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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018337 |
E.1.2 | Term | Glioblastoma multiforme |
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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 whether concurrent radiotherapy with daily temozolomide chemotherapy improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma
- to assess whether adjuvant temozolomide chemotherapy improves survival as compared to no adjuvant temozolomide chemotherapy in patients with non-1p/19q deleted anasplastic glioma |
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E.2.2 | Secondary objectives of the trial |
- to assess whether concurrent and adjuvant temozolomide treatment prolongs progression free survival and neurological deterioration free survival in patients with non-1p/19q deleted anaplastic glioma
- to assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.
- to assess patients with non-1p/19q deleted anaplastic glioma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The combination of : • Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic oligoastrocytoma or anaplastic astrocytoma by local diagnosis AND • Absence of combined 1p/19q loss both of which must have been determined by either local testing or central review • Availability of tumor material for central 1p/19q assessment, central MGMT promoter methylation assessment and central pathology review • WHO performance status 0-2 • Age ≥ 18 years • Previous surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression • Start of radiotherapy within 8 days from randomization • Start of radiotherapy within 7 weeks (49 days) from surgery • Patients must be on a stable or decreasing dose of steroids for at least two weeks • No prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel®) • No prior radiotherapy to the brain • No concomitant treatment with other anti-cancer agents or with any other experimental agent • Adequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days prior to randomization): • neutrophils greater or equal to 1.5*109 cells/l • platelets greater or equal to 100*109 cells/l • bilirubin < 1.5 times upper limit of laboratory normal • alkaline phosphatase, ASAT and ALAT <2.5 times upper limit of laboratory normal • serum creatinine lower than 1.5 times upper limit of laboratory normal • All patients must use effective contraception if of reproductive potential. Females must not be pregnant or breast feeding • Absence of known HIV infection, chronic hepatitis B or hepatitis C infection • Absence of any other serious medical condition that could interfere with follow-up • Absence of any medical condition which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction) • Absence of previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in situ of te cervix and non-melanoma skin cancer. • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. • Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Patients can only be randomized in this trial once.
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is overall survival, as measured from the day of randomization. |
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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 | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 the study occurs when all of the following criteria have been satisfied:
1) thirty days after all patients have stopped protocol treatment 2) the trial is mature for the analysis of the primary endpoint as defined in the protocol 3) 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 | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 6 |