E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glioblastoma, recurrent/progressive |
Glioblastom med vækst/tilbagefald efter primær behandling |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent malignant brain tumor |
Ondartet hjernesvulst med tilbagefald efter primær behandling |
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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 |
The aim of this study is to make preliminary assessment of PD-L1 and other immune related biomarkers that might act as predictors of anti-tumor activity of Nivolumab. |
Formålet med dette forsøg er at undersøge effekten behandling med nivolumab i kombination med bevacizumab og sammenligne dette med immunsystemets og kræftcellers reaktion på behandlingen ved at undersøge tumorvæv. |
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E.2.2 | Secondary objectives of the trial |
•Assessment of the safety and tolerability of Nivolumab in combination with Bevacizumab for patients with current GBM.
•To asses Progression-Free Survival (PFS) in treatment Arm A and Overall Response Rate (ORR), Duration of response (DOR) and Overall survival (OS) in treatment Arm B
•Investigate the predictive ability of FET PET/MRI on response assessment with regard to PFS and OS.
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Deridover ønskes at evaluere sikkerheden og effekten af Nivolumab og Bevacizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Pathologically confirmed GBM (including all histologic variants);
2.Age ≥ 18 years;
3.Evidence of radiological (MRI-scan) measurable recurrent progressive GBM evaluated by the Response Assessment in Neuro-Oncology [RANO] criteria;
4.Measurable disease according to the RANO guidelines, within 14 days of starting treatment. Measurable disease after surgery on arm A is not required with radiographic evidence of recurrent disease after treatment with temozolomide and radiotherapy;
5.An interval of at least 4 weeks between prior radiotherapy or chemotherapy and enrolment on this protocol;
6.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2;
7.Life expectancy, in the opinion of the investigator > 3 month;
8.Written informed consent obtained prior to any screening procedures. Patients must be willing and able to comply with the protocol and aware of the investigational nature of this study; |
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E.4 | Principal exclusion criteria |
1.Patients must not have significant medical illness that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy;
2.Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids (equivalent to max dose of 20 mg prednisolone per day) and stable for at least 5 days prior to day 1;
3.Any condition (medical, social, psychological), which would prevent adequate information and follow-up;
4.Any other active malignancy or previous malignancies within the last 5 years, except, adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ;
22.History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegner´s granulomatosis, Sjögren´s syndrome, Bell´s palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis;
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E.5 End points |
E.5.1 | Primary end point(s) |
•The primary objective ist o make preliminary assessment of PD-L1 and other immune related biomarkers that might acta s predictors of antitumor activity of nivolumab |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The biomarklers analyses will be sampled during the first Weeks of therapy and at every evaluation. |
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E.5.2 | Secondary end point(s) |
• 6-months Progression-free survival (6mPFS) rate (Progression of disease defined according to the iRANO criteria)
• Response rate according to the iRANO criteria
• Median progression-free survival (mPFS)
• Median overall survival (OS)
• Safety
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will undergo physical and neurological examination every 4 weeks and MRI at baseline and MRI every 8 weeks.
FET-PET MRI and perfusion CT will be performed at baseline and after 8-10 weeks.
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 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 | 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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |