E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent Glioblastoma multiforme |
Tilbagevendende Glioblastoma multiforme |
|
E.1.1.1 | Medical condition in easily understood language |
Recurrent brain tumor |
Tilbagevendende hjernetumor |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Determine changes in tumor perfusion parameters defined by perfusion MRI and changes in tumor proliferation defined by FLT- and FET-PET |
Bestemme ændringer i tumor proliferation med FET- og FLT-PET og vaskulære ændringer med perfusion MRI før og efter behandling med bevacizumab monoterapi |
|
E.2.2 | Secondary objectives of the trial |
• Determine changes in tumor and blood biomarkers of angiogenesis, hypoxia and proliferation
• Determine changes in tumor and blood biomarkers of angiogenesis, hypoxia and proliferation and correlate these with clinical outcome.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent
• Histological verification of glioblastoma multiforme with progression after temozolomid and radiotherapy
• Evidence of measurable recurrent progressive disease (MRI scan)
• Clinical (RANO/MacDonald criteria) or CT/MRI scan verified progression
• An interval of at least 4 weeks between prior surgical resection and study enrolment
• An interval of at least 4 weeks between prior radiotherapy or chemotherapy and enrolment on this protocol.
• WHO performance status 0-1
• Age > 18
• Life expectancy > 3 month
• Normal organ function:
• Platelets > 125 x 109/l
• Haemoglobin > 6,2 mmol/l
• Leukocytes > 3 x 109/l
• ACN> 1,5 x 109/l
• ASAT or ALAT < 3 x upper normal limit
• Bilirubin < 1,5 x upper normal limit
• Creatinine within normal limits
• APTT < normal limit
• INR < normal limit
• Fertile females must use oral contraceptive, IUD (intrauterine device), gestagen sustained release injection, subdermal implantation, transdermal patch or hormonal vaginal ring. This must continue at least three months after the patients is off-study. Fertile males must use preservatives
• No sign of cerebral bleeding |
|
E.4 | Principal exclusion criteria |
• Radiotherapy or chemotherapy within the last 4 weeks.
• Prior treatment with bevacizumab or another VEGF inhibitor
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
• Any condition (medical, social, psychological), which would prevent adequate information and follow-up
• Any significant cardiac disease (New York Heart Association Class II or greater), arytmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris.
• Clinically significant peripheral vascular disease
• Evidence of bleeding diathesis or coagulapathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the curse of the study
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to day 0
• History of known HIV, Hepatitis B and Hepatitis C negative
• Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound, ulcer or bone fracture
• Pregnancy or breast feeding
• Requires therapeutic anti-coagulation (except LMWH or heparin flushing of central venous catheters) or anti-thrombotic therapy (except acetyl salicylic acid < 325 mg daily and clopidogrel)
• Blood pressure > 150/100 mm Hg
• Grade 2 or greater proteinuria |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Changes in tumor perfusion parameters defined by perfusion MRI and changes in tumor proliferation defined by FLT- and FET-PET and correlate these with the clinical outcome |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and within the first two weeks after administartion of study drug |
|
E.5.2 | Secondary end point(s) |
Changes in tumor and blood biomarkers of angiogenesis, hypoxia and proliferation and
changes in tumor and blood biomarkers of angiogenesis, hypoxia and proliferation and correlate these with clinical outcome.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and within the first two weeks after administartion of study drug |
|
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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
|
last visit of the last subject undergoing the trial |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |