Phase III Study of DCVAC/PCa Added to Standard Chemotherapy for Men With Metastatic Castration Resistant Prostate Cancer

NCT ID: NCT02111577

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-26
• Study Completion Date: 2020-01-28

Brief Summary

The VIABLE study sought to confirm the hypothesis that the combination of docetaxel with DCVAC/PCa followed by a maintenance therapy with DCVAC/PCa would improve overall survival in patients with metastatic castration-resistant prostate cancer.

Detailed Description

This was a randomized, double blind, placebo-controlled, multicenter, international, parallel-group phase III study. Patients with metastatic castration-resistant prostate cancer who were candidates to receive standard of care first-line chemotherapy with docetaxel plus prednisone were randomized 2:1 into one of two arms: an investigational arm (DCVAC/PCa) and a control arm (placebo) in addition to chemotherapy (docetaxel plus prednisone).

Conditions

Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

DCVAC/PCa with standard of care chemotherapy

Combination therapy with DCVAC/PCa and standard of care chemotherapy (docetaxel and prednisone)

Group Type: EXPERIMENTAL

DCVAC/PCa

Intervention Type: BIOLOGICAL

DCVAC/PCa concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). DCVAC/PCa was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of DCVAC/PCa was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.

Placebo with standard of care chemotherapy

Combination therapy with placebo and standard of care chemotherapy (docetaxel and prednisone) as comparator

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). Placebo was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of placebo was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.

Interventions

DCVAC/PCa

DCVAC/PCa concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). DCVAC/PCa was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of DCVAC/PCa was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.

Intervention Type: BIOLOGICAL

Placebo

Placebo concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). Placebo was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of placebo was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.

Intervention Type: BIOLOGICAL

Other Intervention Names

Stapuldencel

Eligibility Criteria

Inclusion Criteria

• Male 18 years and older.
• Histologically or cytologically confirmed prostate adenocarcinoma.
• Presence of skeletal, or soft-tissue/visceral/nodal metastases according to one of the following criteria:

• Confirmed pathological fracture related to the disease OR
• Confirmation of distant bone and/or soft-tissue and/or visceral metastases on CT or MRI scan or bone scintigraphy OR
• Positive pathology report of metastatic lesion
• Disease progression despite androgen-deprivation therapy (ADT) as indicated by:

• Prostate-specific antigen (PSA) increase that is ≥ 2 ng/mL and ≥ 25% above the minimum PSA as reached during ADT or above the pre-treatment level, if no response was observed and which is confirmed by a second value 1 or more weeks later OR
• Progression of measurable lymph nodes (short axis ≥ 15 mm) or visceral lesion measurable per RECIST v1.1 criteria, confirmation by an independent review facility (IRF) required OR
• Two or more new lesions appearing on bone scan/imaging compared with a previous scan (confirmation by IRF required)
• Maintenance of castrate conditions: patients, who have not had a surgical orchiectomy, must continue with hormone therapy with gonadotropin releasing hormone/ luteinizing hormone-releasing hormone (GnRH/LHRH) agonists or antagonists to reach levels of serum testosterone of ≤ 1.7 nmol/L (50 ng/dL). The duration of the castration period must be at least 4 months before screening as evidenced by combination of clinical/laboratory data (see section 6.8.1).
• Laboratory criteria:

• White blood cells (WBC) greater than 4,000/mm3 (4.0 x109/L)
• Neutrophil count greater than 1,500/mm3 (1.5 x109/L).
• Hemoglobin of at least 10 g/dL (100 g/L).
• Platelet count of at least 100,000/mm3 (100 x 109/L).
• Total bilirubin within normal limits (benign hereditary hyperbilirubinemias, e.g. Gilbert's syndrome, are permitted).
• Serum alanine aminotransferase, aspartate aminotransferase, and creatinine < 1.5x times the upper limit of normal (ULN).
• Life expectancy of at least 6 months based on Investigator's judgment.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
• At least 4 weeks after surgery or radiotherapy before randomization.
• A minimum of 28 days beyond initiation of bisphosphonate or denosumab therapy before randomization.
• Recovery from primary local surgical treatment, radiotherapy or orchiectomy before randomization.
• Signed informed consent including patient's ability to comprehend its contents.

