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

Prostate Cancer Metastatic Clinical Trial

— Prospect  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01322490
• Other study ID #: BNIT-PRV-301
• Status: Completed
• Phase: Phase 3
• Start date: November 28, 2011
• Est. completion date: December 15, 2017

Study information

• Verified date: August 2019
• Source: Bavarian Nordic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1297
• Est. completion date: December 15, 2017
• Est. primary completion date: September 25, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Biological:
• PROSTVAC-V

• PROSTVAC-F

Drug:
• GM-CSF

Other:
• GM-CSF Placebo

Biological:
• Placebo
PROSTVAC V/F Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Medical Centre - Moorabbin Campus	Bentleigh East
Australia	Barwon Health	Geelong
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Redcliffe Hospital	Redcliffe	Queensland
Australia	Sydney Haematology and Oncology Clinic	St Leonards	New South Wales
Australia	St John of God Hospital	Subiaco
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Border Medical Oncology	Wodonga
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	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
Canada	Brantford Urology Research	Brantford	Ontario
Canada	Cambridge Memorial Hospital	Cambridge	Ontario
Canada	Capital District Health Authority	Halifax	Nova Scotia
Canada	St. Josephs Healthcare Hamilton Research Ethics Board	Hamilton	Ontario
Canada	Southern Interior Medical Research Inc.	Kelowna	British Columbia
Canada	Queen's University at Kingston	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	The Female/Male Health Centres	Oakville	Ontario
Canada	Centre Hospitalier Universitaire de Quebec Hotel Dieu	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Denmark	Aalborg Sygehus	Aalborg
Denmark	Skejby Sygehus	Århus N
Denmark	Rigshospitalet	Copenhagen
Denmark	Frederiksberg Hospital	Frederiksberg
Denmark	Herlev Hospital	Herlev
Denmark	Holstebro Sygehus	Holstebro
Denmark	Storstrømmens Sygehus Næstved	Næstved
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	North Estonia Medical Centre Foundation	Tallinn
Estonia	Tartu University Hospital	Tartu
France	Centre Paul Papin	Angers
France	Centre Hospitalier Départemental La Roche sur Yon, Luçon, Montaigu - Les Oudaries	La Roche Sur Yon
France	Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes	Lyon
France	Centre d'Oncologie de Gentilly	Nancy
France	Fondation Hôpital Saint-Joseph	Paris
France	HIA du Val de Grâce	Paris
France	Institut Curie	Paris
France	Institut Mutualiste Montsouris	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
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
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt am Main	Frankfurt
Germany	Chirurgische Universitätsklinik Freiburg	Freiburg
Germany	Martini-Klinik am UKE GmbH	Hamburg
Germany	Klinikum der Friedrich-Schiller-Universität Jena	Jena
Germany	Universitätsmedizin der JGU Mainz	Mainz
Germany	Klinikum der Philipps-Universität Marburg	Marburg
Germany	Stadtisches Klinikum Muchen GmbH	Munich	Bavaria
Germany	Studienpraxis Urologie	Reutlingen
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitatsklinikum Ulm	Ulm
Germany	Universitätsklinikum Ulm	Ulm
Germany	Universitätsklinikum Würzburg	Würzburg
Iceland	Landspitali University Hospital	Reykjavik
Israel	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
Netherlands	NKI-AVL	Amsterdam
Netherlands	VUMC	Amsterdam
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Radboudumc	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Poland	AMEDS CENTRUM Sp. z o.o.	Grodzisk Mazowiecki
Poland	Urologica Praktyka Lekarska Adam Marcheluk	Siedlce
Poland	Miedzyleski Szpital Specjalistyczny w Warszawie	Warsaw
Poland	Szpital sw Elzbiety - Mokotowskie Centrum Medyczne Sp. z o. o.	Warsaw
Poland	Klinika Urologii i Onkologii Urologicznej, Uniwersytecki Szpital Kliniczny we Wroclawiu	Wroclaw
Puerto Rico	Ponce School of Medicine	Ponce
Puerto Rico	Alliance for Research and Knowledge	San Juan
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	Moscow Research Oncology Institute n.a. P.A.Gertsen	Moscow
Russian Federation	Clinical Oncology Dispensary	Omsk
Russian Federation	Orel Oncology Center	Orel
Russian Federation	Orenburg Regional Clinical Oncology Center	Orenburg
Russian Federation	"Orkli" LLC	St. Petersburg
Russian Federation	City Hospital #15	St. Petersburg
Russian Federation	St. Petersburg Medical Academy of Postgraduate Education	St. Petersburg
Russian Federation	St. Petersburg State Medical University n.a. I.P. Pavlov	St. Petersburg
Russian Federation	"Clinic Andros" LLC	St.Petersburg
Russian Federation	Stavropol Regional Clinical Oncology Dispensary	Stavropol
Russian Federation	Regional Clinical Oncology Center	Vladimir
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl
Spain	Hospital Nuestra Señora de Sonsoles	Avila
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall D´Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital General Universitario de Elche	Elche
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	Hospital 12 de Octubre	Madrid	Madrid, Communidad De
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Fundación Alcorcón	Madrid
Spain	MD Anderson International Espana	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda
Spain	Hospital General Carlos Haya	Málaga
Spain	Althaia: Xarxa Assistencial de Manresa	Manresa
Spain	Fundación Hospital Manacor	Palma de Mallorca
Spain	Hospital Son Espases	Palma de Mallorca
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Corporació Sanitaria Parc Taulí	Sabadell
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago de Compostela	Galicia
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Mutua de Terrassa	Terrassa
Spain	Hospital Universitario Miguel Servet	Zaragoza
United Kingdom	University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Birmingham
United Kingdom	Bristol Haematology & Oncology Centre	Bristol	UK
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	University of Surrey	Guildford
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	The Royal Marsden	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 States	Alaska Clinical Research Center, Llc	Anchorage	Alaska
United States	University of Colorado	Aurora	Colorado
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Consultants of Southeaster PA LLP	Bala-Cynwyd	Pennsylvania
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Maryland Prostate Center	Baltimore	Maryland
United States	Union Memorial Hospital	Baltimore	Maryland
United States	Alta Bates Summit Medical Center	Berkeley	California
United States	National Cancer Institute - Center for Cancer Research	Bethesda	Maryland
United States	Walter Reed Army Medical Center	Bethesda	Maryland
United States	St. Alexius Medical Center	Bismarck	North Dakota
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Manatee Medical Research Institute, LLC	Bradenton	Florida
United States	Brooklyn Urology Research Group	Brooklyn	New York
United States	Gabrail Cancer Center	Canton	Ohio
United States	Ralph H Johnson VAMC	Charleston	South Carolina
United States	Presbyterian Hospital Center for Cancer Research	Charlotte	North Carolina
United States	Jesse Brown VA	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	North Idaho Urology	Coeur d'Alene	Idaho
United States	WJB Dorn VA Medical Center	Columbia	South Carolina
United States	Columbus Urology Research	Columbus	Ohio
United States	Northeast Urology Research	Concord	North Carolina
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Urology Clinics of North Texas	Dallas	Texas
United States	The Urology Center of Colorado	Denver	Colorado
United States	Durham VA Medical Center	Durham	North Carolina
United States	Regional Cancer Care PA	Durham	North Carolina
United States	Florida Urology Physicians	Fort Myers	Florida
United States	Myron Murdock M.D. LLC	Greenbelt	Maryland
United States	Greenville Hospital System	Greenville	South Carolina
United States	First Urology PSC	Jeffersonville	Indiana
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	University of TN Medical Center	Knoxville	Tennessee
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Urological Associates Of Lancaster	Lancaster	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Prostate Oncology Specialists, Inc.	Marina Del Rey	California
United States	The West Clinic, P.C.	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Delaware Valley Urology LLC - Westhampton	Mount Laurel	New Jersey
United States	James H. Quillen Veterans Affairs Medical Center	Mountain Home	Tennessee
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates, PC	Nashville	Tennessee
United States	The Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	Tulane University	New Orleans	Louisiana
United States	University Urology Associates	New York	New York
United States	Virginia Oncology Associates PC	Norfolk	Virginia
United States	GU Research Network, LLC	Omaha	Nebraska
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Cancer Pavillion	Pittsburgh	Pennsylvania
United States	Hudson Valley Urology, P.C.	Poughkeepsie	New York
United States	Desert Hematology-Oncology	Rancho Mirage	California
United States	VA Sierra Nevada HealthCare System	Reno	Nevada
United States	Mayo Clinic	Rochester	Minnesota
United States	Pinellas Urology, Inc.	Saint Petersburg	Florida
United States	W.G. (Bill) Hefner VA Medical Center	Salisbury	North Carolina
United States	Salt Lake Research	Salt Lake City	Utah
United States	University of Utah	Salt Lake City	Utah
United States	San Bernardino Urological Associates	San Bernardino	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	Scottsdale Healthcare	Scottsdale	Arizona
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Willamette Valley Cancer Center	Springfield	Oregon
United States	Stanford Advanced Medical Center	Stanford	California
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Madigan Army Medical Center	Tacoma	Washington
United States	James A Haley Veteran Affairs Medical Center	Tampa	Florida
United States	Central Texas Veterans Health Care System	Temple	Texas
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Washington Cancer Institute	Washington	District of Columbia
United States	The Iowa Clinic, PC Iowa Urology	West Des Moines	Iowa
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	The Schiffler Cancer Center	Wheeling	West Virginia
United States	White River Junction Veterans Affairs Medical Center	White River Junction	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
Bavarian Nordic

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  Estonia,  France,  Germany,  Iceland,  Israel,  Netherlands,  Poland,  Puerto Rico,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	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.	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	Number of Subjects Alive Without Event at 6 Months	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.	Randomization through Week 25/End of Treatment visit.