ZOMETA® (Zoledronic Acid) for Prevention of Bone Metastases

Condition(s) targeted: Prostate Cancer

Intervention: Zometa (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Central European Cooperative Oncology Group

Official(s) and/or principal investigator(s):
Bobak Djavan, Prof, Principal Investigator, Affiliation: Univ. Klinik für Urologie

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.

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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Time to occurrence of first bone metastasis, as assessed by bone scan and confirmed by additional radiological examination

Secondary outcome:

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:

Effects on pain and analgesic drug consumption, assessed by the composite pain score from BPI (Brief Pain Inventory) for pain and by analgesic score

Time to first event of bone pain

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)

Proportion of patients in each arm having SRE

Serum PSA

Overall safety

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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.

LKH Graz Univ. Klinik f Urologie, Graz, Austria

KH der Barmherzigen Schwestern, Dept Urologie, Linz, Austria

LKH Innsbruck, Dept f. Urologie, Innsbruck, Austria

Thermenkh Baden, Urologie, Baden bei Wien, Austria

LKH Salzburg, Clinic f Radiotherapy a Radiooncology, Salzburg, Austria

KH d Elisabethinen Linz, Dep of Urology, Linz, Austria

Institute for Oncology, Sarajevo, Bosnia and Herzegovina

Plovdiv Cancer Center, Plovdiv 4000, Bulgaria

SBALO National Oncology Center, Sofia 1527, Bulgaria

Sofia Cancer Center compl. Mladost ,, Sofia, Bulgaria

SBALO National Oncology Center, Sofia, Bulgaria

Modozs-Veliko, Tarnovo, Bulgaria

MODOSZ Oncology Dispensary, Stara Zagora, Bulgaria

Oncological Hospital, Varna, Bulgaria

Clinical Hospital, Zagreb, Croatia

Univ. Hospital, Dep of Pathophysiology, Split, Croatia

GH, Dep Oncology and Reumatology, Varazdin, Croatia

FN Motol, Dep of Urology, Prague, Czech Republic

Centre of Oncology, Usti Nad Labem, Czech Republic

FH, Urological Clinic, Brno, Czech Republic

Hospital Kromeriz, Dep of Urology, Kromeriz, Czech Republic

Mustamae Korpus, Tallinn, Estonia

Clinic of surgery, Tartu, Estonia

Univ. of Pecs,Urologic Clinic, Pecs, Hungary

Semmelweiss Univ of Medicine, Clinic of Urology, Budapest, Hungary

Dept. Of Urology and Surgery, Szombathely, Hungary

Dept. Of Urology , Jahn Ferenc Delpesti Hospital, Budapest, Hungary

karolyi sandor Hospital, Dept of Urology, Budapest, Hungary

Lithuanian Oncology Center, Vilnius, Lithuania

Medical Academy, Warsaw, Poland

Central Rail Hospital,, Warsaw, Poland

Medical Academy, Szczecin, Poland

Centrum Onkologii Instytut, Krakow, Poland

Emergency Clinical County Hospital , Clin Oncol. Dep, Craiova, Romania

Institutul Oncologic Cluj, Cluj-Napoca 400015, Romania

Saint John Emergency Clinical Hospital, Bucharest, Romania

Fundeni Hospital, Dep of Urology, Bucharest, Romania

University Hospital, Iasi, Romania

P.D.R. Clinic, Brasov, Romania

Medical Radiological Research Center, Obninsk, Russian Federation

Hertzen Research Oncological Institute, Moscow, Russian Federation

Oncology Institute, Belgrade, Serbia and Montenegro

Institute for Oncology, Sremska Kamenica, Serbia and Montenegro

Clinical Center, Nis, Serbia and Montenegro

Clinical Center of Serbia, Belgrade, Serbia and Montenegro

Clinical Center of Montenegro, Podgorica, Serbia and Montenegro

Oncology Institute Belgrade, Belgrade, Serbia and Montenegro

FNsP - akad L. Derea Urology, Bratislava, Slovakia

FN sP Dep of Urology, Martin, Slovakia

FNsP Dep of Urology, Kosice, Slovakia

Gh, Dep of Urology, Maribor, Slovenia

University Clinical Center, Ljubljana, Slovenia

Turret House, Claremont, South Africa

Urological Hospital, Pretoria, South Africa

Johannesburg Hospital Dep of Urology, Johannesburg, South Africa

St. Annes Hospital, Pietermaritzburg, South Africa

LKH Leoben, Abt. für Innere Medizin, Leoben, Steiermark 8700, Austria

Starting date: December 2003
Last updated: May 10, 2007