AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma (NANO-GBM)
Primary Purpose
Glioblastoma
Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Polysiloxane Gd-Chelates based nanoparticles (AGuIX)
radiotherapy
Temozolomide
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma
Eligibility 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.
- 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
Sites / Locations
- CHU de Brest
- Centre Jean PerrinRecruiting
- CHU de Grenoble
- Centre Léon Berard
- Institut de Cancérologie de l'Ouest
- Institut de Cancérologie Strasbourg Europe
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
AGuIX + chemoradiotherapy (radiotherapy + temozolomide)
chemoradiotherapy (radiotherapy + temozolomide)
Arm Description
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
standard of care : chemoradiotherapy (radiotherapy + temozolomide) for patients randomized in control arm of phase II
Outcomes
Primary Outcome Measures
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.
6-month Progression Free Survival (PFS) rate (phase II)
Secondary Outcome Measures
Pharmacokinetic Cmax of AGuIX
maximal plasma concentration (Cmax) of AGuIX
Pharmacokinetic Tmax of AGuIX
time of maximal plasma concentration (Tmax) of AGuIX
Pharmacokinetic AUC of AGuIX
Area Under the Curve (AUC) of AGuIX
Pharmacokinetic t1/2 of AGuIX
pharmacokinetic term half-life (t1/2) of AGuIX
distribution of AGuIX
measure of RMI contrast enhancement in tumor and healthy tissue
Overall Survival
Progression Free Survival (PFS)
Toxicity (CTCAE criteria)
according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria
Full Information
NCT ID
NCT04881032
First Posted
April 30, 2021
Last Updated
March 6, 2023
Sponsor
Centre Jean Perrin
Collaborators
Ministry for Health and Solidarity, France
1. Study Identification
Unique Protocol Identification Number
NCT04881032
Brief Title
AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Acronym
NANO-GBM
Official Title
Phase I/II Study of AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 7, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
March 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Jean Perrin
Collaborators
Ministry for Health and Solidarity, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase 1 : dose escalation Phase 2 : randomized
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AGuIX + chemoradiotherapy (radiotherapy + temozolomide)
Arm Type
Experimental
Arm Description
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
Arm Title
chemoradiotherapy (radiotherapy + temozolomide)
Arm Type
Sham Comparator
Arm Description
standard of care : chemoradiotherapy (radiotherapy + temozolomide) for patients randomized in control arm of phase II
Intervention Type
Drug
Intervention Name(s)
Polysiloxane Gd-Chelates based nanoparticles (AGuIX)
Intervention Description
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
Intervention Type
Radiation
Intervention Name(s)
radiotherapy
Intervention Description
60 Gy in 6 weeks
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
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 .
Primary Outcome Measure Information:
Title
The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period
Description
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.
Time Frame
during 6 weeks after the first injection of AGuIX
Title
6-month Progression Free Survival (PFS) rate (phase II)
Time Frame
6 months from the start of treatment
Secondary Outcome Measure Information:
Title
Pharmacokinetic Cmax of AGuIX
Description
maximal plasma concentration (Cmax) of AGuIX
Time Frame
Day 0 , Day 7, Day 14
Title
Pharmacokinetic Tmax of AGuIX
Description
time of maximal plasma concentration (Tmax) of AGuIX
Time Frame
Day 0 , Day 7, Day 14
Title
Pharmacokinetic AUC of AGuIX
Description
Area Under the Curve (AUC) of AGuIX
Time Frame
Day 0 , Day 7, Day 14
Title
Pharmacokinetic t1/2 of AGuIX
Description
pharmacokinetic term half-life (t1/2) of AGuIX
Time Frame
Day 0 , Day 7, Day 14
Title
distribution of AGuIX
Description
measure of RMI contrast enhancement in tumor and healthy tissue
Time Frame
after the first and last injection of AGuIX, Week 0 and Day 14
Title
Overall Survival
Time Frame
from the start of treatment to death, up to 24 months
Title
Progression Free Survival (PFS)
Time Frame
from the start of treatment to progression, up to 24 months
Title
Toxicity (CTCAE criteria)
Description
according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria
Time Frame
from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emilie Thivat
Phone
0473278089
Email
emilie.THIVAT@clermont.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juliette Moreau, Md
Organizational Affiliation
Centre Jean Perrin
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Brest
City
Brest
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
ZIP/Postal Code
63011
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julian Biau, MD
Facility Name
CHU de Grenoble
City
Grenoble
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Centre Léon Berard
City
Lyon
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Institut de Cancérologie de l'Ouest
City
Saint Herblain
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Institut de Cancérologie Strasbourg Europe
City
Strasbourg
Country
France
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Learn more about this trial
AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
We'll reach out to this number within 24 hrs