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AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma (NANO-GBM)

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ClinicalTrials.gov Identifier: NCT04881032
Recruitment Status : Not yet recruiting
First Posted : May 11, 2021
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
French Ministry of Health (PHRCI-19-060)
Information provided by (Responsible Party):
Centre Jean Perrin

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.


Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Polysiloxane Gd-Chelates based nanoparticles (AGuIX) Radiation: radiotherapy Drug: Temozolomide Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 1 : dose escalation Phase 2 : randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of AGuIX Nanoparticles With Radiotherapy Plus Concomitant Temozolomide in the Treatment of Newly Diagnosed Glioblastoma
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine


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 .





Primary Outcome Measures :
  1. The recommended dose (phase I) of AGuIX in combination with TMZ and and radiotherapy during the radio-chemotherapy period [ Time Frame: 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.

  2. 6-month Progression Free Survival (PFS) rate (phase II) [ Time Frame: 6 months from the start of treatment ]

Secondary Outcome Measures :
  1. Pharmacokinetic Cmax of AGuIX [ Time Frame: Day 0 , Day 7, Day 14 ]
    maximal plasma concentration (Cmax) of AGuIX

  2. Pharmacokinetic Tmax of AGuIX [ Time Frame: Day 0 , Day 7, Day 14 ]
    time of maximal plasma concentration (Tmax) of AGuIX

  3. Pharmacokinetic AUC of AGuIX [ Time Frame: Day 0 , Day 7, Day 14 ]
    Area Under the Curve (AUC) of AGuIX

  4. Pharmacokinetic t1/2 of AGuIX [ Time Frame: Day 0 , Day 7, Day 14 ]
    pharmacokinetic term half-life (t1/2) of AGuIX

  5. distribution of AGuIX [ Time Frame: after the first and last injection of AGuIX, Week 0 and Day 14 ]
    measure of RMI contrast enhancement in tumor and healthy tissue

  6. Overall Survival [ Time Frame: from the start of treatment to death, up to 24 months ]
  7. Progression Free Survival (PFS) [ Time Frame: from the start of treatment to progression, up to 24 months ]
  8. Toxicity (CTCAE criteria) [ Time Frame: from baseline to 30 days after treatment (concomitant and adjuvant treatment) (week 35) ]
    according to NCI Common Toxicity Criteria for Adverse Effect (CTCAE) criteria



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04881032


Contacts
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Contact: Emilie Thivat 0473278089 emilie.THIVAT@clermont.unicancer.fr

Locations
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France
CHU de Brest
Brest, France
Centre Jean Perrin
Clermont-Ferrand, France, 63011
Principal Investigator: Julian Biau, MD         
CHU de Grenoble
Grenoble, France
Centre Léon Berard
Lyon, France
Institut de Cancérologie de l'Ouest
Saint Herblain, France
Institut de Cancérologie Strasbourg Europe
Strasbourg, France
Sponsors and Collaborators
Centre Jean Perrin
French Ministry of Health (PHRCI-19-060)
Investigators
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Principal Investigator: Juliette Moreau, Md Centre Jean Perrin
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Responsible Party: Centre Jean Perrin
ClinicalTrials.gov Identifier: NCT04881032    
Other Study ID Numbers: 2020-004552-15
First Posted: May 11, 2021    Key Record Dates
Last Update Posted: May 11, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents