Effectiveness of Zometa® treatment for the prevention of bone metastases in high risk prostate cancer patients: a randomised, open-label, multicentre study of the European Association of Urology (EAU) in Cooperation with the Scandinavian Prostate Cancer Group (SPCG) and the Arbeitsgemeinschaft Urologische Onkologie (AUO)

ISRCTN	ISRCTN66626762
DOI	https://doi.org/10.1186/ISRCTN66626762
EudraCT/CTIS number	2004-001786-18
Secondary identifying numbers	CZOL446G DE08; NTR355

Submission date: 19/12/2005
Registration date: 19/12/2005
Last edited: 20/04/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr C Caris
Scientific

CuraTrial SMO & Research
P.O. Box 30016
Arnhem
6803 AA
Netherlands

Phone	+31 (0)26 3890677
Email	c.caris@uroweb.org

Study information

Study design	Multicentre randomised controlled parallel group trial
Primary study design	Interventional
Secondary study design	Randomised parallel trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Effectiveness of Zometa® treatment for the prevention of bone metastases in high risk prostate cancer patients: a randomised, open-label, multicentre study of the European Association of Urology (EAU) in Cooperation with the Scandinavian Prostate Cancer Group (SPCG) and the Arbeitsgemeinschaft Urologische Onkologie (AUO)
Study acronym	ZEUS
Study objectives	Zoledronic acid (Zometa®) is a third-generation nitrogen-containing bisphosphonate which has been approved in Europe and the US for the treatment of bone metastases (4 mg Zoledronic acid intravenous [iv]/month) in a broad range of tumours and for the treatment of malignancy-related hypercalcaemia. In animal models, bisphosphonates have been shown to reduce and even to prevent the development of bone metastases. The hypothetical mechanisms for this antitumour effect by bisphosphonates are: 1. The inhibition of osteoclastic bone resorption prevents the release of tumour-promoting growth factors from the bone matrix 2. Inhibition of the adhesion of tumour cells to bone matrix 3. Inducing tumour cell apoptosis It is expected that in the present study Zometa® in addition to the prevention of bone metastases will show its potential in preventing hormone therapy induced bone loss. On 20/04/2015 the following changes were made to the trial record: 1. The overall trial end date was changed from 15/01/2011 to 17/01/2014. 2. The following countries were added to the countries of recruitment: Germany, Denmark, Sweden, Norway, Finland, Belgium, Greece, Italy, Turkey, Switzerland, France, Spain
Ethics approval(s)	Ethics approval received from local medical ethics committee
Health condition(s) or problem(s) studied	Prostate cancer
Intervention	Patients will be randomised between standard treatment plus Zometa®; 4 mg infusions every 3 months for a total of 48 months or standard treatment only.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Zometa®
Primary outcome measure	The primary outcome parameter is the proportion of patients who develop bone metastases during the study.
Secondary outcome measures	1. Time to first bone metastasis 2. Overall survival 3. Time to PSA doubling 4. Safety 5. Bone mineral density (sub study in selected centres) 6. Biochemical markers of bone turnover (sub study in selected centres only)
Overall study start date	15/01/2004
Completion date	17/01/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target number of participants	1300
Key inclusion criteria	1. Male patients aged 18+ years, Eastern Cooperative Oncology Group (ECOG) = 0 (Karnofsky performance status greater than 90) 2. M0 prostate cancer patients who previously received local curative treatment (e.g. surgery, radiotherapy) or no local curative treatment. Duration between local curative treatment and starting of the study drug must not be longer than 6 months. 3. At least one of the following conditions must be present: 3.1. Gleason Score 8 - 10 3.2. pN+ 3.3. Prostate specific antigen (PSA) equal to or higher than 20 ng/ml at diagnosis 4. Patients receiving androgen deprivation by orchiectomy or administration of GnRH analogue ± anti-androgens or no androgen deprivation. Hormone therapy regimen will depend on standard medical management of prostate cancer patients i.e. when corresponding to standard medical management, patients on hormone treatment at study entry can later be withdrawn and patients not on hormone treatment at study entry can later start with androgen deprivation. Intermittent hormone treatment is allowed when corresponding to standard medical management. Patients should not be under hormonal ablation for longer than 6 months before the first study drug infusion. Neoadjuvant androgen deprivation is allowed as long as the duration between start of androgen deprivation and start of study drug is no longer than 6 months. 5. Life expectancy of greater than 6 months 6. Signed informed consent prior to initiation of any study procedure
Key exclusion criteria	1. Patients with known visceral metastasis or bone metastases in bone scan 2. Prior treatment with bisphosphonates 3. Chemotherapy to treat prostate carcinoma 4. Anti-androgen monotherapy is not allowed 5. Use of other investigational drugs (drugs not marketed for any indication) within 6 months before start of study 6. History of noncompliance to medical regimens and patients who are considered potentially unreliable or incapable of giving informed consent as judged by the investigator 7. Serum creatinine greater than 3 mg/dl (265 µmol/l) 8. History of other malignant neoplasm within previous five years with exception of non-melanomatous skin cancer which has been satisfactorily treated 9. Other known concurrent, severe medical disorder jeopardising the life of the patient in the immediate future (myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure)
Date of first enrolment	15/01/2004
Date of final enrolment	15/01/2011

Locations

Countries of recruitment

Belgium
Denmark
Finland
France
Germany
Greece
Italy
Netherlands
Norway
Spain
Sweden
Switzerland
Türkiye

Study participating centre

CuraTrial SMO & Research

Arnhem
6803 AA
Netherlands

Sponsor information

European Association of Urology (The Netherlands)
Research organisation

P.O. Box 30016
Arnhem
6803 AA
Netherlands

Phone	+31 (0)26 3890680
Email	EAU@uroweb.org
"ROR"	https://ror.org/00m9mc973

Funders

Funder type

Not defined

Not provided at time of registration

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/03/2015		Yes	No