Back to resultsTrial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CV9104
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Metastatic, Castrate-refractory
Eligibility Criteria
Key Inclusion Criteria:
- Male, age ≥18 years
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.
- Metastatic disease confirmed by imaging
- ECOG performance status 0 or 1
Key Exclusion Criteria:
- Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
- Treatment with any investigational anticancer agents within 4 weeks prior to first dose of study drug
- Systemic treatment with immunosuppressive agents
- 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.
- History of or current autoimmune disorders
- Primary or secondary immune deficiency.
- Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
- 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)´
- Previous chemotherapy for metastatic PCA.
- Previous anti-hormonal treatment with abiraterone or any other investigational anti-hormonal treatment.
- Cancer-related pain requiring opioid narcotics within 28 days before enrolment or an average pain score of > 3 on a visual analogue scale.
- Presence of visceral metastases.
- History of other malignancies other than PCA over the last 5 years (except basal cell carcinoma of the skin).
Sites / Locations
- Krajská zdravotní, a.s. - Nemocnice Chomutov, o.z.Onkologické oddělení
- Fakultní nemocnice Olomouc, Urologická klinika
- Multiscan, a.s, Oddělení klinické a radiační onkologie
- Thomayerova nemocnice, Urologické oddělení
- Krajská zdravotní, a.s. - Masarykova nemocnice Ústí nad Labem
- Institut Gustave Roussy
- Universitätsklinikum Aachen Klinik für Urologie
- Vivantes Klinikum Am Urban Klinik für Urologie
- Medizinisches Zentrum Friedensplatz
- Universitätsklinikum Dresden Klinik und Poliklinik für Urologie
- Chirurgische Universitätsklinik Freiburg Klinik für Urologie
- Urologikum Hamburg
- Nationales Zentrum für Tumorerkrankungen Medizinische Onkologie
- Urologie am Nordplatz
- UMM Universitätsmedizin Mannheim
- Praxis Dr.schulze
- Urologische Klinik und Poliklinik der Technischen Universität München Klinikum Rechts der Isar
- Universitätsklinikum Münster Klinik und Poliklinik für Urologie
- Studienpraxis für Urologie
- Ortenau Klinikum Urologie und Kinderurologie
- Urologische Klinik Dr. Castingius München
- Universitätsklinik für Urologie
- Medica Pro Familia Krakow
- Centrum Urologiczne Sp. z o.o.
- Centralny Szpital Kliniczny MSWiA, Klinika Onkologii I Hematologii
- Szpital Sw. Elżbiety - Mokotowskie Centrum Medyczne
- Instytut M. Curie-Skłodowskiej Centrum Onkologii
- NZOZ Magodent, Centrum Medyczne Ostrobramska, Oncologii Klinicznej i Chemíoterapii
- Profesorskie Centrum Medyczne OPTIMUM Wrocław
- Szpital Uniwersytecki, Katedra i Klinika Urologii i Onkologii Urologicznej
- Hospital de Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal (CIOCC)
- Hospital Clínico Virgen de la Victoria Campus Universitario de Teatinos s/n
- Clínica Universitaria de Navarra Departamento de Oncología
- Complejo Hospitalario Universitario Santiago Departamento de Oncología
- Instituto Valenciano de Oncología Unidad de Investigación Clínica
- "Sahlgrenska Universitetssjukhuset Urologmottagningen
- Skånes Universitetssjukhus Malmö Urologmottagningen
- Karolinska Universitetssjukhuset Solna Urologiska kliniken
- Akademiska sjukhuset Urologmottagningen
- Universitetssjukhuset Örebro Urologmottagningen
- Universitätsspital Basel Medizinische Onkologie
- Kantonsspital Graubünden Department Innere Medizin Hämatologie und Onkologie
- CHUV Centre Pluridisciplinaire d'Oncologie
- Kantonsspital St. Gallen Department Innere Medizin Hämatologie Medizinische Onkologie
- Royal Free Hospital
- Nottingham City Hospital Department of Oncology
- Clatterbridge Cancer Centre
- York Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
CV9104
Placebo
Arm Description
CV9104 intradermal injection
Placebo intradermal injection
Outcomes
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
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.
Secondary Outcome Measures
Progression free survival from date of randomisation
Progression free survival from start of first subsequent systemic therapy
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
Cellular and humoral immune response rate against the 6 antigens encoded by CV9104
Time to symptom progression based on FACT P score and subscores
Absolute change and area under the curve from baseline EQ-5D score and pain sub-score
Progression free survival from randomisation until second progression on first subsequent therapy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01817738
Brief Title
Trial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Why Stopped
Follow up period after primary analysis was prematurely stopped because more mature data will not impact the study outcome
Study Start Date
August 2012 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CureVac
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Metastatic, Castrate-refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
197 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CV9104
Arm Type
Active Comparator
Arm Description
CV9104 intradermal injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo intradermal injection
Intervention Type
Biological
Intervention Name(s)
CV9104
Intervention Description
Intradermal injection of CV9104
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Intradermal injection of placebo
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
Up to 4 weeks
Title
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
Secondary Outcome Measure Information:
Title
Progression free survival from date of randomisation
Time Frame
Every 3 months for up to 2 years
Title
Progression free survival from start of first subsequent systemic therapy
Time Frame
Every 6 months until 2 years
Title
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
Title
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
Title
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
Title
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
Title
Progression free survival from randomisation until second progression on first subsequent therapy
Time Frame
Every 3 and 6 months up to 2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male, age ≥18 years
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.
Metastatic disease confirmed by imaging
ECOG performance status 0 or 1
Key Exclusion Criteria:
Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
Treatment with any investigational anticancer agents within 4 weeks prior to first dose of study drug
Systemic treatment with immunosuppressive agents
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.
History of or current autoimmune disorders
Primary or secondary immune deficiency.
Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
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)´
Previous chemotherapy for metastatic PCA.
Previous anti-hormonal treatment with abiraterone or any other investigational anti-hormonal treatment.
Cancer-related pain requiring opioid narcotics within 28 days before enrolment or an average pain score of > 3 on a visual analogue scale.
Presence of visceral metastases.
History of other malignancies other than PCA over the last 5 years (except basal cell carcinoma of the skin).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arnulf Stenzl, Prof. Dr.
Organizational Affiliation
University Hospital of Tübingen; Dept. of Urology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Krajská zdravotní, a.s. - Nemocnice Chomutov, o.z.Onkologické oddělení
City
Chomutov
ZIP/Postal Code
430 12
Country
Czech Republic
Facility Name
Fakultní nemocnice Olomouc, Urologická klinika
City
Olomouc
ZIP/Postal Code
779 00
Country
Czech Republic
Facility Name
Multiscan, a.s, Oddělení klinické a radiační onkologie
City
Pardubice
ZIP/Postal Code
532 03
Country
Czech Republic
Facility Name
Thomayerova nemocnice, Urologické oddělení
City
Praha
ZIP/Postal Code
140 59
Country
Czech Republic
Facility Name
Krajská zdravotní, a.s. - Masarykova nemocnice Ústí nad Labem
City
Usti nad Labem
ZIP/Postal Code
401 13
Country
Czech Republic
Facility Name
Institut Gustave Roussy
City
Villejuif cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Universitätsklinikum Aachen Klinik für Urologie
City
Aachen
ZIP/Postal Code
D-52074
Country
Germany
Facility Name
Vivantes Klinikum Am Urban Klinik für Urologie
City
Berlin
ZIP/Postal Code
D-10967
Country
Germany
Facility Name
Medizinisches Zentrum Friedensplatz
City
Bonn
ZIP/Postal Code
53111
Country
Germany
Facility Name
Universitätsklinikum Dresden Klinik und Poliklinik für Urologie
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Chirurgische Universitätsklinik Freiburg Klinik für Urologie
City
Freiburg
ZIP/Postal Code
D-79106
Country
Germany
Facility Name
Urologikum Hamburg
City
Hamburg
ZIP/Postal Code
22081
Country
Germany
Facility Name
Nationales Zentrum für Tumorerkrankungen Medizinische Onkologie
City
Heidelberg
ZIP/Postal Code
D-69120
Country
Germany
Facility Name
Urologie am Nordplatz
City
Leipzig
ZIP/Postal Code
04105
Country
Germany
Facility Name
UMM Universitätsmedizin Mannheim
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Praxis Dr.schulze
City
Marklleeberg
ZIP/Postal Code
04416
Country
Germany
Facility Name
Urologische Klinik und Poliklinik der Technischen Universität München Klinikum Rechts der Isar
City
Munich
ZIP/Postal Code
D-81675
Country
Germany
Facility Name
Universitätsklinikum Münster Klinik und Poliklinik für Urologie
City
Münster
ZIP/Postal Code
D-48149
Country
Germany
Facility Name
Studienpraxis für Urologie
City
Nürtingen
ZIP/Postal Code
D-72622
Country
Germany
Facility Name
Ortenau Klinikum Urologie und Kinderurologie
City
Offenburg
ZIP/Postal Code
77654
Country
Germany
Facility Name
Urologische Klinik Dr. Castingius München
City
Planegg
ZIP/Postal Code
82152
Country
Germany
Facility Name
Universitätsklinik für Urologie
City
Tübingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Medica Pro Familia Krakow
City
Krakow
ZIP/Postal Code
30-002
Country
Poland
Facility Name
Centrum Urologiczne Sp. z o.o.
City
Mysłowice
ZIP/Postal Code
41-400
Country
Poland
Facility Name
Centralny Szpital Kliniczny MSWiA, Klinika Onkologii I Hematologii
City
Warsaw
ZIP/Postal Code
02-507
Country
Poland
Facility Name
Szpital Sw. Elżbiety - Mokotowskie Centrum Medyczne
City
Warsaw
ZIP/Postal Code
02-616
Country
Poland
Facility Name
Instytut M. Curie-Skłodowskiej Centrum Onkologii
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
NZOZ Magodent, Centrum Medyczne Ostrobramska, Oncologii Klinicznej i Chemíoterapii
City
Warsaw
ZIP/Postal Code
04-125
Country
Poland
Facility Name
Profesorskie Centrum Medyczne OPTIMUM Wrocław
City
Wroclaw
ZIP/Postal Code
50-421
Country
Poland
Facility Name
Szpital Uniwersytecki, Katedra i Klinika Urologii i Onkologii Urologicznej
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
Facility Name
Hospital de Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal (CIOCC)
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Clínico Virgen de la Victoria Campus Universitario de Teatinos s/n
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Clínica Universitaria de Navarra Departamento de Oncología
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Complejo Hospitalario Universitario Santiago Departamento de Oncología
City
Santiago de Compostela
ZIP/Postal Code
15703
Country
Spain
Facility Name
Instituto Valenciano de Oncología Unidad de Investigación Clínica
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
"Sahlgrenska Universitetssjukhuset Urologmottagningen
City
Gothenburg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
Skånes Universitetssjukhus Malmö Urologmottagningen
City
Malmö
ZIP/Postal Code
20502
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset Solna Urologiska kliniken
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Facility Name
Akademiska sjukhuset Urologmottagningen
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Universitetssjukhuset Örebro Urologmottagningen
City
Örebro
ZIP/Postal Code
70185
Country
Sweden
Facility Name
Universitätsspital Basel Medizinische Onkologie
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
Kantonsspital Graubünden Department Innere Medizin Hämatologie und Onkologie
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
CHUV Centre Pluridisciplinaire d'Oncologie
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Kantonsspital St. Gallen Department Innere Medizin Hämatologie Medizinische Onkologie
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW32QC
Country
United Kingdom
Facility Name
Nottingham City Hospital Department of Oncology
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Clatterbridge Cancer Centre
City
Wirral, Merseyside
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
York Hospital
City
York
ZIP/Postal Code
Y03 8HE
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.curevac.de
Description
Click here for more information about CureVac
Learn more about this trial
Trial of RNActive®-Derived Prostate Cancer Vaccine in Metastatic Castrate-refractory Prostate Cancer
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