A Dose Escalation Study to Estimate MTD, DLTs and Pharmacokinetics After a Single Intracranial Do… (NCT04967690) | Clinical Trial Compass
UnknownPhase 1
A Dose Escalation Study to Estimate MTD, DLTs and Pharmacokinetics After a Single Intracranial Dose of SI-053 as an add-on to the Current Standard of Care, in Adult Patients With Newly Diagnosed GBM
27 participantsStarted 2024-01
Plain-language summary
SI-053 is a novel powder formulation containing temozolomide (TMZ), an alkylating chemotherapy agent, in an excipient which forms a viscous gel upon reconstitution in water. SI-053 will be used as an add-on to SoC for newly diagnosed GBM. SoC consists of maximal safe resection followed by radiation therapy (RT) with concomitant TMZ and adjuvant chemotherapy with TMZ. For MGMT promoter methylated GBM, lomustine and TMZ may be administered plus radiation therapy
Who can participate
Age range18 Years – 70 Years
SexALL
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Inclusion criteria
✓. Signed informed consent form (ICF) prior to the start of any trial-related procedures.
✓. Subject age ≥ 18 years with an upper limit of 70 years.
✓. In the Investigator's opinion, subject is able and willing to comply with all trial requirements for the duration of the trial.
✓. 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).
✓. 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.
✓. 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.
✓. 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.
What they're measuring
1
Incidence rate and the grade (severity) of dose-limiting toxicities (DLTs) of a single i.c dose of SI-053
✓. Karnofsky Performance Status (KPS) score ≥70%
Exclusion criteria
✕. Prior treatment for GBM including resection or radiation therapy.
✕. Contraindications to radiation therapy or TMZ chemotherapy (i.e allergy, hypersensitivity or other intolerabilities to TMZ and its excipients or hypersensitivity to dacarbazine).
✕. Has a history of another primary malignancy, except for:
✕. Has clinically significant cardiac disease (as identified by electrocardiogram \[ECG\]), including:
✕. Infratentorial or multifocal glioblastoma.
✕. Pre-operative MRI showing ventricular invasion (defined as presence of intraventricular lesion or of intraventricular tumor mass).
✕. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1.
✕. Chronic use of systemic steroid therapy (\>1 month of \>10 mg prednisone per day or equivalent, except topical or inhaled).