This is a phase I/II clinical trial evaluating the association of AGuIX nanoparticles with radiotherapy plus concomitant Temozolomide in the treatment of newly diagnosed glioblastoma. The primary objectives of this study were to determine the recommended dose of AGuIX in combination with radiotherapy and TMZ during the concomitant radiochemotherapy period (phase I) and to estimate the efficacy of the combination radiochemotherapy + AGuIX (recommended dose), measured by the 6-month progression-free survival rate (PFS) (phase II) Three dose levels of intravenous AGuIX nanoparticles will be explored: 50 mg/kg, 75 mg/kg and 100 mg/kg.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
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
60 Gy in 6 weeks
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 .
CHU de Brest
Brest, France
Centre Jean Perrin
Clermont-Ferrand, France
CHU de Grenoble
Grenoble, France
Centre Léon Berard
Lyon, France
Hospices Civils de Lyon
Lyon, France
Hôpital La Pitié Salpetrière
Paris, France
Institut de Cancérologie de l'Ouest
Saint-Herblain, France
Institut de Cancérologie Strasbourg Europe
Strasbourg, France
Institut Gustave Roussy
Villejuif, France
The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period
Only toxicities occurring during concomitant radiochemotherapy will be considered for the evaluation of Dose Limiting Toxicity 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.
Time frame: during 6 weeks after the first injection of AGuIX
6-month Progression Free Survival (PFS) rate (phase II)
Time frame: 6 months from the start of treatment
Pharmacokinetic Cmax of AGuIX
maximal plasma concentration (Cmax) of AGuIX
Time frame: Day 0 , Day 7, Day 14
Pharmacokinetic Tmax of AGuIX
time of maximal plasma concentration (Tmax) of AGuIX
Time frame: Day 0 , Day 7, Day 14
Pharmacokinetic AUC of AGuIX
Area Under the Curve (AUC) of AGuIX
Time frame: Day 0 , Day 7, Day 14
Pharmacokinetic t1/2 of AGuIX
pharmacokinetic term half-life (t1/2) of AGuIX
Time frame: Day 0 , Day 7, Day 14
distribution of AGuIX
measure of RMI contrast enhancement in tumor and healthy tissue
Time frame: after the first and last injection of AGuIX, Week 0 and Day 14
Overall Survival
Time frame: from the start of treatment to death, up to 24 months
Progression Free Survival (PFS)
Time frame: from the start of treatment to progression, up to 24 months
Toxicity (CTCAE criteria)
according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria
Time frame: from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)
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