AGuIX Nanoparticles with Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma (NANO-GBM)

Centre Jean Perrin

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Glioblastoma

Treatments: Drug: Temozolomide; Drug: Polysiloxane Gd-Chelates based nanoparticles (AGuIX); Radiation: radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT04881032

2020-004552-15

Details and patient eligibility

About

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.

Enrollment: 66 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 2 patient groups

AGuIX + chemoradiotherapy (radiotherapy + temozolomide)

Experimental group

Description:

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

Treatment:

Radiation: radiotherapy

Drug: Polysiloxane Gd-Chelates based nanoparticles (AGuIX)

Drug: Temozolomide

chemoradiotherapy (radiotherapy + temozolomide)

Sham Comparator group

Description:

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

Treatment:

Radiation: radiotherapy

Drug: Temozolomide