| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Elderly (>65 years of age) patients with newly diagnosed, and histopathologically confirmed, glioblastoma multiforme (GBM, WHO grade IV) , who have had prior surgery/biopsy at diagnosis and who are not deemed suitable by their treating physician to receive the standard radiotherapy regimen (60 Gy / 30 fractions over 6 weeks) in combination with temozolomide. |
|
| 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 |
|
| 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 compare the overall survival (OS) rates between short-course radiation therapy alone and shortcourse radiation therapy given together with concurrent and adjuvant temozolomide, in elderly (>65 years of age) patients with newly diagnosed glioblastoma multiforme (GBM, WHO grade IV) , who have had prior surgery/biopsy at diagnosis and who are not deemed suitable by their treating physician to receive the standard radiotherapy regimen (60Gy/30 fractions over 6 weeks) in combination with temozolomide. |
|
| E.2.2 | Secondary objectives of the trial |
To compare progression-free survival (PFS) between the two arms.
To compare the nature, severity, and frequency of adverse events between the two arms.
To compare the quality of life between the two arms using the EORTC QLQ-C30 and the EORTC Brain Cancer Module (QLQ-BN20).
To conduct molecular correlative studies, as follows: − Mandatory
- To collect tumour samples obtained at the time of disease diagnosis in order to determine the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter.
− Optional - To bank tumour samples obtained at the time of disease diagnosis for future studies aiming to correlate outcomes and response to treatment to the expression levels or genetic alterations at diagnosis of other scientifically justified markers, as considered appropriate. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients must fulfill all of the following criteria to be eligible for admission to the study:
1. Histopathologically confirmed newly diagnosed glioblastoma multiforme (GBM, WHO grade IV). The histological diagnosis must have been made after biopsy or neurosurgical tumour resection.
2. Initial surgery/biopsy at diagnosis performed < 4 weeks (28 days) prior to randomization.
3. Patient’s age is > 65 years.
4. Patient is not deemed suitable by the treating physician to receive the standard radiotherapy regimen (60 Gy / 30 fractions over 6 weeks) in combination with temozolomide.
5. ECOG performance status of 0, 1 or 2.
6. Patient may have received and continue to receive corticosteroids, but s/he have to be on a stable or decreasing dose for at least 14 days prior to randomisation.
7. Patient has not received prior chemotherapy or radiotherapy.
8. Adequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to randomisation: - Absolute granulocyte count (AGC) &#8805; 1.5 x 109/L (1,500 cells/mm3) - Platelet count &#8805; 100 x 109/L (100,000 cells/mm3) - Serum creatinine &#8804; 1.5 times the upper limit of normal - Total serum bilirubin &#8804; 1.5 times the upper limit of normal - ALT (SGPT) < 2.5 times the upper limit of normal - and/or AST (SGOT) < 2.5 times the upper limit of normal
9. Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French or any other official language into which the questionnaire is required to be translated. The baseline assessment must have already been completed. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.
10. Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. A copy of the initial full board REB approval and approved consent form must be sent to the central office. The patient must sign the consent form prior to randomisation.
11. Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomised on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
12. All other investigations (physical examination, biochemistry and hematology tests etc.) as listed in section 6.0 of the protocol have been performed prior to randomisation (with the exception of requests for diagnostic tissue blocks / slides to be used for central pathology review and correlative studies which will be done after randomisation).
13. Protocol treatment is to begin within 2 weeks of patient randomisation. |
|
| E.4 | Principal exclusion criteria |
| Patients who fulfill any of the following criteria are not eligible for admission to the study: 1. Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for &#8805; 5 years. 2. Patients with a serious active infection (such as a wound infection requiring parenteral antibiotics) at the time of randomisation or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment. 3. Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol. 4. Patients with known hypersensitivity to temozolomide or compounds with similar chemical composition to temozolomide. 5. Patients who have had treatment with any investigational cancer drug prior to randomisation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is the overall survival (OS), which is defined as the time from randomisation to the time of death from any cause. |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Quality of life assessment; tissue collection for MGMT promoter methylation testing, and for banking |
|
| 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) | 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 | 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 |
| Short-course radiotherapy only |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| 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 |
|
| 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
|
| 1. 30 days after all (randomised) patients have completed their treatment and 2. Trial is mature for analysis of the primary endpoint as per protocol and 3. Database is fully cleaned & frozen for the analysis. |
|
| 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 | 0 |
| 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 | 0 |
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