NANO-GBM: AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Study Details
Study Description
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
- 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 |
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 .
|
| Sham Comparator: chemoradiotherapy (radiotherapy + temozolomide) standard of care : chemoradiotherapy (radiotherapy + temozolomide) for patients randomized in control arm of phase II |
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 .
|
Outcome Measures
Primary Outcome Measures
- The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period [during 11 weeks after the first injection of AGuIX]
Only toxicities occurring during concomitant radiochemotherapy and the following 4 weeks 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.
- 6-month Progression Free Survival (PFS) rate (phase II) [6 months from the start of treatment]
Secondary Outcome Measures
- Pharmacokinetic Cmax of AGuIX [Day 0 , Day 7, Day 14]
maximal plasma concentration (Cmax) of AGuIX
- Pharmacokinetic Tmax of AGuIX [Day 0 , Day 7, Day 14]
time of maximal plasma concentration (Tmax) of AGuIX
- Pharmacokinetic AUC of AGuIX [Day 0 , Day 7, Day 14]
Area Under the Curve (AUC) of AGuIX
- Pharmacokinetic t1/2 of AGuIX [Day 0 , Day 7, Day 14]
pharmacokinetic term half-life (t1/2) of AGuIX
- distribution of AGuIX [after the first and last injection of AGuIX, Week 0 and Day 14]
measure of RMI contrast enhancement in tumor and healthy tissue
- Overall Survival [from the start of treatment to death, up to 24 months]
- Progression Free Survival (PFS) [from the start of treatment to progression, up to 24 months]
- Toxicity (CTCAE criteria) [from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)]
according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria
Eligibility Criteria
Criteria
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.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU de Brest | Brest | France | ||
| 2 | Centre Jean Perrin | Clermont-Ferrand | France | 63011 | |
| 3 | CHU de Grenoble | Grenoble | France | ||
| 4 | Centre Léon Berard | Lyon | France | ||
| 5 | Institut de Cancérologie de l'Ouest | Saint Herblain | France | ||
| 6 | Institut de Cancérologie Strasbourg Europe | Strasbourg | France |
Sponsors and Collaborators
- Centre Jean Perrin
- Ministry for Health and Solidarity, France
Investigators
- Principal Investigator: Juliette Moreau, Md, Centre Jean Perrin
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2020-004552-15