Clinical trial NCT04881032: AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Official title: Phase I/II Study of AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Lead sponsor: Centre Jean Perrin
Sponsor class: OTHER
Collaborators: name: Ministry for Health and Solidarity, France
First posted: 2021-05-11
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1 : dose escalation Phase 2 : randomized
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of grade IV glioblastoma (biopsy or partial surgery)
* Patient not operated or partial resection
* KPS superior to 70%
* Age between 18 years old and 75 years old
* Life expectancy superior to 6 months
* Platelets superior to 100,000 / mm3
* PNN superior to 1500 / mm3
* Hb superior to 10 g / dL
* Creatinine superior to 1.5 times the upper normal limit or clearance according to Cockcroft-Gault superior to 50 mL / min
* Liver function (GGT, PAL, ASAT, ALAT, bilirubin) superior to 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 disease or ulcerative colitis)
* Diarrhea superior to 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

Primary outcomes:
measure: The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period
timeFrame: during 6 weeks after the first injection of AGuIX
measure: 6-month Progression Free Survival (PFS) rate (phase II)
timeFrame: 6 months from the start of treatment
Secondary outcomes:
measure: Pharmacokinetic Cmax of AGuIX
timeFrame: Day 0 , Day 7, Day 14
measure: Pharmacokinetic Tmax of AGuIX
timeFrame: Day 0 , Day 7, Day 14
measure: Pharmacokinetic AUC of AGuIX
timeFrame: Day 0 , Day 7, Day 14
measure: Pharmacokinetic t1/2 of AGuIX
timeFrame: Day 0 , Day 7, Day 14
measure: distribution of AGuIX
timeFrame: after the first and last injection of AGuIX, Week 0 and Day 14
measure: Overall Survival
timeFrame: from the start of treatment to death, up to 24 months
measure: Progression Free Survival (PFS)
timeFrame: from the start of treatment to progression, up to 24 months
measure: Toxicity (CTCAE criteria)
timeFrame: from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)
Other outcomes:
Locations:
city: Brest
country: France
facility: CHU de Brest
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: Centre Léon Berard
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Paris
country: France
facility: Hôpital La Pitié Salpetrière
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
city: Strasbourg
country: France
facility: Institut de Cancérologie Strasbourg Europe
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Jean Perrin
name: Juliette Moreau, Md
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thivat E, Casile M, Moreau J, Molnar I, Dufort S, Seddik K, Le Duc G, De Beaumont O, Loeffler M, Durando X, Biau J. Phase I/II study testing the combination of AGuIX nanoparticles with radiochemotherapy and concomitant temozolomide in patients with newly diagnosed glioblastoma (NANO-GBM trial protocol). BMC Cancer. 2023 Apr 15;23(1):344. doi: 10.1186/s12885-023-10829-y.