E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hormone refractory metastatic prostate cancer
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E.1.1.1 | Medical condition in easily understood language |
prostate cancer, metastatic, hormones are no further effective |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Proportion of patients with decreased CTCs at 12 weeks after first infusion of zoledronic acid |
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E.2.2 | Secondary objectives of the trial |
•Relationship between PSA and course of CTCs
•Proportion of patients with stable or decreased CTCs at 12 weeks
•Proportion of patients with stable CTCs at 12 weeks
•Analysis of patients based on baseline CTCs (Proportion of patients with stable or decreased CTCs at 12 weeks in a subgroup of patients with >5 CTCs at baseline vs proportion of patients with stable or decreased CTCs below 5 CTCs at baseline)
•Analysis of patients based on baseline CTCs (Proportion of patients with decreased CTCs at 12 weeks in a subgroup of patients with >5 CTCs at baseline vs proportion of patients with decreased CTCs below 5 CTCs at baseline)
•Time until decrease of CTCs
•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 castration resistant prostate cancer (>2 consecutive rising PSA values determined in an > 2 week interval).
No changes in antitumoral treatment planned through the course of study.
Patients with presence of CTCs
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 30 ml/min
Life expectancy 6 months
Signed informed consent prior to trial entry
Prior surgery, chemotherapy and radiotherapy of metastases (including therapeutic radioisotopes such as strontium 89) is allowed. At least 2 months must have elapsed after completion of surgery, chemotherapy and radiotherapy.
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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
Prior treatment with antiresorptive agent (e.g. RANK ligand inhibitor)
Abnormal renal function
Patients with proven 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)
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 12.0 mg/dl (3.00 mmol/L)
Known history or present abuse of alcohol or drugs
Prior malignancy except basal cell or squamous cell skin cancer or any other cancer from which the patient has been disease-free for 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)
Any change in therapy within the last 2 months (Chemotherapy, change in hormonal therapy)
Change of treatment during study duration
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with decreased CTCs at 12 weeks after first infusion of zoledronic acid |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Relationship between PSA and course of CTCs
•Proportion of patients with stable or decreased CTCs at 12 weeks
•Proportion of patients with stable CTCs at 12 weeks
•Analysis of patients based on baseline CTCs (Proportion of patients with stable or decreased CTCs at 12 weeks in a subgroup of patients with >5 CTCs at baseline vs proportion of patients with stable or decreased CTCs below 5 CTCs at baseline)
•Analysis of patients based on baseline CTCs (Proportion of patients with decreased CTCs at 12 weeks in a subgroup of patients with >5 CTCs at baseline vs proportion of patients with decreased CTCs below 5 CTCs at baseline)
•Time until decrease of CTCs
•Safety and Tolerability (adverse events (AEs), serious adverse events (SAEs)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
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 | No |
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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not applikable |
entspricht nicht |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |