aalborg, Denmark
Frederiksberg Hospital
🇩🇰Frederiksberg, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Herlev Hospital
🇩🇰Herlev, Denmark
Holstebro Sygehus
🇩🇰Holstebro, Denmark
Storstrømmens Sygehus Næstved
🇩🇰Næstved, Denmark
Skejby Sygehus
🇩🇰Århus N, Denmark
The Urology Center of Colorado
🇺🇸Denver, Colorado, United States
Urology Associates, PC
🇺🇸Nashville, Tennessee, United States
Salt Lake Research
🇺🇸Salt Lake City, Utah, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Queen's University at Kingston
🇨🇦Kingston, Ontario, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
University of Colorado
🇺🇸Aurora, Colorado, United States
James A Haley Veteran Affairs Medical Center
🇺🇸Tampa, Florida, United States
Walter Reed Army Medical Center
🇺🇸Bethesda, Maryland, United States
National Cancer Institute - Center for Cancer Research
🇺🇸Bethesda, Maryland, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
GU Research Network, LLC
🇺🇸Omaha, Nebraska, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Hospital Universitario Fundación Alcorcón
🇪🇸Madrid, Spain
The Royal Marsden
🇬🇧London, United Kingdom
Sydney Haematology and Oncology Clinic
🇦🇺St Leonards, New South Wales, Australia
University of Surrey
🇬🇧Guildford, United Kingdom