Clinical trial NCT00294437: ZOMETA® (Zoledronic Acid) for Prevention of Bone Metastases
Official title: Randomised Open-label Multicenter Prosp. Clinical Study to Show the Efficacy of IV ZOMETA® 4mg for Prevention of Bone Metastases in Hormone-naïve High Risk Patients With Locally Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Zometa
Lead sponsor: Central European Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2006-02-22
Enrollment: 376
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: To determine if therapy with Zometa® (zoledronic acid) 4mg will be effective in preventing the occurrence of bone metastases in prostate cancer patients at high risk of developing them. In addition, pain and analgesic scores and overall safety are to be evaluated throughout the study.

Detailed description: This is a prospective, randomized, stratified open-label (Zometa + hormonal ablation versus hormonal ablation alone) multicenter clinical study evaluating the efficacy of Zometa 4mg given every 3 month as an adjunct to hormonal or surgical castration for prevention of bone metastases in locally advanced, high risk prostate cancer patients, who are hormone-naiv at time of randomization. the primary efficacy variable is the time to occurrence of first bone metastases.

Zometa® (zoledronic acid) provided as 4mg lyophilised powder Supplementation 500mg Calcium +400-500IU Vitamin D p.o. qd

Arm A:

Zometa® (zoledronic acid) in 100ml of calcium free solution i.v. as a 15 minute infusion every 3 months

Arm B:

no reference therapy

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Age \> 18 years
* Histologically confirmed diagnosis of carcinoma of the prostate
* ECOG performance status of 0, 1, or 2
* No radiological evident bone metastasis (negative bone scan or verification of suspected foci as benign lesions by additional radiological examination)
* T3-4 AND highest pre-study PSA \>20 ng/ml AND Gleason score = 8 (or Gleason grade = 4)
* Patients with prior prostatectomy or prior local radiotherapy are eligible for this study
* Patients are destined to receive medical (LHRH analogue) or surgical (orchiectomy) castration and Zometa® treatment will start not later than 6 weeks after surgery
* Patients should be fully recovered from prior interventions where applicable

Exclusion Criteria:

* Patients with a serum creatinine determination \>265 µmol/L (3.0 mg/dL)
* Patients that received prior medical (LHRH analogue) castration
* Current (or previous) evidence of metastatic disease to the bone
* History of any other neoplasm within the past five years except for nonmelanomatous skin cancer.
* Previous hormonal therapy with LHRH agonists or other forms of hormonal ablation
* WBC\<3.0x109, ANC \< 1500/mm3, Hgb\<8.0 g/dL, platelets \< 75 x 109/L
* Liver function tests \>2.5 ULN
* Prior treatment with Zometa® (zoledronic acid) or other bisphosphonates
* Treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to the date of randomization (Visit 2)
* Use of other investigational drugs (drugs not marketed for any indication) within 30 days prior to the date of randomization (Visit 2)
* Patients with evidence in the six months prior to randomization of severe cardiovascular disease (defined as uncontrolled congestive heart failure), hypertension refractory to treatment, or symptomatic coronary artery disease uncontrolled by treatment
* History of noncompliance to medical regimens and patients who are considered potentially unreliable or incapable of giving informed consent as judged by the investigator.

