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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04881032




Registration number
NCT04881032
Ethics application status
Date submitted
30/04/2021
Date registered
11/05/2021
Date last updated
1/10/2024

Titles & IDs
Public title
AGuIX Nanoparticles with Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Scientific title
Phase I/II Study of AGuIX Nanoparticles with Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Secondary ID [1] 0 0
2020-004552-15
Universal Trial Number (UTN)
Trial acronym
NANO-GBM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Polysiloxane Gd-Chelates based nanoparticles (AGuIX)
Treatment: Other - radiotherapy
Treatment: Drugs - Temozolomide

Experimental: AGuIX + chemoradiotherapy (radiotherapy + temozolomide) - 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

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


Treatment: Drugs: 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

Treatment: Other: radiotherapy
60 Gy in 6 weeks

Treatment: Drugs: 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 .
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period
Timepoint [1] 0 0
during 6 weeks after the first injection of AGuIX
Primary outcome [2] 0 0
6-month Progression Free Survival (PFS) rate (phase II)
Timepoint [2] 0 0
6 months from the start of treatment
Secondary outcome [1] 0 0
Pharmacokinetic Cmax of AGuIX
Timepoint [1] 0 0
Day 0 , Day 7, Day 14
Secondary outcome [2] 0 0
Pharmacokinetic Tmax of AGuIX
Timepoint [2] 0 0
Day 0 , Day 7, Day 14
Secondary outcome [3] 0 0
Pharmacokinetic AUC of AGuIX
Timepoint [3] 0 0
Day 0 , Day 7, Day 14
Secondary outcome [4] 0 0
Pharmacokinetic t1/2 of AGuIX
Timepoint [4] 0 0
Day 0 , Day 7, Day 14
Secondary outcome [5] 0 0
distribution of AGuIX
Timepoint [5] 0 0
after the first and last injection of AGuIX, Week 0 and Day 14
Secondary outcome [6] 0 0
Overall Survival
Timepoint [6] 0 0
from the start of treatment to death, up to 24 months
Secondary outcome [7] 0 0
Progression Free Survival (PFS)
Timepoint [7] 0 0
from the start of treatment to progression, up to 24 months
Secondary outcome [8] 0 0
Toxicity (CTCAE criteria)
Timepoint [8] 0 0
from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)

Eligibility
Key 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 = 1500 / 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2027
Actual
Sample size
Target
Accrual to date
Final
66
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Brest
Country [2] 0 0
France
State/province [2] 0 0
Clermont-Ferrand
Country [3] 0 0
France
State/province [3] 0 0
Grenoble
Country [4] 0 0
France
State/province [4] 0 0
Lyon
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
France
State/province [6] 0 0
Saint Herblain
Country [7] 0 0
France
State/province [7] 0 0
Strasbourg
Country [8] 0 0
France
State/province [8] 0 0
Villejuif

Funding & Sponsors
Primary sponsor type
Other
Name
Centre Jean Perrin
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Ministry for Health and Solidarity, France
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04881032
Trial related presentations / publications
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.
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Juliette Moreau, Md
Address 0 0
Centre Jean Perrin
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04881032