E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
newly diagnosed glioblastoma |
neudiagnostiziertes Glioblastom |
|
E.1.1.1 | Medical condition in easily understood language |
newly diagnosed brain tumor |
neudiagnostizierter Hirntumor |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine whether overall survival of newly diagnosed GBM patients treated with lysate-loaded, mature dendritic cell vaccines as add-on to the standard of care consisting of resection, radiotherapy with concomitant temozolomide chemotherapy and subsequent adjuvant temozolomide chemotherapy is superior to the treatment with the standard of care alone |
Das primäre Studienziel ist zu prüfen, ob die zusätzliche Vakzinierung mit Tumorlysat-beladenen, reifen Dendritischen Zellen das Überleben (Overall Survival, OS) von Patienten mit neudiagnostiziertem Glioblastom verbessert, die mit der gegenwärtigen Standardtherapie aus Radiochemotherapie und adjuvanter Temozolomid-Chemotherapie behandelt werden. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are comparing progression-free survival and 6, 12 and 24 month OS and PFS rates, the safety profile, overall and neurological performance and the quality of life between the two treatment groups |
Sekundäre Studienziele sind die Evaluierung des progressionsfreien Überlebens (Progression-Free Survival, PFS) und der PFS and OS Raten nach 6, 12 und 24 Monaten, des Sicherheitsprofils der Therapie, der Lebensqualität der Patienten sowie ihrer allgemeinen und neurologischen Leistungsfähigkeit. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- newly diagnosed, monofocal GBM, IDH wildtype (WHO grade IV) confirmed by central neuropathology review - near-complete resection (≤ 5 ml residual tumor volume) confirmed by central neuroradiologist on magnetic resonance imaging (MRI) scan within 72 h postoperative - patients ≥ 18 years of age - Karnofsky performance status (KPS) ≥ 70% or ≥ 50% and minimal mental state examination ≥ 25 - sterile tumor sample of ≥ 150 mg with tumor cell frequency ≥ 60% as determined by central neuropathologist available for vaccine production - successful production of sterile, avital tumor lysate - systemic corticosteroids tapered down to ≤ 2 mg of dexa-methasone or equivalent per day at baseline - adequate hepatic, liver and bone marrow function and blood coagulation - signed informed consent |
- neudiagnostiziertes, monofokales Glioblastom, Isozitratdehydrogenase Wildtyp (WHO Grad IV), das durch zentrale neuropathologische Überprüfung bestätigt wurde - fast vollständige Tumorresektion (≤ 5 ml Resttumor), bestätigt durch ein MRT innerhalb von 72 h und überprüft durch einen zentralen Neuroradiologen - Alter ≥ 18 Jahre - Karnofsky Status ≥ 70% oder ≥ 50% und minimal mental state examination ≥ 25 - sterile Tumorprobe mit ≥ 150 mg und Tumorzellanteil ≥ 60% (durch zentralen Neuropathologen bestätigt) für Vakzineherstellung verfügbar - systemische Kortikosteroide ≤ 2 mg/d Dexamethason oder äquivalent zur Baseline Visite - unterschriebene Einverständniserklärung |
|
E.4 | Principal exclusion criteria |
- medical history of severe acute or chronic disease with poor prognosis, autoimmune disorder, immunodeficiency or organ allograft - infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E (HEV) or Treponema pallidum or other severe infection requiring treatment -known allergy or intolerability to components of vaccine, to TMZ or to dacarbazine - severe myelosuppression - history of bleeding diathesis or coagulopathy - O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status equivocal |
- dokumentierte Vorgeschichte einer schwerwiegenden oder chronischen Erkrankung mit schlechter Prognose, Autoimmunerkrankung, Immundefizienz oder Organtransplantation - Infektion mit Humanem Immundefizienz Virus, Hepatitis B Virus, Hepatitis C Virus, Hepatitis E Virus, Treponema pallidum oder andere schwere Infektion, die einer Behandlung bedarf - bekannte Allergie für eine Komponente der Vakzine, für TMZ oder Dacarbazin - Schwere Myelosuppression - Vorgeschichte einer schweren Blutungsneigung oder anderen Gerinnungsstörung - O6-Methylguanin-DNA-Methyltransferase (MGMT) Promotormethylierungsstatus nicht eindeutig. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is overall survival (OS) measured from the day of surgery until death. |
Überleben, berechnet vom Tag der Operation bis zum Tod (OS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
from day of surgery until death |
vom Tag des Eingriffs bis zum Tod |
|
E.5.2 | Secondary end point(s) |
- progression-free survival (PFS) as measured from the day of surgery until diagnosis of tumor progression by MRI scan according to modified Response Assessment in Neuro-Oncology (RANO) criteria or death due to any cause - OS and PFS rates at 6, 12 and 24 months after the day of surgery - safety based on the frequency and severity of adverse events (AE) with toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 4.03 (CTCAE 4.03) - overall and neurological performance based on the Karnofsky performance status and the Minimal Mental State Examination 2 (MMSE-2) - quality of life as determined by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 3.0 and Brain Cancer Module QLQ-BN20 as well as the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS) for psycho-oncological strain assessment |
- Progressionsfreies Überleben (berechnet vom Tag der Operation bis zum dokumentierten Progress/Tod) - OS und PFS Raten 6, 12 and 24 Monate nach der Operation - Sicherheit basierend auf der Frequenz und Schwere von Nebenwirkungen bewertet entsprechend der National Cancer Institute Common Terminology Criteria for Adverse Events - gesamt- und neurologische Performance basierend auf dem Karnofsky Status und der Minimal Mental State Examination - Lebensqualität basierend auf dem European Organization for Research and Treatment of Cancer Quality of Life Questionnaire QLQ-C30 3.0 und Brain Cancer Module QLQ-BN20 sowie dem Distress Thermometer und dem Hospital Anxiety and Depression Scale für die Beurteilung der psychoonkologischen Belastung |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 12 and 24 months after the day of surgery |
6, 12 und 24 Monate nach dem Tag des Eingriffs |
|
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard Radiochemotherapie |
standard radiochemotherapy |
|
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
| 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 | 6 |
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 | 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
|
closure of data base |
Datenbankschluss |
|
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 | 63 |
E.8.9.1 | In the Member State concerned days | |