E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study investigates first line experimental non-surgical therapy in patients with glioblastoma multiforme in good performance status |
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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 determine the efficacy and feasibility of two different chemotherapy regimens alone and when combined with cerebral radiotherapy as first line therapy in patients with newly diagnosed GBM following primary surgery. |
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E.2.2 | Secondary objectives of the trial |
To determine safety of each of these chemotherapy regimens alone and in combination with cerebral radiotherapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Signed informed consent · Histological verified primary glioblastoma multiforme · No prior therapy for GBM, except for primary surgical resection or biopsy · PS 0-2 · Age > 18 · Expected survival > 3 months · Adequate liver, renal and bone-marrow function, determined as: o Thrombocytes > 100 x 109/liter o Hemoglobin >6.2 mmol/liter o Leukocytes > 3 x 109/liter o Neutrophil granulocytes > 1.5 x 109/liter o ASAT and/or ALAT < 3 x upper normal limit o Bilirubin < 1.5 x upper normal limit o Serum-creatinin < upper normal limit or glomerular filtration rate >60 ml/min (corrected for age) determined by measurement of clearance of Cr-EDTA o APTT < upper normal limit o INR < upper normal limit · Fertile women of childbearing age must use proper anti-conception (oral contraceptives, IUD and/or condom). Fertile men must use condom · No sign of cerebral bleeding on cerebral MR-scanning at baseline |
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E.4 | Principal exclusion criteria |
· Previous therapy of GBM, including radiotherapy and the use of biological “ targeted” drug, e.g. drugs targeted against the VEGF- or EGFR pathway · Concurrent use of medication that can affect the interpretation of the results from the study, e.g. use of immunosuppressive drugs, except corticosteroids · Conditions (medical, social or physical) that may compromise proper information and/or follow-up · Other concurrent or previous cancer within 5 years, except adequately treated basal or planocellular skin cancer, or cervical carcinoma in situ · Significant heart disease (according to the New York Heart Association class II or more severe), clinically significant arrhythmia or unstable angina pectoris/acute myocardial infarction within last 6 months · Clinical significant peripheral arterial disease · Known or suspected disorders of coagulation or concurrent therapy with ASA, NSAID or clopidogrel · Major surgery, open biopsy or greater trauma, or expectations thereof, within 28 days prior to start of therapy · Minor surgery or needle biopsy, or expectations thereof, within 7 days prior to start of therapy · Known or suspected abdominal fistulas, gastrointestinal perforations or intra-abdominal abscesses within 6 months prior to start of therapy · Known or active HIV or Hepatitis B/C infection · Concurrent ongoing significant infection or diabetes mellitus not adequately controlled medically · Clinically significant non-healing ulcers · Active ventricular or duodenal ulcers within 6 months prior to start of therapy · Recent bone-fracture (<3 months) · Pregnancy or lactation · Need for systemic anticoagulant therapy at time of start of therapy · Blood pressure > 150/100 mmHg (patients are allowed to receive proper antihypertensive medication) · Proteinuria ≥ 1 gram/day · Known allergy towards irinotecan (or related substance) or vehicle · Known allergy towards temozolomide (or related substance) or vehicle · Known allergy towards bevacizumab (or related substance) or vehicle
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is to determine the response rate. Response is evaluated after 2 cycles of systemic therapy alone, 2 months after completed radiotherapy, and hereafter after every 2nd treatment cycle as long as therapy is continued. |
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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) | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |