Radiosensitization of Multiple Brain Metastases Using AGuIX Gadolinium Based Nanoparticles

NCT ID: NCT02820454

Last Updated: 2019-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-02-28

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. AGuIX particles may increase the effectiveness of radiation therapy by making tumor cells more sensitive to radiation.

PURPOSE: This first-in-man Phase I trial will study the side effects and best dose of AGuIX when injected together with whole brain radiation therapy in treating patients with multiple brain metastases. The effectiveness of the combination of AGuIX and radiation therapy will be also assessed.

Detailed Description

The present study will investigate the safety, tolerability and spectrum of side effects of AGuIX in combination with whole brain radiation therapy. As such, this study will characterize the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of in combination with whole brain radiation therapy in patients with multiple brain metastases.

On day 1, patients will receive a single intravenous injection of AGuIX. An MRI scan will be performed 2 hours after injection to visualize the distribution of AGuIX in brain metastases and surrounding healthy tissue, and to evaluate the contrast enhancement in brain metastases. Then patients will undergo a whole brain radiation therapy, starting 4 hours after AGuIX injection, up to completion of 2 weeks, 5 days a week of treatment (30Gy, 3Gy/fraction).

During the first 24h after injection, several blood draws will be also performed in order to assess the pharmacokinetic of AGuIX.

After completion of study treatment, patients will be followed periodically.

Patients will be enrolled in cohorts and will be treated at sequentially rising dose levels of AGuIX combined with whole brain radiation therapy. Three subjects will initially enter at each dose. If none of the three experiences a dose-limiting toxicity we will proceed to the next dose. If one of the three experiences that level of toxicity, we will accrue 3 more subjects at that dose. If at any time there are two or more dose-limiting toxicities (in the 3-6 subjects) on a given dose, we will drop down to a lower dose. Dose escalation will continue until the MTD of AGuIX and whole brain radiation therapy is established. The MTD will then be one dose below the DLT occurring in at least 1 out of 3 subjects (2 out of 6 patients).

Conditions

Brain Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AGuIX and radiotherapy

Patients receive a single intravenous injection of AGuIX on day 1. Then patients undergo a whole brain radiation therapy, 5 days a week in weeks 1-2. The first radiotherapy session will be performed 4 hours after AGuIX injection.

Five dose escalation cohorts : 15 mg/kg, 30mg/kg, 50mg/kg, 75mg/kg and 100 mg/kg

Group Type: EXPERIMENTAL

AGuIX

Intervention Type: DRUG

A single intravenous injection on day 1. Dose level 1: 15mg/kg; Dose level 2: 30mg/kg, Dose level 3: 50mg/kg; Dose level 4: 75mg/kg; Dose level 5: 100mg/kg

whole brain radiation therapy

Intervention Type: RADIATION

30Gy in 10 sessions of 3Gy (5 days a week in weeks 1-2); first session 4 hours after AGuIX injection.

Interventions

AGuIX

A single intravenous injection on day 1. Dose level 1: 15mg/kg; Dose level 2: 30mg/kg, Dose level 3: 50mg/kg; Dose level 4: 75mg/kg; Dose level 5: 100mg/kg

Intervention Type: DRUG

whole brain radiation therapy

30Gy in 10 sessions of 3Gy (5 days a week in weeks 1-2); first session 4 hours after AGuIX injection.

Intervention Type: RADIATION

Other Intervention Names

Nano-sized gadolinium particles

Eligibility Criteria

Inclusion Criteria

• Patients with brain metastasis ineligible for local treatment by surgery or stereotactic radiation
• At least 18 years old
• Secondary brain metastases from a histologically confirmed solid tumor
• Patient competent to give informed consent (ou Signed informed consent after informing the patient)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
• No prior brain irradiation
• No renal insufficiency (glomerular filtration rate > 60 mL/min/1.73m²)
• Normal liver function (bilirubin < 30 µmol/L; Alkaline phosphatase < 400 UI/L; Aspartate aminotransferase (AST) < 75 UI/L; Alanine aminotransferase (ALT) < 175 UI/L)
• For both male and female patients, effective methods of contraception must be used throughout the study. Acceptable methods of contraception are oral or implantable contraceptives, intrauterine device, condoms, spermicidal gels, or surgical sterilization.
• Affiliated to a social security scheme or assimilated

Exclusion Criteria

• Meningeal carcinomatosis
• Progressive and threatening extracranial disease
• Previous cranial irradiation (whether whole or partial brain radiation therapy, except stereotactic irradiation) or total body irradiation
• Known contra-indication, sensitivity or allergy to gadolinium
• Patients unable to undergo or tolerate Magnetic Resonance Imaging
• Patients participating in another clinical investigation at the time
• Protected persons under articles L1121-5 to L1121-8, Code of Public Health

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NH TherAguix SAS

OTHER

Sponsor Role: collaborator

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Camille VERRY, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

University Hospital Grenoble

Grenoble, , France

Countries

France

References

Verry C, Sancey L, Dufort S, Le Duc G, Mendoza C, Lux F, Grand S, Arnaud J, Quesada JL, Villa J, Tillement O, Balosso J. Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol. BMJ Open. 2019 Feb 11;9(2):e023591. doi: 10.1136/bmjopen-2018-023591.

Reference Type: DERIVED

PMID: 30755445 (View on PubMed)

Other Identifiers

2015-004259-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

38RC15.278

Identifier Type: -

Identifier Source: org_study_id