Multispectral Bimodal Fluorescence Guided Surgery of High-grade Glioma With Cetuximab-800CW and 5-ALA (5-aminolevulinic Acid)

Inclusion Criteria:

• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• Capable of giving signed informed consent (voluntarily), indicating that the patientunderstands the purpose and procedures required for the study and is willing to complywith the requirements and restrictions listed in the informed consent form and in thisprotocol.
• Patients aged ≥ 18 years inclusive at moment signing informed consent form.
• Established high-grade glioma (glioblastoma, grade 4 according to the WHO (WorldHealth Organization) classification) and scheduled for surgical intervention.
• Life expectancy of > 12 weeks.
• Karnofsky performance status of at least 70%.
• No clinically significant laboratory abnormalities as determined by the investigator o Note: one retest of lab tests is allowed within the screening window
• Female patients should fulfil one of the following criteria:
• At least 1 year post-menopausal (amenorrhea >12 months) at screening
• Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation)
• Women >18 years of age who are fertile, need to agree to use an adequate form ofcontraceptives during and till 3 months after the study. Before study enrollment,a pregnancy test in blood or urine will be performed to rule out a pregnancy. Inthe case of an unlikely pregnancy during the study, they accept the possiblematernal/ fetal risk of participation in the study.

Exclusion Criteria: General:

• Behavioral or cognitive impairment or psychiatric disease that in the opinion of theinvestigator affects the ability of the patient to understand and cooperate with thestudy protocol
• Deprived of freedom by an administrative or court order or in an emergency setting.
• Insufficient venous access for the study procedures.
• Close affiliation with the investigator; e.g. a close relative of the investigator,dependent person (e.g. employee or student), employee of the department ofNeurosurgery of the UMCG (University Medical Center Groningen), or affiliates
• Any finding in the medical examinations or medical history giving, that in the opinionof the investigator, leads to a reasonable suspicion of a disease or condition thatmakes treatment with the investigational drug unadvisable, or that might affectinterpretation of the results of the study or render the patient at high risk fortreatment complications
• Participation in an interventional clinical study within 30 days prior to traceradministration that involved treatment with any drug (excluding vitamins and minerals)or medical device Medical conditions
• Concomitant malignancies, including metastasized colon-, rectal-, breast carcinoma,non-small cellular lung carcinoma (NSCLC); primary epithelial ovarian-, fallopiantube-, primary peritoneal- or cervical carcinoma.
• Any abnormalities in the vital signs of the patient, as judged by the investigator, asa result of which the patient cannot participate
• eGFR (based on plasma-creatinine) outside of normal range at screening or known renalimpairment (≤40 mL/min).
• Current evidence or history of bacterial, viral or fungal infections within 7 daysbefore Cetuximab-IRDye800CW administration, as judged by the Investigator. o T > = 38.0°C or lab confirmed viral/bacterial/fungal infection (PCR)) or symptomssuggestive of an infection)
• Any laboratory test which is abnormal, and which is deemed by the Investigator(s) tobe clinically significant
• A history of anaphylaxis, history of allergic reaction(s), known allergy to one of thedrugs or excipients administered as part of this study. Mild allergies withoutangioedema or treatment need can be acceptable if deemed not to be of clinicalsignificance (including but not limited to allergy to animals or mild seasonal hayfever)