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

NCT04881032 | Active Not Recruiting Phase 1

• 1 other identifier: 2020-004552-15
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 9

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• 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

• 6-month Progression Free Survival (PFS) rate (phase II)

  6 months from the start of treatment

Secondary Outcomes (8)

• Pharmacokinetic Cmax of AGuIX

  Day 0 , Day 7, Day 14

• Pharmacokinetic Tmax of AGuIX

  Day 0 , Day 7, Day 14

• Pharmacokinetic AUC of AGuIX

  Day 0 , Day 7, Day 14

• Pharmacokinetic t1/2 of AGuIX

  Day 0 , Day 7, Day 14

• distribution of AGuIX

  after the first and last injection of AGuIX, Week 0 and Day 14

Study Arms (2)

AGuIX + chemoradiotherapy (radiotherapy + temozolomide)

EXPERIMENTAL

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

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

chemoradiotherapy (radiotherapy + temozolomide)

SHAM COMPARATOR

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

Radiation: radiotherapy; Drug: Temozolomide

Interventions

Polysiloxane Gd-Chelates based nanoparticles (AGuIX) DRUG

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

AGuIX + chemoradiotherapy (radiotherapy + temozolomide)

radiotherapy RADIATION

60 Gy in 6 weeks

AGuIX + chemoradiotherapy (radiotherapy + temozolomide); chemoradiotherapy (radiotherapy + temozolomide)

Temozolomide DRUG

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 .

AGuIX + chemoradiotherapy (radiotherapy + temozolomide); chemoradiotherapy (radiotherapy + temozolomide)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Centre Jean Perrin: lead
• Ministry for Health and Solidarity, France: collaborator

Study Sites (9)

CHU de Brest

Brest, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

CHU de Grenoble

Grenoble, France

Location

Centre Léon Berard

Lyon, France

Location

Hospices Civils de Lyon

Lyon, France

Location

Hôpital La Pitié Salpetrière

Paris, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

Location

Institut de Cancérologie Strasbourg Europe

Strasbourg, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related 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.

  PMID: 37060055 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

AGuIX; Radiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Juliette Moreau, Md

  Centre Jean Perrin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 : dose escalation Phase 2 : randomized

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 11, 2021
• Study Start: March 7, 2022
• Primary Completion: September 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

FR (9)