Etude Clinique de Phase I de Radiosensibilisation de métastases cérébrales Par Nanoparticules de Gadolinium
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Maximum-tolerated dose (MTD) of polysiloxane gadolinium-chelates based nanoparticles (AGuIX) given concurrently to the whole brain radiation therapy for the treatment of multiple brain metastases
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: AGuIX (Drug)
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
Intervention: whole brain radiation therapy (Radiation)
Outcomes
Primary Outcomes
Maximum-tolerated dose (MTD) of polysiloxane gadolinium-chelates based nanoparticles (AGuIX) given concurrently to the whole brain radiation therapy for the treatment of multiple brain metastases
Time Frame: 18 months
To determine Maximum-tolerated dose (MTD) of polysiloxane gadolinium-chelates based nanoparticles (AGuIX) given concurrently to the whole brain radiation therapy, according to incidence of dose limiting toxicity (DLT) graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Secondary Outcomes
- Distribution of AGuIX particles in brain metastases and surrounding healthy tissue evaluated by MRI(30 months)
- Pharmacokinetic characteristics of AGuIX particles after intravenous injection(18 months)
- Overall survival(30 months)
- Intracranial progression-free survival(12 months after radiation)