AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma

Glioblastoma Clinical Trial

— NANO-GBM  

Official title:

Phase I/II Study of AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04881032
• Other study ID #: 2020-004552-15
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 7, 2022
• Est. completion date: March 2027

Study information

• Verified date: March 2024
• Source: Centre Jean Perrin
• Contact: Emilie Thivat
• Phone: 0473278089
• Email: emilie.THIVAT[@]clermont.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: March 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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 .

Locations

Country	Name	City	State
France	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

Sponsors (2)

Lead Sponsor	Collaborator
Centre Jean Perrin	Ministry for Health and Solidarity, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	during 6 weeks after the first injection of AGuIX
Primary	6-month Progression Free Survival (PFS) rate (phase II)		6 months from the start of treatment
Secondary	Pharmacokinetic Cmax of AGuIX	maximal plasma concentration (Cmax) of AGuIX	Day 0 , Day 7, Day 14
Secondary	Pharmacokinetic Tmax of AGuIX	time of maximal plasma concentration (Tmax) of AGuIX	Day 0 , Day 7, Day 14
Secondary	Pharmacokinetic AUC of AGuIX	Area Under the Curve (AUC) of AGuIX	Day 0 , Day 7, Day 14
Secondary	Pharmacokinetic t1/2 of AGuIX	pharmacokinetic term half-life (t1/2) of AGuIX	Day 0 , Day 7, Day 14
Secondary	distribution of AGuIX	measure of RMI contrast enhancement in tumor and healthy tissue	after the first and last injection of AGuIX, Week 0 and Day 14
Secondary	Overall Survival		from the start of treatment to death, up to 24 months
Secondary	Progression Free Survival (PFS)		from the start of treatment to progression, up to 24 months
Secondary	Toxicity (CTCAE criteria)	according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria	from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)