E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with prostate or breast cancer with bone metastasis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036910 |
E.1.2 | Term | Prostate cancer NOS |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess course of bone turn-over markers (PINP, bALP, ICTP and CTX) |
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E.2.2 | Secondary objectives of the trial |
- Relationship between tumour burden/metastatic sites assessed by bone scan Soloway Score (63)) and level of bone markers at study entry - Pain assessment (VAS) and analgesics score - Relationship between Pain and course of bone turn-over markers - Rate of SREs - Relationship between SREs and bone turnover markers - Quality of life questionnaire (EORTC 30) - Course of PSA (Patients with prostate cancer only) - Course of urinary NTX ( in centers where storage at -20°C is possible) - Safety and Tolerability (adverse events (AEs), serious adverse events (SAEs))
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically proven carcinoma of the prostate with evidence of at least one cancer related bone lesion with or without hormonal treatment. - Histologically proven carcinoma of the breast with evidence of at least one cancer related bone lesion - Negative pregnancy test at screening in case of child-bearing potential. - Performance status ECOG 0-2 - Laboratory requirements: a) hepatic function: total bilirubin ≤ 2,5 times the upper- normal limit of the institution, SGPT, SGOT ≤ 2,5 times the upper-normal limit of the institution. - Renal function: creatinine clearance more or equal 30 ml/min - Normal cardiac function - Life expectancy more or equal 6 months - Signed informed consent prior to trial entry - Patients of more or equal 18 years - Patients must be accessible for treatment - Standardized therapy for pre- und postmenopausal women is allowed - Prior surgery, chemotherapy and radiotherapy is allowed. At least 4 weeks must have elapsed since the completion of surgery, chemotherapy and radiotherapy to breast or bone. |
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E.4 | Principal exclusion criteria |
- Prior treatment with bisphosphonates within 6 months before study start, and during treatment with zoledronic acid - No presence of at least one cancer-related bone lesion that is detectable on conventional radiographs of bone or detectable on a bone scan and confirmed by MRT or CT at screening - Abnormal renal function as evidenced by A calculated creatinine clearance < 30 ml/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula:
CrCl = [[140-age (years)] x weight (kg)] / [72 x serum creatinine (mg/dL)] {x 0.85 for female patients}
- Patients with clinically symptomatic brain metastases - History of diseases with influence on bone metabolism such as Paget´s disease and primary hyperparathyroidism and with need of treatment for osteoporosis (defined according to DVO, T-Score ≤2.5). - Severe physical or psychological concomitant diseases that expected to impair compliance with the provisions of the study protocol or impair the assessment of drug of patient safety (clinically significant ascites, NYHA III or IV, cardiac failure, clinically relevant pathologic findings in ECG) - Breast feeding or Pregnancy, confirmed by a positive serum hCG laboratory test (> 5 mIU/ml) - Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >25 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy or are using one or more medically acceptable methods of contraception. - Known hypersensitivity to zoledronic acid or other bisphosphonates - Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or more or equal 12.0mg/dl (3.00 mmol/L) - Known history or present abuse of alcohol or drugs - Subjects who, in the opinion of the investigator, are unlikely to cooperate fully during the study - Previous Radiation therapy to bone (including therapeutic radioisotopes such as strontium 89) within 1 month - Prior malignancy except basal cell or squamous cell skin cancer or any other cancer from which the patient has been disease-free for more or equal 5 yrs. - Use of other investigational drugs at the time of enrollment, or within 30 days before enrollment - Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures. - Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of the effect of Zoledronic Acid given every 4 weeks for 4 months on bone metabolism. Assessment will carried out by the course of bone turn-over markers. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |