Phase I/II study of AGuIX nanoparticles with radiotherapy plus concomitant Temozolomide in the treatment of newly diagnosed glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Jean Perrin

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Mar 2025 → ongoing

Decision date (initial)

2025-01-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Health Ministry (PHRC-I-19–060) · NHTheraguix

External identifiers

EU CT number

2024-517114-15-00

EudraCT number

2020-004552-15

ClinicalTrials.gov

NCT04881032

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

- 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 objectives 5

1. To evaluate the pharmacokinetics of nanoparticles (phase I)
2. To evaluate the distribution of nanoparticles and the sparing of healthy tissues
3. 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)
4. 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, local control and recurrence patterns (phase II)
5. To study the potential predictive biomarkers and exploration of the tumor microenvironment

Conditions and MedDRA coding

newly diagnosed gliblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Histological diagnosis of grade IV glioblastoma (biopsy or partial surgery)
2. Patient not operated on or partial resection
3. KPS ≥ 70%
4. Age ≥ 18 years old and <75 years old
5. Life expectancy ≥ 6 months
6. Platelets ≥ 100,000 / mm3
7. Hb ≥ 10 g / L
8. Creatinine <1.5 times the upper normal limit or clearance according to Cockcroft-Gault ≥ 50 mL / min
9. Liver function : GGT, PAL, ASAT, ALAT <3 times the upper normal limit ; bilirubin <1.5 times the upper normal limit
10. For patients receiving treatment with corticosteroids, treatment with corticosteroids must be at a stable or decreasing dose for at least 14 days before inclusion
11. Patient able to swallow and retain oral medication
12. Negative serum pregnancy test within 7 days before the first administration of treatment for women
13. 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.
14. Obtaining signed informed consent from the patient
15. Patient affiliated to a social security regimen

Exclusion criteria 11

1. prior brain radiotherapy
2. prior chemotherapy (including implants containing carmustine (Gliadel®) or immunotherapy (vaccination included)
3. Any contraindication to TMZ listed in the SPCs
4. Current or recent treatment with another investigational drug or participation in another therapeutic clinical trial (within 30 days of inclusion).
5. 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
6. Pregnant or breastfeeding women
7. Contraindication to MRI or gadolinium injection
8. History of severe anaphylactic reactions due to the injection of gadolinium-based contrast product (dotarem, etc.)
9. Patient under guardianship or curatorship
10. History of nephropathy
11. Psychological disorder or social or geographic reasons that may compromise medical monitoring of the trial or compliance with treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. phase I : The recommended dose of AGuIX 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, except alopecia, nausea, and vomiting, occuring during the first 6 weeks .
2. phase II : 6-month Progression-free survival rate (RANO criteria)

Secondary endpoints 11

1. Pharmacokinetic parameters: Cmax, Tmax, AUC et T1/2
2. Distribution of nanoparticles : after the first and last injection of AGuIX (at S0 and S3). These MRIs will be optional for phase II depending on the participating centers.
3. 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.
4. the objective response rate according to RANO criteria.
5. The rate 12-month PFS
6. the median of PFS
7. 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
8. Neurological status will be assessed clinically and using the Mini- Mental State Examination (MMSE) questionnaire
9. The corticosteroid intake will also be evaluated
10. The predictive biomarker and tumor microenvironment will be assessed on tumoral bloc (used for glioblastoma diagnosis)
11. local progression time, recurrence patterns (in-field, marginal, out-of-field)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Jean Perrin

Sponsor organisation

Centre Jean Perrin

Address

58 Rue Montalembert

City

Clermont-Ferrand

Postcode

63000

Country

France

Scientific contact point

Organisation

Centre Jean Perrin

Contact name

Emilie THIVAT

Public contact point

Organisation

Centre Jean Perrin

Contact name

Emilie THIVAT

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications