E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
It is an open-label, randomised multicentric phase II study of prolonged adjuvant Temozolomide versus "stop and go" in glioblastoma patients. This study will include a total of 70 patients. The study will determine the time to progression under TMZ, overall survival,progression-free survival (PFS),quality of life of patients. It will also determine the toxicity,response rate of Temozolomide in rechallenge arm and if the MGMT gene status can predict a benefit of TMZ in terms of PFS. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether prolonged administration of Temozolomide in glioblastoma patients increase their progression-free and overall survival at 6 months.
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E.2.2 | Secondary objectives of the trial |
1) To assess the safety and adverse event profile of prolonged adjuvant Temozolomide by using Common Terminology Criteria for Adverse Events (CTCAE 3.0). 2) To compare the Health-Related Quality of Life of the patients randomized in the two treatment arms by using the EORTC QLQ-C30 questionnaire and to study chages of QoL over time. 3) To measure the overall tumor response in patients when they are rechallenge with Temozolomide in the Stop and Go arm. 4) To measure the time to progression under Temozolomide in the Stop and Go arm. 5) To compare the time to progression under Temozolomide defined as the time between randomization and progression under Temozolomide between the two randomized treatment arms. 6) To determine if MGMT gene methylation status can predict a benefit of Temozolomide treatment in terms of Progression-Free Survival (both arms) and tumor response (only in the Stop and Go arm).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients with histologically confirmed diagnosis of GBM. 2) Availability of pre-treatment GBM tissue to determine the activation status of MGMT gene is not mandatory but strongly recommended 3) Patients must have received radiation and TMZ for 6 weeks followed by 6 months of TMZ. Randomization should be performed within the 6 weeks after the last chemotherapy. 4) A brain MRI with or without a PET-Scan-methionine postive must be performed before enrollment. 5) Age ≥ 18 years 6) Karnofsky Performance status ≥70 7) Normal haematological functions: ANC ≥1.5*109cells/l, platelets ≥100*109 cells/l 8) Normal liver function: total bilirubin < 1.5 x ULN, alkaline phosphatase and transaminases (ASAT/ALAT) <2.5 times the upper limit of the normal range 9) Serum creatinine <1.5 x ULN 10) Clinically normal cardiac function without history of ischaemic heart disease in the past 12 months. Absence of cardiac insufficiency NYHA grade III and IV, instable angina, arrhythmia 11) No active malignancy (except treated basal or squamous cell skin carcinoma). 12) All patients (male and female) with reproductive potential must use effective contraception. Females must have a negative serum pregnancy test at entry to study. 13) Signed informed consent from the patient or legal representative must be obtained
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E.4 | Principal exclusion criteria |
All non inclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Time to progression under TMZ defined as the time between randomisation and progression under Temozolomide. |
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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 | 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 | 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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
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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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |