Clinical Trial Finder

Inclusion Criteria:

• - Histological diagnosis of grade IV glioblastoma (biopsy or partial surgery) - Patient not operated or partial resection.

• - KPS ≥ 70% - Age ≥ 18 years old and <75 years old.

• - Life expectancy ≥ 6 months.

• - Platelets ≥ 100,000 / mm3.

• - PNN ≥ 2000 / mm3.

• - Hb ≥ 10 g / dL.

• - Creatinine <1.5 times the upper normal limit or clearance according to Cockcroft-Gault ≥ 50 mL / min.

• - Liver function (GGT, PAL, ASAT, ALAT, bilirubin) <1.5 times the upper normal limit.

• - For patients receiving treatment with corticosteroids, treatment with corticosteroids must be at a stable or decreasing dose for at least 14 days before inclusion.

• - Patient able to swallow and retain oral medication.

• - Negative serum pregnancy test within 7 days before the first administration of treatment for women.

• - 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.

• - Obtaining signed informed consent from the patient.

• - Patient affiliated to a social security regimen.

Exclusion Criteria:

• - prior brain radiotherapy.

• - prior chemotherapy (including implants containing carmustine (Gliadel®) or immunotherapy (vaccination included) - Any contraindication to TMZ listed in the SPCs.

• - History of major intestinal resection which may modify the absorption of oral drugs according to the judgment of the investigator.

• - Diagnosed inflammatory bowel disease (Crohn's disease or ulcerative colitis) - Diarrhea ≥ grade 2 CTCAE (whatever the cause) - Current or recent treatment with another investigational drug or participation in another therapeutic clinical trial (within 30 days of inclusion).

• - 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.

• - Pregnant or breastfeeding women.

• - Contraindication to MRI or gadolinium injection.

• - History of severe anaphylactic reactions due to the injection of gadolinium-based contrast product (dotarem, etc.) - Patient under guardianship or curatorship.

• - History of nephropathy.

- Psychological disorder or social or geographic reasons that may compromise medical monitoring of the trial or compliance with treatment

Arms

Experimental: AGuIX + chemoradiotherapy (radiotherapy + temozolomide)

addition of AGuIX nanoparticles to standard radiotherapy and concomitant treatment by temozolomide (TMZ) for patients of phase I and patients randomized in experimental arm of phase II

Sham Comparator: chemoradiotherapy (radiotherapy + temozolomide)

standard of care : chemoradiotherapy (radiotherapy + temozolomide) for patients randomized in control arm of phase II

Interventions

Drug: - Polysiloxane Gd-Chelates based nanoparticles (AGuIX)

Four intravenous injections of AGuIX will be delivered. Phase I : Three dose levels may be explored 50 mg/kg, 75 mg/kg and 100 mg/ kg. Phase II : recommended dose

Radiation: - radiotherapy

60 Gy in 6 weeks

Drug: - Temozolomide

Concomitant chemotherapy consists of temozolomide (TMZ) at a dose of 75 mg per square meter per day, given 7 days per week from the first day of radiotherapy until the last day of radiotherapy. After a 4 week break after concomitant treatment, patient were then received up to 6 cycles of adjuvant TMZ according to the standard 5-day schedule every 28 days .