Primary outcomes:
measure: Time to occurrence of first bone metastasis, as assessed by bone scan and confirmed by additional radiological examination
Secondary outcomes:
measure: To assess the effects of i.v. Zometa® (zoledronic acid) 4 mg, with respect to the following efficacy parameters as well as safety and tolerability:
measure: Effects on pain and analgesic drug consumption, assessed by the composite pain score from BPI (Brief Pain Inventory) for pain and by analgesic score
measure: Time to first event of bone pain
measure: Time to first occurrence of Skeletal Related Events (SREs), defined as pathologic bone fractures, spinal cord compression, surgery to bone, radiation therapy to bone (including the use of radioisotopes)
measure: Proportion of patients in each arm having SRE
measure: Serum PSA
measure: Overall safety
Other outcomes:
Locations:
city: Leoben
country: Austria
facility: LKH Leoben, Abt. für Innere Medizin
state: Steiermark
city: Baden bei Wien
country: Austria
facility: Thermenkh Baden, Urologie
city: Graz
country: Austria
facility: LKH Graz Univ. Klinik f Urologie
city: Innsbruck
country: Austria
facility: LKH Innsbruck, Dept f. Urologie
city: Linz
country: Austria
facility: KH d Elisabethinen Linz, Dep of Urology
city: Linz
country: Austria
facility: KH der Barmherzigen Schwestern, Dept Urologie
city: Salzburg
country: Austria
facility: LKH Salzburg, Clinic f Radiotherapy a Radiooncology
city: Sarajevo
country: Bosnia and Herzegovina
facility: Institute for Oncology
city: Plovdiv
country: Bulgaria
facility: Plovdiv Cancer Center
city: Sofia
country: Bulgaria
facility: SBALO National Oncology Center
city: Sofia
country: Bulgaria
facility: SBALO National Oncology Center
city: Sofia
country: Bulgaria
facility: Sofia Cancer Center compl. Mladost ,
city: Stara Zagora
country: Bulgaria
facility: MODOSZ Oncology Dispensary
city: Tarnovo
country: Bulgaria
facility: Modozs-Veliko
city: Varna
country: Bulgaria
facility: Oncological Hospital
city: Split
country: Croatia
facility: Univ. Hospital, Dep of Pathophysiology
city: Varazdin
country: Croatia
facility: GH, Dep Oncology and Reumatology
city: Zagreb
country: Croatia
facility: Clinical Hospital
city: Brno
country: Czech Republic
facility: FH, Urological Clinic
city: Kromeriz
country: Czech Republic
facility: Hospital Kromeriz, Dep of Urology
city: Prague
country: Czech Republic
facility: FN Motol, Dep of Urology
city: Usti Nad Labem
country: Czech Republic
facility: Centre of Oncology
city: Tallinn
country: Estonia
facility: Mustamae Korpus
city: Tartu
country: Estonia
facility: Clinic of surgery
city: Budapest
country: Hungary
facility: Dept. Of Urology , Jahn Ferenc Delpesti Hospital
city: Budapest
country: Hungary
facility: karolyi sandor Hospital, Dept of Urology
city: Budapest
country: Hungary
facility: Semmelweiss Univ of Medicine, Clinic of Urology
city: Pecs
country: Hungary
facility: Univ. of Pecs,Urologic Clinic
city: Szombathely
country: Hungary
facility: Dept. Of Urology and Surgery
city: Vilnius
country: Lithuania
facility: Lithuanian Oncology Center
city: Podgorica
country: Montenegro
facility: Clinical Center of Montenegro
city: Krakow
country: Poland
facility: Centrum Onkologii Instytut
city: Szczecin
country: Poland
facility: Medical Academy
city: Warsaw
country: Poland
facility: Central Rail Hospital,
city: Warsaw
country: Poland
facility: Medical Academy
city: Brasov
country: Romania
facility: P.D.R. Clinic
city: Bucharest
country: Romania
facility: Fundeni Hospital, Dep of Urology
city: Bucharest
country: Romania
facility: Saint John Emergency Clinical Hospital
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic Cluj
city: Craiova
country: Romania
facility: Emergency Clinical County Hospital , Clin Oncol. Dep
city: Iasi
country: Romania
facility: University Hospital
city: Moscow
country: Russian Federation
facility: Hertzen Research Oncological Institute
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Oncology Institute Belgrade
city: Belgrade
country: Serbia
facility: Oncology Institute
city: Nis
country: Serbia
facility: Clinical Center
city: Sremska Kamenica
country: Serbia
facility: Institute for Oncology
city: Bratislava
country: Slovakia
facility: FNsP - akad L. Derea Urology
city: Kosice
country: Slovakia
facility: FNsP Dep of Urology
city: Martin
country: Slovakia
facility: FN sP Dep of Urology
city: Ljubljana
country: Slovenia
facility: University Clinical Center
city: Maribor
country: Slovenia
facility: Gh, Dep of Urology
city: Claremont
country: South Africa
facility: Turret House
city: Johannesburg
country: South Africa
facility: Johannesburg Hospital Dep of Urology
city: Pietermaritzburg
country: South Africa
facility: St. Annes Hospital
city: Pretoria
country: South Africa
facility: Urological Hospital
Study officials:
affiliation: Univ. Klinik für Urologie
name: Bobak Djavan, Prof
role: PRINCIPAL_INVESTIGATOR
References: