E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018337 |
E.1.2 | Term | Glioblastoma multiforme |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 the impact of concurrent and adjuvant temozolomide treatment on the quality of life in patients with ono-1p/19q deleted anaplastic glioma. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
AT REGISTRATION :
• Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic oligoastrocytoma or anaplastic astrocytoma by local diagnosis
• 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
• All patients must use effective contraception id 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 can 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 any psychological, familial,sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
RANDOMIZATION:
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 (extra 2 days could be allowed).
•Patients must be on a stable or decreasing dose of steroids for at least two weeks.
•Adequate hematological, renal and hepatic function.
•All patients, must use effective contreception 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.
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E.4 | Principal exclusion criteria |
•Privious other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to registration; and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix.
•Prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel®)
• Prior radiotherapy to the brain
RANDOMIZATION:
• Prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel®).
• Prior radiotherapy to the brain. |
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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.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints of the study are progression free survival, neurological deterioration free survival, quality of life, toxicity, and development of cognitive deterioration. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression free survival: Median 3, 4 and 5 years
Neurological deterioration free survival: Median 3, 4 and 5 years
Quality of life (QOL):
•Overall comparison of OL scores up to Progression Disease.
•Comparison at 4 weedks of Radiotherapy (RT) and every 3 monthly visit up to progression disease.
Toxicity: worst grade:
•During RT or concomitant Temozolomide (TMZ)/RT
•During adjuvant TMZ
•Follow-up period
Mini mental status examination: median time till cognitive deterioration |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | No |
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 |
Canada |
Australia |
Israel |
Switzerland |
Turkey |
United States |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |