|- candidate number||1552|
|- NTR Number||NTR355|
|- Date ISRCTN created||19-dec-2005|
|- date ISRCTN requested||28-okt-2005|
|- Date Registered NTR||12-sep-2005|
|- Secondary IDs||N/A |
|- Public Title||ZEUS study.|
|- Scientific Title||Effectiveness of ZometaŽ treatment for the prevention of bone metastases in high risk prostate cancer patients. A randomized, open-label, multicenter study of the European Association of Urology (EAU) in Cooperation with the Scandinavian Prostate Cancer Group (SPCG) and the Arbeitsgemeinschaft Urologische Onkologie (AUO). Protocol No. CZOL446G DE08. |
|- ACRONYM||ZEUS study|
|- Healt Condition(s) or Problem(s) studied||Prostate cancer|
|- Inclusion criteria||1. Male patients aged 18+, ECOG = 0 (Karnofsky performance status > 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:
a. Gleason Score 8-10;
c. PSA equal to or higher than 20 ng/ml at diagnosis;
4. Patients receiving androgen deprivation by orchiectomy or administration of GnRH analogue ĄÓ 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i.e. when corresponding to standard medical management, patients on hormone treatment at study entry can later be withdrawn and patients not on hormone treatment at study entry can later start with androgen deprivation.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 > 6 months;
6. Signed informed consent prior to initiation of any study procedure.
|- Exclusion criteria||1. Patients with known visceral metastasis or bone metastases in bone scan;|
2. Prior treatment with bisposphonates;
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 > 3 mg/dl (265 Ýmol/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 jeopardizing 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).
|- mec approval received||yes|
|- multicenter trial||yes|
|- planned startdate ||15-jan-2004|
|- planned closingdate||15-jan-2011|
|- Target number of participants||1300|
|- Interventions||Patients will be randomised between standard treatment plus ZometaŽ 4 mg infusions every 3 months for a total of 48 months or standard treatment only.|
|- Primary outcome||The primary outcome parameter is the proportion of patients who develop bone metastases during the study. |
|- Secondary outcome||1. Time to first bone metastasis; |
2. Overall survival;
3. Time to PSA doubling;
5. On bone mineral density (sub study in selected centres) and
6. On biochemical markers of bone turnover (sub study in selected centers only).
|- Trial web site||http://www.uroweb.org/research/projects/|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Drs. Christien Caris|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. M. Wirth|
|- Sponsor/Initiator ||European Association of Urology|
(Source(s) of Monetary or Material Support)
|- Brief summary||Zoledronic acid (ZometaŽ) is a third-generation nitrogen-containing bisphosphonate which has been approved in Europe and the US for the treatment of bone metastases (4mg Zoledronic acid iv/month) in a broad range of tumors 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 antitumor effect by bisphosphonates are
The inhibition of osteoclastic bone resorption prevents the release of tumor-promoting growth factors from the bone matrix;
Inhibition of the adhesion of tumor cells to bone matrix;
Inducing tumor cell apoptosis
It is expected that in the present study ZometaŽ in addition to the prevention of bone metastases will show its potential in preventing hormone therapy induced bone loss.
|- Main changes (audit trail)|
|- RECORD||12-sep-2005 - 11-aug-2012|