| Eligibility |
Inclusion Criteria:
1. Signed informed consent form (ICF) prior to the start of any trial-related procedures.
2. Subject age = 18 years with an upper limit of 70 years.
3. In the Investigator's opinion, subject is able and willing to comply with all trial
requirements for the duration of the trial.
4. Suspected primary, newly diagnosed supratentorial GBM (Grade IV glioma per WHO
guidelines) based on signs/symptoms and MRI (obtained maximally 10 days prior to
surgery, using the same MRI settings as will be used for post-surgery MRI; if the MRI
is older than 10 days or if it is taken at a local clinic, this has to be repeated
within 10 days before the surgery), needing maximum safe resection followed by
chemoradiotherapy as per institutional guidelines (Stupp protocol: radiotherapy [60 Gy
total; 10 Gy per week for 6 weeks] plus concomitant TMZ [75 mg/m2 of body surface area
per day; 7 days per week from first to the last day of radiotherapy], followed by six
cycles of adjuvant TMZ [150 to 200 mg/m2] once daily for 5 consecutive days, followed
by 23 days of no treatment prior to the next cycle; or CeTeG protocol for MGMT
promoter methylated GBMs: up to six courses of lomustine [100 mg/m2 on Day 1 plus TMZ
[100-200 mg/m2 per day on Days 2-6 of the 6-week course] in addition to radiotherapy
[59-60 Gy], if preferred by the investigator).
5. Preliminary histological diagnosis of GBM by an intraoperative "frozen section",
analyzed during surgery is mandatory before administration of SI-053. A final
diagnosis is made by histopathological and molecular analysis of the resected tumor
tissue.
6. It is the surgeon's estimation that maximum safe resection of the contrast enhancing
part of the tumor with image-guided surgery is possible and it is not expected that
the ventricular system will be opened during surgery. When the ventricular system is
opened during surgery, no SI-053 will be administered.
7. The tumor volume as assessed by pre-surgery MRI is at least 10 mL, and the actual
resection bed volume based on the surgeon's estimation after surgery enables complete
administration of a single dose of SI-053.
8. Karnofsky Performance Status (KPS) score =70%
9. Women of childbearing potential (WOCBP) and men whose partner is of childbearing
potential must use effective contraception from the time of screening and for 6 months
after receiving SI-053. WOCBP should have a negative serum pregnancy test ß-human
chorionic gonadotropin (ß-HCG) at trial enrollment and within = 72 h before SI-053
administration.
10. Subjects must have following laboratory values obtained within 2 weeks prior to
enrollment.
• Acceptable liver function: Total bilirubin = 1.5 x upper limit of normal (ULN)
(except in the case of Gilbert's disease); Albumin 3.0 - 5.5 g/dL; Aspartate
transaminase (AST) = 2.5 x ULN
- Alanine transaminase (ALT) = 2.5 x ULN
- Alkaline phosphatase = 2.5 x ULN
- Acceptable kidney function: Creatinine clearance: = 30 mL/min (by CKD-EPI
formula)
- Acceptable hematologic status:
Absolute neutrophil count (ANC) = 1 500 cells/mm3 Platelet count = 100 000 cells/mm3
Hemoglobin = 10.0 g/dL
11. Subjects should have a suspected life expectancy of at least 6 months.
12. Documented negative test for HBV. For HBV serology, the determination of hBsAg and
anti-hBcAg Ab is required.
Exclusion Criteria:
- Subjects who fulfil any of the following criteria will be excluded from the trial:
1. Prior treatment for GBM including resection or radiation therapy.
2. Contraindications to radiation therapy or TMZ chemotherapy (i.e allergy,
hypersensitivity or other intolerabilities to TMZ and its excipients or
hypersensitivity to dacarbazine).
3. Has a history of another primary malignancy, except for:
- Malignancy treated with curative intent and with no known active disease
within 2 years prior to SI-053 administration
- Adequately treated non-invasive basal skin cancer or squamous cell skin
carcinoma
- Adequately treated uterine cervical cancer stage 1B or less
4. Has clinically significant cardiac disease (as identified by electrocardiogram
[ECG]), including:
- Known congestive heart failure Grade III or IV by the New York Heart Failure
Association;
- Myocardial infarction within 6 months prior to signing the ICF;
- Onset of unstable angina within 6 months prior to signing the ICF.
5. Infratentorial or multifocal glioblastoma.
6. Pre-operative MRI showing ventricular invasion (defined as presence of
intraventricular lesion or of intraventricular tumor mass).
7. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1.
8. Chronic use of systemic steroid therapy (>1 month of >10 mg prednisone per day or
equivalent, except topical or inhaled).
9. Any significant disease or disorder which, in the opinion of the Investigator,
may either put the participant at risk because of participation in the trial, or
affect the participant's ability to participate in the trial.
10. Subjects who have participated in another research trial involving an
investigational product within the past 12 weeks or are currently participating
in another clinical trial (excluding observational studies).
11. Pregnant or lactating women.
12. Subjects unable to undergo MRI during the trial participation
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