GADOLINIUM-CHELATED POLYSILOXANE NANOPARTICLES for Glioblastoma

Inclusion criteria

• {"criterion_text":"- Histological diagnosis of grade IV glioblastoma (biopsy or partial surgery)\n- Patient not operated on or partial resection\n- KPS ≥ 70%\n- Age ≥ 18 years old and <75 years old\n- Life expectancy ≥ 6 months\n- Platelets ≥ 100,000 / mm3\n- Hb ≥ 10 g / L\n- Creatinine <1.5 times the upper normal limit or clearance according to Cockcroft-Gault ≥ 50 mL / min\n- Liver function : GGT, PAL, ASAT, ALAT <3 times the upper normal limit ; bilirubin <1.5 times the upper normal limit\n- For patients receiving treatment with corticosteroids, treatment with corticosteroids must be at a stable or decreasing dose for at least 14 days before inclusion\n- Patient able to swallow and retain oral medication\n- Negative serum pregnancy test within 7 days before the first administration of treatment for women\n- Women of childbearing potential and men whose partners are of childbearing potential must agree to use, themselves or their partners, an approved method of contraception throughout the treatment and at least 6 months after the last administration of study treatment.\n- Obtaining signed informed consent from the patient\n- Patient affiliated to a social security regimen"}

Exclusion criteria

• {"criterion_text":"- prior brain radiotherapy\n- prior chemotherapy (including implants containing carmustine (Gliadel®) or immunotherapy (vaccination included)\n- Any contraindication to TMZ listed in the SPCs\n- Current or recent treatment with another investigational drug or participation in another therapeutic clinical trial (within 30 days of inclusion).\n- History of other cancer in the 5 years preceding inclusion, except for basal cell carcinomas of the skin and in situ carcinomas of the cervix\n- Pregnant or breastfeeding women\n- Contraindication to MRI or gadolinium injection\n- History of severe anaphylactic reactions due to the injection of gadolinium-based contrast product (dotarem, etc.)\n- Patient under guardianship or curatorship\n- History of nephropathy\n- Psychological disorder or social or geographic reasons that may compromise medical monitoring of the trial or compliance with treatment"}

Primary endpoints

• {"endpoint_text":"- phase I : The recommended dose of AGuIX is defined as the highest dose tested in which the % of dose-limiting toxicities (DLT) is less than 33%. DLT is defined as any grade 3-4 toxicity, except alopecia, nausea, and vomiting, occuring during the first 6 weeks .","definition_or_measurement_approach":"Recommended dose defined as highest dose with DLT rate <33%. DLT = any grade 3-4 toxicity (except alopecia, nausea, vomiting) occurring during the first 6 weeks."}
• {"endpoint_text":"- phase II : 6-month Progression-free survival rate (RANO criteria)","definition_or_measurement_approach":"6-month progression-free survival measured using RANO criteria."}

Secondary endpoints

• {"endpoint_text":"- Pharmacokinetic parameters: Cmax, Tmax, AUC et T1/2","definition_or_measurement_approach":"Standard PK parameters (Cmax, Tmax, AUC, T1/2) to be measured in phase I."}
• {"endpoint_text":"- Distribution of nanoparticles : after the first and last injection of AGuIX (at S0 and S3). These MRIs will be optional for phase II depending on the participating centers.","definition_or_measurement_approach":"Imaging assessment (MRI) to evaluate nanoparticle distribution after first and last injections (S0 and S3); optional in phase II at some centers."}
• {"endpoint_text":"- Overalll survival since the start of treatment. assessment of median survival. The survival rate will be calculated at 6 and 12 months after the start of treatment.","definition_or_measurement_approach":"Overall survival from treatment start; median survival assessed; survival rates calculated at 6 and 12 months."}
• {"endpoint_text":"- the objective response rate according to RANO criteria.","definition_or_measurement_approach":"Objective response rate assessed per RANO criteria."}
• {"endpoint_text":"- The rate 12-month PFS","definition_or_measurement_approach":"12-month progression-free survival rate."}
• {"endpoint_text":"- the median of PFS","definition_or_measurement_approach":"Median progression-free survival."}
• {"endpoint_text":"- The safety profile of AGuIX nanoparticles in combination with radiotherapy and TMZ will be evaluated according to NCI CTC version 5.0 criteria throughout the study","definition_or_measurement_approach":"Safety assessed throughout study using NCI CTCAE v5.0 criteria."}
• {"endpoint_text":"- Neurological status will be assessed clinically and using the Mini- Mental State Examination (MMSE) questionnaire","definition_or_measurement_approach":"Neurological assessments plus MMSE questionnaire."}
• {"endpoint_text":"- The corticosteroid intake will also be evaluated","definition_or_measurement_approach":"Corticosteroid usage tracked and evaluated over time."}
• {"endpoint_text":"- The predictive biomarker and tumor microenvironment will be assessed on tumoral bloc (used for glioblastoma diagnosis)","definition_or_measurement_approach":"Assessment of predictive biomarkers and tumor microenvironment on diagnostic tumor block."}
• {"endpoint_text":"- local progression time, recurrence patterns (in-field, marginal, out-of-field)","definition_or_measurement_approach":"Time to local progression and analysis of recurrence patterns (in-field, marginal, out-of-field)."}

France

Earliest CTIS Part Ii Submission Date

31-12-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

407

Number Of Sites

8

Number Of Participants

66

Primary sponsor

Full Name

Centre Jean Perrin

Organisation Type

Patient organisation/association

Country Of Registered Address

France