Clinical trial NCT01817738: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: Metastatic
Castrate-refractory
Lead sponsor: CureVac
Sponsor class: INDUSTRY
First posted: 2013-03-25
Enrollment: 197
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: 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
timeFrame: Up to 4 weeks
measure: Phase II (Randomised Portion): Overall Survival from time of randomisation- up to 3.5-4 years.
timeFrame: Overall survival will be assessed during the lifetime of the study
Secondary outcomes:
measure: Progression free survival from date of randomisation
timeFrame: Every 3 months for up to 2 years
measure: Progression free survival from start of first subsequent systemic therapy
timeFrame: Every 6 months until 2 years
measure: 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
timeFrame: Every 3 months up to 2 years
measure: Cellular and humoral immune response rate against the 6 antigens encoded by CV9104
timeFrame: Immune responses will be assessed at baseline, in week 6 and week 24 after start of vaccination
measure: Time to symptom progression based on FACT P score and subscores
timeFrame: Assessments at baseline, weeks 5, 9,18, 24 and every 3 months for up to 2 years
measure: Absolute change and area under the curve from baseline EQ-5D score and pain sub-score
timeFrame: Assessments at baseline, weeks 5, 9,18, 24 and thereafter every 3 months for up to 2 years
measure: Progression free survival from randomisation until second progression on first subsequent therapy
timeFrame: Every 3 and 6 months up to 2 years
Other outcomes:
Locations:
city: Chomutov
country: Czech Republic
facility: Krajská zdravotní, a.s. - Nemocnice Chomutov, o.z.Onkologické oddělení
city: Olomouc
country: Czech Republic
facility: Fakultní nemocnice Olomouc, Urologická klinika
city: Pardubice
country: Czech Republic
facility: Multiscan, a.s, Oddělení klinické a radiační onkologie
city: Praha
country: Czech Republic
facility: Thomayerova nemocnice, Urologické oddělení
city: Usti nad Labem
country: Czech Republic
facility: Krajská zdravotní, a.s. - Masarykova nemocnice Ústí nad Labem
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen Klinik für Urologie
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban Klinik für Urologie
city: Bonn
country: Germany
facility: Medizinisches Zentrum Friedensplatz
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden Klinik und Poliklinik für Urologie
city: Freiburg
country: Germany
facility: Chirurgische Universitätsklinik Freiburg Klinik für Urologie
city: Hamburg
country: Germany
facility: Urologikum Hamburg
city: Heidelberg
country: Germany
facility: Nationales Zentrum für Tumorerkrankungen Medizinische Onkologie
city: Leipzig
country: Germany
facility: Urologie am Nordplatz
city: Mannheim
country: Germany
facility: UMM Universitätsmedizin Mannheim
city: Marklleeberg
country: Germany
facility: Praxis Dr.schulze
city: Munich
country: Germany
facility: Urologische Klinik und Poliklinik der Technischen Universität München Klinikum Rechts der Isar
city: Münster
country: Germany
facility: Universitätsklinikum Münster Klinik und Poliklinik für Urologie
city: Nürtingen
country: Germany
facility: Studienpraxis für Urologie
city: Offenburg
country: Germany
facility: Ortenau Klinikum Urologie und Kinderurologie
city: Planegg
country: Germany
facility: Urologische Klinik Dr. Castingius München
city: Tübingen
country: Germany
facility: Universitätsklinik für Urologie
city: Krakow
country: Poland
facility: Medica Pro Familia Krakow
city: Mysłowice
country: Poland
facility: Centrum Urologiczne Sp. z o.o.
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA, Klinika Onkologii I Hematologii
city: Warsaw
country: Poland
facility: Szpital Sw. Elżbiety - Mokotowskie Centrum Medyczne
city: Warsaw
country: Poland
facility: Instytut M. Curie-Skłodowskiej Centrum Onkologii
city: Warsaw
country: Poland
facility: NZOZ Magodent, Centrum Medyczne Ostrobramska, Oncologii Klinicznej i Chemíoterapii
city: Wroclaw
country: Poland
facility: Profesorskie Centrum Medyczne OPTIMUM Wrocław
city: Wroclaw
country: Poland
facility: Szpital Uniwersytecki, Katedra i Klinika Urologii i Onkologii Urologicznej
city: Madrid
country: Spain
facility: Hospital de Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal (CIOCC)
city: Malaga
country: Spain
facility: Hospital Clínico Virgen de la Victoria Campus Universitario de Teatinos s/n
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra Departamento de Oncología
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario Santiago Departamento de Oncología
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología Unidad de Investigación Clínica
city: Gothenburg
country: Sweden
facility: "Sahlgrenska Universitetssjukhuset Urologmottagningen
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus Malmö Urologmottagningen
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna Urologiska kliniken
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset Urologmottagningen
city: Örebro
country: Sweden
facility: Universitetssjukhuset Örebro Urologmottagningen
city: Basel
country: Switzerland
facility: Universitätsspital Basel Medizinische Onkologie
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden Department Innere Medizin Hämatologie und Onkologie
city: Lausanne
country: Switzerland
facility: CHUV Centre Pluridisciplinaire d'Oncologie
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen Department Innere Medizin Hämatologie Medizinische Onkologie
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital Department of Oncology
city: Wirral, Merseyside
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: York
country: United Kingdom
facility: York Hospital
Study officials:
affiliation: University Hospital of Tübingen; Dept. of Urology
name: Arnulf Stenzl, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: