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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01817738
• Other study ID #: CV-9104-004
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: February 8, 2013
• Last updated: February 15, 2017
• Start date: August 2012
• Est. completion date: January 2017

Study information

• Verified date: April 2016
• Source: CureVac AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 197
• Est. completion date: January 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• CV9104
Intradermal injection of CV9104
• Placebo
Intradermal injection of placebo

Locations

Country	Name	City	State
Czech Republic	Krajská zdravotní, a.s. - Nemocnice Chomutov, o.z.Onkologické oddelení	Chomutov
Czech Republic	Fakultní nemocnice Olomouc, Urologická klinika	Olomouc
Czech Republic	Multiscan, a.s, Oddelení klinické a radiacní onkologie	Pardubice
Czech Republic	Thomayerova nemocnice, Urologické oddelení	Praha
Czech Republic	Krajská zdravotní, a.s. - Masarykova nemocnice Ústí nad Labem	Usti nad Labem
France	Institut Gustave Roussy	Villejuif cedex
Germany	Universitätsklinikum Aachen Klinik für Urologie	Aachen
Germany	Vivantes Klinikum Am Urban Klinik für Urologie	Berlin
Germany	Medizinisches Zentrum Friedensplatz	Bonn
Germany	Universitätsklinikum Dresden Klinik und Poliklinik für Urologie	Dresden
Germany	Chirurgische Universitätsklinik Freiburg Klinik für Urologie	Freiburg
Germany	Urologikum Hamburg	Hamburg
Germany	Nationales Zentrum für Tumorerkrankungen Medizinische Onkologie	Heidelberg
Germany	Urologie am Nordplatz	Leipzig
Germany	UMM Universitätsmedizin Mannheim	Mannheim
Germany	Praxis Dr.schulze	Marklleeberg
Germany	Urologische Klinik und Poliklinik der Technischen Universität München Klinikum Rechts der Isar	Munich
Germany	Universitätsklinikum Münster Klinik und Poliklinik für Urologie	Münster
Germany	Studienpraxis für Urologie	Nürtingen
Germany	Ortenau Klinikum Urologie und Kinderurologie	Offenburg
Germany	Urologische Klinik Dr. Castingius München	Planegg
Germany	Universitätsklinik für Urologie	Tübingen
Poland	Medica Pro Familia Krakow	Krakow
Poland	Centrum Urologiczne Sp. z o.o.	Myslowice
Poland	Centralny Szpital Kliniczny MSWiA, Klinika Onkologii I Hematologii	Warsaw
Poland	Instytut M. Curie-Sklodowskiej Centrum Onkologii	Warsaw
Poland	NZOZ Magodent, Centrum Medyczne Ostrobramska, Oncologii Klinicznej i Chemíoterapii	Warsaw
Poland	Szpital Sw. Elzbiety - Mokotowskie Centrum Medyczne	Warsaw
Poland	Profesorskie Centrum Medyczne OPTIMUM Wroclaw	Wroclaw
Poland	Szpital Uniwersytecki, Katedra i Klinika Urologii i Onkologii Urologicznej	Wroclaw
Spain	Hospital de Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal (CIOCC)	Madrid
Spain	Hospital Clínico Virgen de la Victoria Campus Universitario de Teatinos s/n	Malaga
Spain	Clínica Universitaria de Navarra Departamento de Oncología	Pamplona
Spain	Complejo Hospitalario Universitario Santiago Departamento de Oncología	Santiago de Compostela
Spain	Instituto Valenciano de Oncología Unidad de Investigación Clínica	Valencia
Sweden	"Sahlgrenska Universitetssjukhuset Urologmottagningen	Gothenburg
Sweden	Skånes Universitetssjukhus Malmö Urologmottagningen	Malmö
Sweden	Universitetssjukhuset Örebro Urologmottagningen	Örebro
Sweden	Karolinska Universitetssjukhuset Solna Urologiska kliniken	Stockholm
Sweden	Akademiska sjukhuset Urologmottagningen	Uppsala
Switzerland	Universitätsspital Basel Medizinische Onkologie	Basel
Switzerland	Kantonsspital Graubünden Department Innere Medizin Hämatologie und Onkologie	Chur
Switzerland	CHUV Centre Pluridisciplinaire d'Oncologie	Lausanne
Switzerland	Kantonsspital St. Gallen Department Innere Medizin Hämatologie Medizinische Onkologie	St. Gallen
United Kingdom	Royal Free Hospital	London
United Kingdom	Nottingham City Hospital Department of Oncology	Nottingham
United Kingdom	Clatterbridge Cancer Centre	Wirral, Merseyside
United Kingdom	York Hospital	York

Sponsors (1)

Lead Sponsor	Collaborator
CureVac AG

Countries where clinical trial is conducted

Czech Republic,  France,  Germany,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 4 weeks
Primary	Phase II (Randomised Portion): Overall Survival from time of randomisation- up to 3.5-4 years.		Overall survival will be assessed during the lifetime of the study
Secondary	Progression free survival from date of randomisation		Every 3 months for up to 2 years
Secondary	Progression free survival from start of first subsequent systemic therapy		Every 6 months until 2 years
Secondary	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		Every 3 months up to 2 years
Secondary	Cellular and humoral immune response rate against the 6 antigens encoded by CV9104		Immune responses will be assessed at baseline, in week 6 and week 24 after start of vaccination
Secondary	Time to symptom progression based on FACT P score and subscores		Assessments at baseline, weeks 5, 9,18, 24 and every 3 months for up to 2 years
Secondary	Absolute change and area under the curve from baseline EQ-5D score and pain sub-score		Assessments at baseline, weeks 5, 9,18, 24 and thereafter every 3 months for up to 2 years
Secondary	Progression free survival from randomisation until second progression on first subsequent therapy		Every 3 and 6 months up to 2 years

External Links

•   Click here for more information about CureVac