Exclusion Criteria

• Confirmed brain and/or leptomeningeal metastases (other visceral metastases are acceptable).
• Current symptomatic spinal cord compression requiring surgery or radiation therapy.
• Prior chemotherapy for prostate cancer.
• Patient co-morbidities:

• Subjects who are not indicated for chemotherapy treatment with first line Standard of Care chemotherapy (docetaxel and prednisone).
• HIV positive, human T-lymphotropic virus positive.
• Active hepatitis B (active hepatitis B), active hepatitis C (HCV), active syphilis.
• Evidence of active bacterial, viral or fungal infection requiring systemic treatment.
• Clinically significant cardiovascular disease including:

• symptomatic congestive heart failure.
• unstable angina pectoris.
• serious cardiac arrhythmia requiring medication.
• uncontrolled hypertension.
• myocardial infarction or ventricular arrhythmia or stroke within a 6 months before screening, known left ventricular ejection fraction (LVEF) < 40% or serious cardiac conduction system disorders, if a pacemaker is not present.
• Pleural and pericardial effusion of any NCI CTCAE grade.
• Peripheral neuropathy having a NCI CTCAE ≥ grade 2.
• History of malignant disease (with the exception of non-melanoma skin tumors) in the preceding five years.
• Active autoimmune disease requiring treatment.
• History of severe forms of primary immune deficiencies.
• History of anaphylaxis or other serious reaction following vaccination.
• Known hypersensitivity to any constituent of the DCVAC/PCa or placebo product.
• Uncontrolled co-morbidities including, psychiatric or social conditions which, in the Investigator's opinion, would prevent participation in the trial.
• Systemic corticosteroids at doses greater than 40 mg hydrocortisone daily or equivalent for any reason other than treatment of PCa within 6 months before randomization.
• Ongoing systemic immunosuppressive therapy for any reason.
• Treatment with anti-androgens, inhibitors of adrenal-produced androgens or other hormonal tumor-focused treatment performed on the day of randomization (except for GnRH/LHRH agonists or antagonists) to exclude possible anti-androgen withdrawal response. This criterion is not applicable to subjects who have never responded to anti-androgen treatment, as there is no risk of anti-androgen withdrawal response.
• Treatment with immunotherapy against PCa within 6 months before randomization.
• Treatment with radiopharmaceutical within 8 weeks before randomization.
• Participation in a clinical trial using non-immunological experimental therapy within 4 weeks before randomization.
• Participation in a clinical trial using immunological experimental therapy (e.g., monoclonal antibodies, cytokines or active cellular immunotherapies) within 6 months before randomization.
• Refusal to sign the informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

SOTIO a.s.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas J. Vogelzang

Role: PRINCIPAL_INVESTIGATOR

US Oncology Research/Comprehensive Cancer Centers of Nevada

Locations

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States

Ironwood Cancer & Research Centers

Chandler, Arizona, United States

Mayo Clinic

Scottsdale, Arizona, United States

Compassionate Care Research Group, Inc.

Corona, California, United States

California Cancer Associates for Research and Excellence

Encinitas, California, United States

Compassionate Care Research Group, Inc.

Fountain Valley, California, United States

St. Joseph Heritage Healthcare

Fullerton, California, United States

Hao Wei Zhang, MD, LLC

Los Angeles, California, United States

Desert Hematology Oncology Medical Group

Rancho Mirage, California, United States

Compassionate Care Research Group, Inc.

Riverside, California, United States

Sharp Clinical Oncology Research

San Diego, California, United States

Oncology Institute of Hope and Innovation

Whittier, California, United States

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

University of Colorado

Aurora, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Eastern CT Hematology and Oncololgy Associates

Norwich, Connecticut, United States

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Univ. of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Saint Luke's Cancer Institute

Kansas City, Kansas, United States

University of Kansas Cancer Center & Medical Pavilion

Westwood, Kansas, United States

Tulane University

New Orleans, Louisiana, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Associates In Oncology/Hematology,P.C

Rockville, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Umass Memorial Medical Center

Worcester, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Karmanos Cancer Center

Detroit, Michigan, United States

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

GU Research Network

Omaha, Nebraska, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Comprehensive Cancer Research Centers of Nevada

Henderson, Nevada, United States

New Jersey Hematology Oncology Associates

Brick, New Jersey, United States

Premier Urology Associates, LLC / AdvanceMed Research

Lawrenceville, New Jersey, United States

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Mount Sinai Medical Center

New York, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

UC Health University of Cincinnati

Cincinnati, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, United States

Urologic Consultants of Southeastern Pennsylvania

Bala-Cynwyd, Pennsylvania, United States

Cancer Care Associates St. Luke's University and Health Network

Easton, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Associates in Oncology & Hematology

Chattanooga, Tennessee, United States

Arlington Cancer Center

Arlington, Texas, United States

UT Health, Internal Medicine, Division of Oncology

Houston, Texas, United States

Texas Health Physicians Group

Plano, Texas, United States

Cancer Care Network of South Texas

San Antonio, Texas, United States

Tyler Hematology Oncology

Tyler, Texas, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

West Virginia University Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States

Universitatsklinikum fur Urologie und Andrologie

Salzburg, , Austria

Krankenhaus Barmherzige Brueder

Vienna, , Austria

AKH Universitatskrankenhaus Wien

Vienna, , Austria

N.N. Alexandrov National Research Center

Lesnoy, , Belarus

Minsk City Oncological Hospital

Minsk, , Belarus

Clinique d'Oncologie Medicale Institut Jules Bordet

Brussels, , Belgium

Erasme Hospital- Urologie

Brussels, , Belgium

Cliniques Universitaires Saint Luc- Urologie

Brussels, , Belgium

Urologie UZ Gent

Ghent, , Belgium

Urology Department St. Elizabeth Ziekenhuis

Turnhout, , Belgium

Specialized Hospital for Active treatment in Oncology

Haskovo, , Bulgaria

Central Oncology Hospital

Plovdiv, , Bulgaria

Complex Oncology Center

Plovdiv, , Bulgaria

Multifunctional Hospital for Active Treatment Serdika

Sofia, , Bulgaria

Specialized Hospital for Active Treatment of Oncology Diseases

Sofia, , Bulgaria

General Hospital Varazdin

Varaždin, , Croatia

Clinical Hospital Center Zagreb

Zagreb, , Croatia

University Hospital Center Sisters of Charity

Zagreb, , Croatia

Onkologicke centrum, Nemocnice Chomutov

Chomutov, , Czechia

Klinika onkologie a radioterapie, Fakultni nemocnice

Hradec Králové, , Czechia

Nemocnice Jihlava, urologicke oddeleni

Jihlava, , Czechia

Urologicke oddeleni, Krajska nemocnice

Liberec, , Czechia

Onkologicka klinika, Fakultni nemocnice

Olomouc, , Czechia

Klinika onkologicka, Fakultni nemocnice

Ostrava-Poruba, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Thomayerova nemocnice

Prague, , Czechia

Fakultni nemocnice v Motole

Prague, , Czechia

Krajska zdravotni, urologicke oddeleni

Ústí nad Labem, , Czechia

Rigshospitalet

Copenhagen, , Denmark

St-Louis IDF Medical Oncology

Paris, , France

Hopital St. Joseph

Paris, , France

Hospital Cochin, Service de Urologie

Paris, , France

HEGP medical oncology

Paris, , France

HIA Begin

Saint-Mandé, , France

Hospital Civil de Strasbourg

Strasbourg, , France

Charite Universitatsklinikum Berlin

Berlin, , Germany

Stadtisches Klinikum Braunschweig

Braunschweig, , Germany

Klinik und Poliklinik Urologie

Cologne, , Germany

Universtatsklinikum Carl Gustav Carus

Dresden, , Germany

Waldkrankenhaus St. Marien

Erlangen, , Germany

Krankenhaus Nordwest

Frankfurt, , Germany

Universitatsklinikum Halle (Saale)

Halle, , Germany

Asklepios-Klinik Hamburg-Altona

Hamburg, , Germany

Vinzenkrankenhaus Hannover

Hanover, , Germany

Medizinische hochschule Hannover

Hanover, , Germany

Universitatskinikum Jena

Jena, , Germany

Universitatsmedizin Mannheim

Mannheim, , Germany

Universtatsklinikum Munster

Münster, , Germany

Studienpraxis Urologie

Nürtingen, , Germany

Klinikum Oldenburg AOR

Oldenburg, , Germany

Universitastsklinikum Tubingen

Tübingen, , Germany

Universitatsklinikum Ulm

Ulm, , Germany

Ammerland Klinik fur Urologie

Westerstede, , Germany

Praxigemeinschaft fur Onkologie und Urologie

Wilhelmshaven, , Germany

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointeszet

Budapest, , Hungary

Bajcsy-Zsilinsky Korhaz

Budapest, , Hungary

Jasz-Nagykun-Szolnok Megyei

Szolnok, , Hungary

CRO Aviano

Aviano, , Italy

A.O.U. Policlinico Vittorio Emanuele

Catania, , Italy

A.O. Istituti Ospitalieri di Cremona

Cremona, , Italy

A.O. Santa Croce e Carle Oespedale

Cuneo, , Italy

Universita di Roma Sapienza

Rome, , Italy

Azienda Ospedialiera Universitaria Senese

Siena, , Italy

Oncologia medica Ospedale S. Vincenzo

Taormina, , Italy

Paula Stradina Kliniska Universitates slimnica

Riga, , Latvia

Lithuanian University of Health Science Oncology Institute

Kaunas, , Lithuania

Klaipeda University Hospital

Klaipėda, , Lithuania

Vilnius University Hospital

Vilnius, , Lithuania

National Cancer Institute

Vilnius, , Lithuania

VU medical Center

Amsterdam, , Netherlands

Wilhemina Ziekenhuis

Assen, , Netherlands

Tergooi Ziekenhuizen

Hilversum, , Netherlands

Spaarne Gasthuis

Hoofddorp, , Netherlands

Oncology Medisch Centrum

Leeuwarden, , Netherlands

UMC St.Radboud

Nijmegen, , Netherlands

Oncology Maasstad Ziekenhuis

Rotterdam, , Netherlands

Przychodnia Lekarska (KOMED)

Konin, , Poland

Szpital im M.Kopernika

Lodz, , Poland

INSTYTUT im. Marii Sklodowskiej-Curie

Warsaw, , Poland

Centrum Medyczne Ostrobramska

Warsaw, , Poland

Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego

Wroclaw, , Poland

Hospital da Luz

Lisbon, , Portugal

Centro Hospitalar de Lisboa Norte, E.P.E - Hospital de Santa Maria

Lisbon, , Portugal

Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E

Porto, , Portugal

CHC Zemun

Belgrade, , Serbia

Clinical Center of Serbia

Belgrade, , Serbia

Institute of Oncology and Radiology of Serbia

Belgrade, , Serbia

KBC Bezanijska Kosa

Belgrade, , Serbia

J.Breza MEDICAL s.r.o.

Bratislava, , Slovakia

Urologicka ambulancia CUIMED s.r.o.

Bratislava, , Slovakia

Univerzitna nemocnica Martin

Martin, , Slovakia

Urologicka ambulancia Uroexam, spol. s r.o.

Nitra, , Slovakia

UROX s.r.o.

Piešťany, , Slovakia

Urocentrum MILAB s.r.o.

Prešov, , Slovakia

Privatna urologicka ambulancia

Trenčín, , Slovakia

Fakultna nemocnica s poliklinikou Zilina

Žilina, , Slovakia

Hospital Universitario Príncipe de Asturias

Alcalá de Henares, , Spain

Hospital Clinic I Provincial de Barcelona

Barcelona, , Spain

Hospital General Universitario Gregorio Maranón

Madrid, , Spain

Hosp. Clinico Univ. San Carlos

Madrid, , Spain

Instituto de Investigaciones Sanitarias (IIS), Fundacíon Jimenez Díaz (FJD)

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, , Spain

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, , Spain

Hospital Carlos Haya

Málaga, , Spain

Hospital Universitario Quiron Madrid

Pozuelo de Alarcón, , Spain

Örebro University Hospital

Örebrö, , Sweden

University Hospital Umeå, Dept Oncology

Umeå, , Sweden

The Clatterbridge Cancer Centre

Bebington, , United Kingdom

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

St. Luke's Cancer Centre Royal Surrey County Hospital NHS Foundation Trust

Guildford, , United Kingdom

Royal Free Hospital

London, , United Kingdom

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Northern Centre for Cancer Care, Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Countries

United States; Austria; Belarus; Belgium; Bulgaria; Croatia; Czechia; Denmark; France; Germany; Hungary; Italy; Latvia; Lithuania; Netherlands; Poland; Portugal; Serbia; Slovakia; Spain; Sweden; United Kingdom

References

Hensler M, Rakova J, Kasikova L, Lanickova T, Pasulka J, Holicek P, Hraska M, Hrnciarova T, Kadlecova P, Schoenenberger A, Sochorova K, Rozkova D, Sojka L, Drozenova J, Laco J, Horvath R, Podrazil M, Hongyan G, Brtnicky T, Halaska MJ, Rob L, Ryska A, Coosemans A, Vergote I, Garg AD, Cibula D, Bartunkova J, Spisek R, Fucikova J. Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines. Oncoimmunology. 2022 Jul 22;11(1):2101596. doi: 10.1080/2162402X.2022.2101596. eCollection 2022.

Reference Type: DERIVED

PMID: 35898703 (View on PubMed)

Vogelzang NJ, Beer TM, Gerritsen W, Oudard S, Wiechno P, Kukielka-Budny B, Samal V, Hajek J, Feyerabend S, Khoo V, Stenzl A, Csoszi T, Filipovic Z, Goncalves F, Prokhorov A, Cheung E, Hussain A, Sousa N, Bahl A, Hussain S, Fricke H, Kadlecova P, Scheiner T, Korolkiewicz RP, Bartunkova J, Spisek R; VIABLE Investigators. Efficacy and Safety of Autologous Dendritic Cell-Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer: The VIABLE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):546-552. doi: 10.1001/jamaoncol.2021.7298.

Reference Type: DERIVED

PMID: 35142815 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-002814-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SP005

Identifier Type: -

Identifier Source: org_study_id