E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
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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 evaluate safety and efficacy of ZK219477 in the treatment of pre-treated, recurrent GBM patients. An optional PK study will be performed in selected patients. |
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E.2.2 | Secondary objectives of the trial |
Response rates CR PR , Median Survival Time MST . |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Histologically proven at diagnosis GMB - Age 18-70 years - KPS 70 - Life expectancy of at least 3 months - Presence of at least one bi-dimensionally measurable lesion on gadolinium Gd -enhanced MRI, indicating progressive or recurrent disease at least 8 weeks after standard external-beam radiotherapy - Recurrence or progression after treatment with radiotherapy and temozolomide. Also patients with residual disease after surgery for recurrent GBM will be included - Adequate bone marrow reserve leucocytes 3,500/ml, ANC 1,500, platelets 100,000/ml ; normal baseline liver serum bilirubin 20umol/L , renal serum creatinine 150umol/L and cardiac function - Absence of infectious disease, debilitatig chronic diseases, known psychiatric disorders - Corticosteroid dose stable for at least 1 week - Adequate recovery from previous surgery, radiation and chemotherapy - Negative pregnancy test at enrolment in females of chil-bearing potential - Agreement to use effective contraception methods in adults of reproductive potential - Written informed consent |
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E.4 | Principal exclusion criteria |
- Pregnancy - Chemotherapy or radiotherapy within 4 weeks before screening - History of allergic reactions due to compounds of similar chemical or biologic composition to ZK219477 - Uncontrolled intercurrent illness including, but not limited, to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrythmia or psychiatric illness/social situations that would limit compliance with study requirements - HIV infection - Any prior treatment with epothilones, other tubulin-targetting as taxanes e. paclitaxel, docetaxel and vinca alcaloids e.g. vincristine, vinblastine, vinorelbine - Peripheral neuropathy - Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix - Active infection - Breast-feeding - Subjects who have received an experimental drug or have participated in a clinical trial within 3 months prior to screening - Employees of the investigator or study centre with direct involvement in the proposed study or other studies under the direction of thet investigator or study centre |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progession Free Survival at 6 months PFS-6 . Treatment toxicity will be assessed using CTCAE, Version 3.0, except for neurological toxicity that will be assessed also by means of the Scottish Gynaecological Cancer Trial Group SGCTG Neurotoxicity Score and elecromyography. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |