Trial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CureVac AG
ClinicalTrials.gov Identifier:
NCT01817738
First received: February 8, 2013
Last updated: April 8, 2016
Last verified: April 2016
  Purpose
The purpose of this study is to determine whether the new RNActive®-derived prostate cancer vaccine CV9104 prolongs survival in patients with asymptomatic or minimally symptomatic metastatic prostate cancer that is castrate resistant.

Condition Intervention Phase
Prostate Cancer
Biological: CV9104
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled, Phase I/II Trial of RNActive®-Derived Cancer Vaccine (CV9104) in Asymptomatic or Minimally Symptomatic Patients With Metastatic Castrate-refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by CureVac AG:

Primary Outcome Measures:
  • Phase I (Safety Lead-In): Occurrence of dose-limiting toxicity (DLT) during the first 4 weeks of treatment (after administration of 3 vaccinations and after a 1 week observation period [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

    Safety Lead in Portion:

    Patients will receive CV9104 at a starting dose of 1920 µg in weeks 1, 2 and 3. Safety lead-in patients will be observed for DLTs until 1 week after Vaccination 3 (week 4). In case no DLTs will be observed vaccinations will continue in weeks 5, 7, 9, 12, 15, 18 and 24, then every 6 weeks for up to 12 months after the first vaccination and then every 3 months thereafter until one of the criteria for study treatment discontinuation is met


  • Phase II (Randomised Portion): Overall Survival from time of randomisation- up to 3.5-4 years. [ Time Frame: Overall survival will be assessed during the lifetime of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival from date of randomisation [ Time Frame: Every 3 months for up to 2 years ] [ Designated as safety issue: No ]
  • Progression free survival from start of first subsequent systemic therapy [ Time Frame: Every 6 months until 2 years ] [ Designated as safety issue: No ]
  • Percent change to maximal and to minimal PSA from baseline and before start of first subsequent systemic cancer therapy and from start of first systemic therapy to end of first subsequent systemic therapy [ Time Frame: Every 3 months up to 2 years ] [ Designated as safety issue: No ]
  • Cellular and humoral immune response rate against the 6 antigens encoded by CV9104 [ Time Frame: Immune responses will be assessed at baseline, in week 6 and week 24 after start of vaccination ] [ Designated as safety issue: No ]
  • Time to symptom progression based on FACT P score and subscores [ Time Frame: Assessments at baseline, weeks 5, 9,18, 24 and every 3 months for up to 2 years ] [ Designated as safety issue: No ]
  • Absolute change and area under the curve from baseline EQ-5D score and pain sub-score [ Time Frame: Assessments at baseline, weeks 5, 9,18, 24 and thereafter every 3 months for up to 2 years ] [ Designated as safety issue: No ]
  • Progression free survival from randomisation until second progression on first subsequent therapy [ Time Frame: Every 3 and 6 months up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 197
Study Start Date: August 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CV9104
CV9104 intradermal injection
Biological: CV9104
Intradermal injection of CV9104
Placebo Comparator: Placebo
Placebo intradermal injection
Biological: Placebo
Intradermal injection of placebo

Detailed Description:

The study is the first clinical study with the new prostate cancer vaccine CV9104. This vaccine is composed of 6RNActive®-based compounds, each encoding for an antigen that is overexpressed in prostate cancer compared to healthy tissues. RNActive®-based vaccines are a novel class of vaccines based on messenger RNA.

The study is a double-blind randomized placebo-controlled phase I/II trial in men with asymptomatic- minimally symptomatic metastatic castrate-refractory prostate cancer.

The phase 1 (safety lead- in) part of the trial has the primary objective to assess the safety of CV9104 and to determine the dose for the randomized phase II part.

The primary objective of the phase II part is to compare overall survival in patients treated with CV9104 compared to patients treated with placebo.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Male, age ≥18 years
  2. Histologically confirmed castrate refractory metastatic adenocarcinoma of the prostate with progressive disease after surgical castration or during androgen suppression therapy including a GNRH agonist or antagonist and after at least 1 additional anti-hormonal manipulation; and serum testosterone level of < 50 ng/dL or < 1.7 nmol/L

    Progression will be confirmed either

    • radiologically or
    • by 2 consecutive rises of PSA, measured at least 1 week apart, resulting at least in a 50% increase over the nadir and a PSA > 2 ng/mL.
    • An antiandrogen withdrawal response must have been excluded after discontinuation of antiandrogen therapy for at least 6 weeks.
  3. Metastatic disease confirmed by imaging
  4. ECOG performance status 0 or 1

Key Exclusion Criteria:

  1. Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
  2. Treatment with any investigational anticancer agents within 4 weeks prior to first dose of study drug
  3. Systemic treatment with immunosuppressive agents
  4. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
  5. History of or current autoimmune disorders
  6. Primary or secondary immune deficiency.
  7. Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
  8. Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to WHO criteria or uncontrolled hypertension at the time of enrolment (systolic blood pressure ≥ 180 mm Hg)´
  9. Previous chemotherapy for metastatic PCA.
  10. Previous anti-hormonal treatment with abiraterone or any other investigational anti-hormonal treatment.
  11. Cancer-related pain requiring opioid narcotics within 28 days before enrolment or an average pain score of > 3 on a visual analogue scale.
  12. Presence of visceral metastases.
  13. History of other malignancies other than PCA over the last 5 years (except basal cell carcinoma of the skin).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01817738

  Hide Study Locations
Locations
Czech Republic
Krajská zdravotní, a.s. - Nemocnice Chomutov, o.z.Onkologické oddělení
Chomutov, Czech Republic, 430 12
Fakultní nemocnice Olomouc, Urologická klinika
Olomouc, Czech Republic, 779 00
Multiscan, a.s, Oddělení klinické a radiační onkologie
Pardubice, Czech Republic, 532 03
Thomayerova nemocnice, Urologické oddělení
Praha, Czech Republic, 140 59
Krajská zdravotní, a.s. - Masarykova nemocnice Ústí nad Labem
Usti nad Labem, Czech Republic, 401 13
France
Institut Gustave Roussy
Villejuif cedex, France, 94805
Germany
Universitätsklinikum Aachen Klinik für Urologie
Aachen, Germany, D-52074
Vivantes Klinikum Am Urban Klinik für Urologie
Berlin, Germany, D-10967
Medizinisches Zentrum Friedensplatz
Bonn, Germany, 53111
Universitätsklinikum Dresden Klinik und Poliklinik für Urologie
Dresden, Germany, D-01307
Chirurgische Universitätsklinik Freiburg Klinik für Urologie
Freiburg, Germany, D-79106
Urologikum Hamburg
Hamburg, Germany, 22081
Nationales Zentrum für Tumorerkrankungen Medizinische Onkologie
Heidelberg, Germany, D-69120
Urologie am Nordplatz
Leipzig, Germany, 04105
UMM Universitätsmedizin Mannheim
Mannheim, Germany, 68167
Praxis Dr.schulze
Marklleeberg, Germany, 04416
Urologische Klinik und Poliklinik der Technischen Universität München Klinikum Rechts der Isar
Munich, Germany, D-81675
Universitätsklinikum Münster Klinik und Poliklinik für Urologie
Münster, Germany, D-48149
Studienpraxis für Urologie
Nürtingen, Germany, D-72622
Ortenau Klinikum Urologie und Kinderurologie
Offenburg, Germany, 77654
Urologische Klinik Dr. Castingius München
Planegg, Germany, 82152
Universitätsklinik für Urologie
Tübingen, Germany, D-72076
Poland
Medica Pro Familia Krakow
Krakow, Poland, 30-002
Centrum Urologiczne Sp. z o.o.
Mysłowice, Poland, 41-400
NZOZ Magodent, Centrum Medyczne Ostrobramska, Oncologii Klinicznej i Chemíoterapii
Warsaw, Poland, 04-125
Centralny Szpital Kliniczny MSWiA, Klinika Onkologii I Hematologii
Warsaw, Poland, 02-507
Szpital Sw. Elżbiety - Mokotowskie Centrum Medyczne
Warsaw, Poland, 02-616
Instytut M. Curie-Skłodowskiej Centrum Onkologii
Warsaw, Poland, 02-781
Profesorskie Centrum Medyczne OPTIMUM Wrocław
Wroclaw, Poland, 50-421
Szpital Uniwersytecki, Katedra i Klinika Urologii i Onkologii Urologicznej
Wroclaw, Poland, 50-556
Spain
Hospital de Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal (CIOCC)
Madrid, Spain, 28050
Hospital Clínico Virgen de la Victoria Campus Universitario de Teatinos s/n
Malaga, Spain, 29010
Clínica Universitaria de Navarra Departamento de Oncología
Pamplona, Spain, 31008
Complejo Hospitalario Universitario Santiago Departamento de Oncología
Santiago de Compostela, Spain, 15703
Instituto Valenciano de Oncología Unidad de Investigación Clínica
Valencia, Spain, 46009
Sweden
"Sahlgrenska Universitetssjukhuset Urologmottagningen
Gothenburg, Sweden, 41345
Skånes Universitetssjukhus Malmö Urologmottagningen
Malmö, Sweden, 20502
Karolinska Universitetssjukhuset Solna Urologiska kliniken
Stockholm, Sweden, 17176
Akademiska sjukhuset Urologmottagningen
Uppsala, Sweden, 75185
Universitetssjukhuset Örebro Urologmottagningen
Örebro, Sweden, 70185
Switzerland
Universitätsspital Basel Medizinische Onkologie
Basel, Switzerland, 4031
Kantonsspital Graubünden Department Innere Medizin Hämatologie und Onkologie
Chur, Switzerland, 7000
CHUV Centre Pluridisciplinaire d'Oncologie
Lausanne, Switzerland, 1011
Kantonsspital St. Gallen Department Innere Medizin Hämatologie Medizinische Onkologie
St. Gallen, Switzerland, 9007
United Kingdom
Royal Free Hospital
London, United Kingdom, NW32QC
Nottingham City Hospital Department of Oncology
Nottingham, United Kingdom, NG5 1PB
Clatterbridge Cancer Centre
Wirral, Merseyside, United Kingdom, CH63 4JY
York Hospital
York, United Kingdom, Y03 8HE
Sponsors and Collaborators
CureVac AG
Investigators
Principal Investigator: Arnulf Stenzl, Prof. Dr. University Hospital of Tübingen; Dept. of Urology
  More Information

Additional Information:
Responsible Party: CureVac AG
ClinicalTrials.gov Identifier: NCT01817738     History of Changes
Other Study ID Numbers: CV-9104-004 
Study First Received: February 8, 2013
Last Updated: April 8, 2016
Health Authority: Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by CureVac AG:
Metastatic
Castrate-refractory

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on July 28, 2016