Contact information
Type
Scientific
Contact name
Mr C Caris
ORCID ID
Contact details
CuraTrial SMO & Research
P.O. Box 30016
Arnhem
6803 AA
Netherlands
+31 (0)26 3890677
c.caris@uroweb.org
Additional identifiers
EudraCT/CTIS number
2004-001786-18
IRAS number
ClinicalTrials.gov number
Protocol/serial number
CZOL446G DE08; NTR355
Study information
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)
Acronym
ZEUS
Study hypothesis
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
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
Patient information sheet
Condition
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
Overall study end date
17/01/2014
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Male
Target number of participants
1300
Participant 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)
Recruitment start date
15/01/2004
Recruitment end date
15/01/2011
Locations
Countries of recruitment
Belgium, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, Turkey
Study participating centre
CuraTrial SMO & Research
Arnhem
6803 AA
Netherlands
Sponsor information
Organisation
European Association of Urology (The Netherlands)
Sponsor details
P.O. Box 30016
Arnhem
6803 AA
Netherlands
+31 (0)26 3890680
EAU@uroweb.org
Sponsor type
Research organisation
Website
ROR
Funders
Funder type
Not defined
Funder name
Not provided at time of registration
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/03/2015 | Yes | No |