E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Phase II study of ZK 219477 in patients with recurrent glioblastoma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
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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 |
The principal objective of the trial is to assess the therapeutic activity of ZK 219477 in patients with recurrent GBM. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are the documentation of the safety profile, the mechanism of action and the pharmacokinetic of ZK 219477. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with histologically proven glioblastoma (according to the WHO classification ; the presence of oligodendroglial elements is allowed provided these make up less than 25% of the tumor). ♦ Recurrent disease documented by MRI after failing prior therapy (usually standard RT with concomitant and maintenance temozolomide ). ♦ Patients with multifocal disease not amenable to radiotherapy are eligible, provided they have received no or no more than 1 line of prior chemotherapy. ♦ Presence of at least one bidimensionally measurable target lesion (contrast enhancing lesion) with a largest diameter of at least 2cm, based on MRI scan done within two weeks prior to registration. ♦ No prior chemotherapy for recurrent disease, or a maximum of only one prior chemotherapy regimen given as adjuvant treatment. In all cases, prior chemotherapy must be completed for at least 4 weeks (or 6 weeks if a nitrosoureas contain regimen was used) prior to registration on study. ♦ Patients who received concomitant/adjuvant temozolomide as first-line therapy are eligible. ♦ Age ≥ 18 years. ♦ WHO Performance status 0-2. ♦ Patients must be on a stable or decreasing dose of corticosteroids for at least one week prior to inclusion/registration. ♦ No prior surgery for recurrent primary brain tumor within the last 3 months prior to registration, except if immediate (within 72 hours) post operative imaging is available documenting clearly measurable residual disease or a postoperative follow up gives evidence of a progressive and measurable target lesion, or a second measurable target lesion outside the surgical area is present. ♦ Completion of prior radiotherapy to the brain for more than 3 months prior to registration. ♦ No prior treatment with high dose radiotherapy (> 65 Gy), stereotactic radiosurgery or internal radiation therapy unless the recurrence is subsequently histologically confirmed. ♦ Patients must not be taking antiepileptic agents or be on nonenzyme inducing antiepileptic drugs (EIAED). Patients taking phenytoin, carbamazepin or phenobarbital are not eligible. ♦ For patients on EIAED, they should have been switched to non-EIAEDs with a wash-out period of at least one month. ♦ Normal hematological functions: neutrophils ≥ 1.5 x 109 cells/l, platelets ≥100 x 109 cells/l ♦ Normal liver function: bilirubin < 1.5 x ULN, alkaline phosphatase and transaminases (ASATALAT) < 2.5 times the upper limit of the normal range. ♦ Serum creatinine < 1.5 x ULN. ♦ Clinically normal cardiac function without history of ischemic heart disease in the past 12 months. Absence of cardiac insufficiency NYHA grade III and IV, instable angina, arrhythmia. Patients with stable ischemic heart disease (e.g. treated prior angina, stable under appropriate therapy) are eligible. ♦ No previous or current malignancy at other sites with the exception of cone biopsied carcinoma of the cervix and adequately treated basal or squamous cell skin carcinoma. ♦ All patients (male and female) must use effective contraception methods according to CPMP/ICH/286/95 if of reproductive potential (e.g. implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner). ♦ Females must not be pregnant at entry or lactating. ♦ Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule There is no reason to believe that the representation would differ in the studied population, therefore no specific stratification is performed to ensure gender distribution. patients are informed on the use of their coded data and if the patient refuses to have his data used, he/she cannot sign the informed consent and cannot be included in the study. |
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
The principal end-point is treatment success. Secondary endpoints are the objective response as defined by the McDonald’s criteria, duration of response and progression-free survival and overall survival at 6 and 12 months. All patients will be followed until death. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of study occurs when all of the following criteria have been satisfied: 1. The trial is mature for the analysis of the primary endpoint as defined in the protocol 2. The database has been fully cleaned and frozen for this analysis |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |