glioblastoma MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Gadolinium-chelated polysiloxane nanoparticles
Product Code: AGuIX
Pharmaceutical Form: Lyophilisate for solution for injection
Trade Name: temozolomide
Product Name: temozolomide
Pharm
Sponsors
Centre Jean Perrin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histological diagnosis of grade IV glioblastoma (biopsy or partial surgery) - Patient not operated on or partial resection - KPS = 70% - Age = 18 years old and =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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 -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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Phase I: to determine the recommended dose of AGuIX in combination with radiotherapy and TMZ during the concomitant radiochemotherapy period - Phase II: to estimate the efficacy of the combination radiochemotherapy + AGuIX (recommended dose), measured by the 6-month progression-free survival rate ;Secondary Objective: - To evaluate the pharmacokinetics of nanoparticles (phase I) - To evaluate the distribution of nanoparticles and the sparing of healthy tissues - To evaluate the safety of the combination: acute (<90 days) and late toxicity as well as changes in the dose and schedule of radiotherapy (phase I / II) - To evaluate the impact of the combination on efficacy: measured by overall survival at 6 months and 12 months, response to treatment and progression-free survival at 12 months (phase II) - To study the potential predictive biomarkers and exploration of the tumor microenvironment ;Primary end point(s): The recommended dose (phase I) of AGuIX in combination with TMZ and radiotherapy during the radio-chemotherapy period 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 according to the NCI CTCAE v5.0 classification, except alopecia, nausea, and vomiting which can be quickly controlled with appropriate measures. - 6-month Progression-free survival rate (PFS) (phase II): The rate of patients who have not presented a progression at 6 months from the starting treatment, i.e. 6 months after the first administration of AGuIX (at the recommended dose). Disease assessment will be based on the RANO criteria (Response Assessment in Neuro-Oncology) ;Timepoint(s) of evaluation of this end point: phase I : Only toxicities occurring during concomitant radiochemotherapy and the following 4 weeks will be considered for the evaluation of DLT (i.e. 11 weeks). phase II : 6-month Progression-free survival rate (PFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Pharmacokinetic parameters: Cmax, Tmax, AUC et T1/2 - Distribution of nanoparticles : after the first and last injection of AGuIX (at S0 and S3). - 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. - the objective response rate according to RANO criteria. - The rate 12-month PFS. - the median of PFS. - 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. - Neurological status will be assessed clinically and using the Mini-Mental State Examination (MMSE) questionnaire - The corticosteroid intake will also be evaluated. - The predictive biomarker and tumor microenvironment will be assessed on tumoral bloc (used for glioblastoma diagnosis) ;Timepoint(s) of evaluation of this end point: - Pharmacokinetic parameters: D0, D7, D14 - The distribution of nanoparticles : after the first and last injection of AGuIX (at S0 and S3). - The survival rate : at 6 and 12 months . - the rate 12-month PFS rate - The safety profile : throughout the study. | — |
Countries
France
Contacts
Public ContactDivision de Recherche Clinique
Centre Jean Perrin
Outcome results
None listed