Studien für das Tumorboard:
Köln: Neuroonkologisches Tumorboard

Diagnosen

Glioblastom

Einschlusskriterien

Patienten:

• Patienten mit neu diagnostiziertem Glioblastom (histologisch bestätigt durch Biopsie oder Resektion) innerhalb von 4 Wochen nach Diagnose
• Patienten mit wiederkehrendem Glioblastom innerhalb von 4 Wochen nach Diagnose des Rezidivs
• Eastern Cooperative Oncology Group (ECOG) Skala: 0-2
• Alter ≥ 18 Jahre
• Fähigkeit, die deutsche Sprache zu verstehen, lesen und auf Deutsch zu antworten
• Fähigkeit schriftliches Einverständnis zu geben

Angehörige:

• Person (Verwandte oder andere eng vertraute Person) von besonderer Bedeutung für den Patienten, d.h. zusammenlebend oder mindestens zwei Mal die Woche persönlicher Kontakt mit dem Patienten. (Cave: Patienten können auch eingeschlossen werden, wenn solch eine Person nicht existiert.)
• Eastern Cooperative Oncology Group (ECOG) Skala: 0-2
• Alter ≥ 18 Jahre
• Fähigkeit, die deutsche Sprache zu verstehen, lesen und auf Deutsch zu antworten
• Fähigkeit schriftliches Einverständnis zu geben

Sonstiges

Kontaktpersonen

Hartmut.Vatter@ukb.uni-bonn.de
roland.goldbrunner@uk-koeln.de
charlotte.nettekoven@uk-koeln.de
Ulrich.Herrlinger@ukb.uni-bonn.de
Michael.Sabel@med.uni-duesseldorf.de
lena.koschnitzke@med.uni-duesseldorf.de

Ausschlusskriterien

Patienten und Angehörige:

• Widerwillen sich an das Studienprotokoll zu halten
• Geschäftsunfähigkeit
• Andauernder Gebrauch von Drogen oder Alkohol oder psychiatrische Erkrankung, die den Patienten oder Angehörigen nach Einschätzung des Prüfers für die Studienteilnahme ungeeignet macht
• Jegliche Abhängigkeit von den Prüfern oder angestellt durch den Sponsor oder Prüfer
• rechtliche oder behördliche Unterbringung in einer Anstalt

Diagnosen

Glioblastom

Einschlusskriterien

1. Written informed consent
2. Age ≥18 years
3. Patient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery or biopsy
4. Patient agrees to subcutaneous port implantation
5. Newly diagnosed, histologically confirmed, supratentorial WHO grade IV glioblastoma
6. Status post biopsy or incomplete resection
7. Unmethylated MGMT promoter status
8. Maximum Eastern Cooperative Oncology Group (ECOG) score 2
9. Estimated minimum life expectancy 3 months
10. Stable or decreasing dose of corticosteroids during the week prior to inclusion

11. The following laboratory parameters should be within the ranges specified:

    • Total bilirubin ≤ 1.5 x upper limit normal (ULN)
    • Creatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m²
    • ALT (alanine transaminase) ≤ 3 x ULN
    • AST (aspartate transaminase) ≤ 3 x ULN
12. Female patients of child-bearing potential must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly such as contraceptive implants, vaginal rings, sterilization, or sexual abstinence)" during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)
13. Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP

Sonstiges

Studienerweiterung:

Arm A: Olaptesed + Bevacizumab

Arm B: Olaptesed

Arm C. Olaptesed + Pembrolizumab

Kontaktpersonen

Ulrich.Herrlinger@ukb.uni-bonn.de
frank.giordano@ukbonn.de

Ausschlusskriterien

1. Inability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements
2. Participation in any clinical research study with administration of an investigational drug or therapy within 30 days from screening visit or observation period of competing studies
3. Contra-indication or known hypersensitivity to MRI contrast agents, olaptesed pegol or polyethylene glycol
4. Cytostatic therapy (chemotherapy) within the past 5 years
5. History of other cancers (except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient was disease-free for ≥ 5 years)
6. Clinically significant or uncontrolled cardiovascular disease
7. Prior radiotherapy to the head
8. Any other previous or concomitant experimental glioblastoma treatments
9. Placement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles
10. Pregnancy or lactation
11. Uncontrolled intercurrent illness; patients must be free of any clinically relevant disease (other than glioma) that would, in the treating investigator's opinion, interfere with the conduct of the study or study evaluations
12. Treatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma
13. Prior enrolment into this study

Diagnosen

Glioblastom, Gliom

Einschlusskriterien

• histologisch bestätigtes Glioblastom IV mit  unmethyliertem MGMT promoter
• offene Biopsie/Resektion
• die Kraniotomie oder intrakranielle Biopsie muss ausreichend ausgeheil sein
• Standard MRT 48 h (+6H) nach Operation gemäß der nationalen und internationalen Guidelines
• KPS ≥70%
• Lebenserwartung > 6 Monate

Sonstiges

Bestrahlung über 30 Tage

Kontaktpersonen

roland.goldbrunner@uk-koeln.de
stefanie.margane@uk-koeln.de
marco.timmer@uk-koeln.de
julia.homey@uk-koeln.de
Ulrich.Herrlinger@ukb.uni-bonn.de
Christiane.Landwehr@ukbonn.de

Ausschlusskriterien

•  Unfähigkeit, sich einer MRT zu unterziehen.
• Abnormale (≥ CTCAE v4.03 Grad 2) Laborwerte für Hämatologie (Hb, WBC, Neutrophile oder Thrombozyten), Leber (Serum-Bilirubin, ALT oder AST) oder Nierenfunktion (Serum-Kreatinin).
• Immunsuppression, nicht im Zusammenhang mit der vorherigen Behandlung von Malignomen
•  HIV- oder Hepatitisinfektion

Diagnosen

Glioblastom

Einschlusskriterien

Schriftliche Einwilligung des Patienten nach umfänglicher Aufklärung

Alter ab 18 - ≤ 70 Jahre

Primäre supratentoriale Glioblastome, nach abgeschlossener
Standardtherapie (Fluoreszenz-gesteuerte Resektion, Radio-
Chemotherapie, Begleit- + Adjuvant Chemotherapie), ohne oder mit
geringem Resttumor (Tumorvolumen  1,0 cm3) mindestens 6 Monate
nach der Operation

 Histologischer Nachweis eines Glioblastoms und immunhistologische
Bestätigung der CA12-Expression des Tumorgewebes

Karnofsky-Score ≥ 70

Volumen der Resektionshöhle 5-25 cm3

Männliche und weibliche Patienten mit reproduktivem Potenzial müssen
eine anerkannte Verhütungsmethode anwenden (s. Protokoll)

Frauen vor der Menopause mit gebärfähigem Potenzial: Vor Beginn der
Behandlung muss ein negativer Schwangerschaftstest vorliegen

Ausreichende Knochenmarkreserve:
Leukozytenzahl ≥3000 /μl,
Granulozytenzahl > 1500 /μl,
Thrombozyten ≥100.000 /μl,
Hämoglobin ≥ 10 g /dl

Angemessene Leberfunktion:
Bilirubin < 1,5 x obere Normgrenze (ULN),
Alanin-Transaminase (ALT / SGPT) und Aspartat-Transaminase
(AST/SGOT) < 3 x obere Normgrenze.
Bei dokumentiertem oder Verdacht auf Gilbert-Krankheit
Bilirubin < 3 x obere Normgrenze ULN.

Blutgerinnung:
INR (=PT) und PTT innerhalb akzeptabler Grenzen, im Ermessen des
Prüfers

Angemessene Nierenfunktion:
Kreatinin < 3 x obere Normgrenze (ULN),
eGFR ≥ 60 ml / min

Sonstiges

Kontaktpersonen

julia.homey@uk-koeln.de
marco.timmer@uk-koeln.de
simone.stockter@uk-koeln.de

Ausschlusskriterien

Patienten bei denen die Durchführung eins CT, PET oder Kontrastmittelangereichertem MRT nicht möglich ist (z. B. Schrittmacher)

GBM mit intraventrikulärem Zugang

Signifikantes Übertreten der Radioaktivität (leakage) aus der Resektionshöhle in die Ventrikel oder den subarachnoidalen Raum

andere invasive Malignität innerhalb von 2 Jahren (mit Ausnahme von
nichtinvasiven Malignitäten wie Zervixkarzinom in situ, nicht melanomatösem Hautkarzinom oder duktalem Karzinom in situ der operativ geheilten Brust)

Stillende Frauen

Zurückliegende Erkrankung mit schlechter Prognose, z.B. schwere
Koronarinzuffizienz, Herzinsuffizienz (NYHA III / IV), schwerer und schlecht
kontrollierter Diabetes, Immunsuffizienz, Defizite nach einem Schlaganfall,
schwere mentale Retardierung, vorbestehende neurologische Erkrankung
ausgenommen solche in Zusammenhang mit dem Glioblastom oder andere
schwerwiegende systemische Störungen, die eine Teilnahme an der Studie
nicht erlauben (im Ermessen des Prüfers)

Eine aktive Infektion (nach Ermessen des Prüfers)

Teilnahme an einer anderen klinischen Studie mit therapeutischer
Intervention oder Verwendung einer anderen therapeutischen Intervention
als der Standardtherapie seit der Diagnose des Glioblastoms

Allergie gegen einen der bekannten Bestandteile der Prüfmedikation

Diagnosen

Glioblastom

Einschlusskriterien

1. Patients with unequivocal documented (including histological confirmation of Glioblastoma-GB- at the primary diagnosis) evidence of progressive or first recurrent GB on MRI, as defined by RANO criteria
2. Patients with at least 1 measurable lesion
3. Patients with an age ≥ 18 years old
4. Patients who are human leukocyte antigen (HLA)-A2 positive
5. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky performance status ≥ 70

6. Patients should have received standard therapy, including surgery (biopsy, incomplete or complete resection), radiation, temozolomide, if applicable

   1. Radiation therapy must have been finished 28 days before first study treatment administration
   2. Patients who received temozolomide as adjuvant therapy must have stopped the treatment and have a wash-out period of 28 days before first study treatment administration (6 weeks for nitrosoureas and 5 half lives for experimental therapies)
   3. Patients with unmethylated methylguanine-DNA-methyltransferase (MGMT) promoter can be included even if they have not received temozolomide prior to the inclusion in this clinical study)
7. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to dosing

8. Considering the embryofetal toxicity of the nivolumab shown on animals' models, the following recommendations for contraception must be followed:

   a. If not surgically sterile, female patients of childbearing potential age must use highly effective barrier contraception from signing the Informed Consent Form (ICF) through 6 months after the last treatment dose administered. Highly effective barrier and non barrier contraception included: i. Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: Oral Intravaginal Transdermal ii. Progestogen-only hormonal contraception associated with inhibition of ovulation: Oral Injectable Implantable iii. Intrauterine device iv. Intrauterine hormone-releasing system v. Bilateral tubal occlusion vi. Sexual abstinence. In each case of delayed menstrual period (over 1 month between menstruations), confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles.

   b. If not surgically sterile, male with female partner of childbearing potential must use condom from signing the ICF through 8 months after the last treatment dose administered. Males must ensure that their partners of childbearing potential use highly effective barrier contraception also.

9. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures
10. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

Sonstiges

Kontaktpersonen

Christiane.Landwehr@ukbonn.de

Ausschlusskriterien

1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of prednisone) within 14 days before the first EO2401 administration, unless required to treat an adverse event (AE) Note: The criterion is applicable at the time of screening and also at the time of study treatment start (i.e. the patient should not have received treatment with dexamethasone > 2 mg/day or equivalent in the time between screening and study treatment start; this should be checked at the time of treatment start).
2. Patients treated with PD (L)-1(Programmed-cell Death/Programmed-cell Death Ligand) immunotherapy, radiotherapy, and cytoreductive therapy within 28 days before the first EO2401 administration
3. Patients with tumors primarily located in the infra-tentorial segment
4. Patients with known radiological evidence of extracranial metastases
5. Patients with presence of new hemorrhage (excluding, stable Grade 1) or uncontrolled seizure
6. Patients with significant leptomeningeal disease

7. Patients with abnormal (≥ Grade 2 National Cancer Institute-Common Terminology Criteria for AEs [NCI-CTCAE] version 5.0) laboratory values for hematology, liver, and renal function (serum creatinine). In detail, the following values apply as exclusion criteria:

   1. Hemoglobin < 10 g/dL (6.2 mmol/L)
   2. White blood cell count decrease (< 3.0 × 109/L) or increase (> 10.0 × 109/L)
   3. Absolute neutrophil count decrease (< 1.5 × 109/L)
   4. Platelet count decrease (< 75 × 109/L)
   5. Bilirubin > 1.5 × upper limit of normal (ULN; according to the performing laboratory's reference ranges)
   6. Alanine aminotransferase > 3 × ULN
   7. Aspartate aminotransferase > 3 × ULN
   8. Gamma-glutamyltransferase > 2.5 × ULN
   9. Serum creatinine increase (> 1.5 × ULN)
   10. Abnormal thyroid function: 0.3 > thyroid-stimulating hormone > 5 μU(μunit)/mL and 1.07 > free T3 > 3.37 nmol/L and 8.6 > free T4 > 25 pmol/L.

8. For patients who are planned to receive bevacizumab:

   1. Patients with nephrotic syndrome
   2. Patients with proteinuria ≥ 2g/24 hours
   3. Patients with history or active gastrointestinal perforation and fistula
   4. Significant surgical procedure in the 4 weeks preceding the start of treatment or planned surgery
   5. Unhealed wound
   6. Patient with recent (4 weeks) history of hemoptysis of ½ teaspoon or more of red blood
   7. Thrombotic episode within 6 months
   8. Uncontrolled diabetes mellitus or hypertension
   9. Posterior reversible encephalopathy syndrome
9. Patients with persistent Grade 3 or 4 toxicities (according to NCI-CTCAE v5.0). Toxicities must be resolved since at least 2 weeks to Grade 1 or less. However, alopecia or other persisting toxicities Grade ≤ 2 not constituting a safety risk based on Investigator's judgment is acceptable
10. Patients with contraindication to contrast-enhanced MRI
11. Other malignancy or prior malignancy with a disease-free interval of less than 3 years except those treated with surgical intervention and an expected low likelihood of recurrence such as basal cell or squamous cell skin cancer, or carcinoma in situ. Patients with adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ are eligible

12. Patients with clinically significant cardiac disease, significant medical or psychiatric disease/condition that, in the opinion of the Investigator, would interfere with the evaluation of EO2401 or interpretation of patient safety or study results or that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol - including (but not limited to):

    1. New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry
    2. Uncontrolled or significant cardiovascular disease, including:

    i. Myocardial infarction within 6 months prior to obtaining informed consent ii. Uncontrolled angina within 6 months prior to obtaining informed consent iii. Diagnosed or suspected congenital long QT syndrome iv. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) v. Unstable angina within 6 months prior to obtaining informed consent. c. Stroke within 6 months prior obtaining informed consent d. Concurrent neurodegenerative disease e. Dementia or significantly altered mental status.

13. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g., Guillain-Barré syndrome)
14. Patients with vitiligo, type I diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
15. Patients with history of solid organ transplantation or hematopoietic stem cell transplantation
16. Patients with history or known presence of tuberculosis
17. Pregnant and breastfeeding patients
18. Patients with history or presence of human immunodeficiency virus and/or hepatitis B virus/hepatitis C virus
19. Patients who have received live or attenuated vaccine therapy used for prevention of infectious diseases including seasonal (influenza) vaccinations within 4 weeks of the first dose of study drug
20. Patients with a history of hypersensitivity to any excipient present in the pharmaceutical form of investigational medicinal product
21. Patients treated with herbal remedies with immunostimulating properties or known to potentially interfere with major organ function
22. Patients with known drug and alcohol abuse
23. Patients with known or underlying medical or psychiatric condition that, in the Investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or AEs
24. Patients who have received treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrollment and during the treatment period
25. Patients deprived of their liberty or under protective custody or guardianship.

Diagnosen

Glioblastom

Einschlusskriterien

•  Neu diagnostizierte histologisch bestätigte GBM (WHO-Grad IV)
• Patient innerhalb der ersten 3 Zyklen der Erstlinien-tumorspezifischen Erhaltungs-Chemotherapie
• ≥ 18 Jahre alt
•  Klinische Indikation für die Behandlung mit TTFields
• erfolgte Einverständniserklärung für die Verwendung und Verarbeitung von Daten

Sonstiges

Kontaktpersonen

Michael.Sabel@med.uni-duesseldorf.de

Ausschlusskriterien

Vorhandene oder geplante Schwangerschaft

Signifikante zusätzliche neurologische Erkrankung (zB signifikant erhöhter intrazerebraler Druck (ICP) mit signifikanter Mittellinienverschiebung des Gehirns)

Aktiv implantiertes medizinisches Gerät (zB Tiefenhirnstimulator)

Dokumentierte Allergie gegen leitfähiges Hydrogel

Schädeldefekt (zB fehlender Knochen ohne Ersatz, Kugelfragmente im Schädel)