In short
Gadolinium-chelated polysiloxane nanoparticles are an investigational substance being studied to improve radiotherapy for glioma, a type of brain cancer. One clinical trial is currently authorised, a Phase 1/2 study in 66 participants with newly diagnosed glioblastoma. The substance has received orphan designation from the European Medicines Agency for the treatment of glioma.
Key points
- Phase 1/2 trial in newly diagnosed glioblastoma, with 66 planned participants
- The trial is currently authorised but not yet recruiting
- The substance is given intravenously alongside radiotherapy and temozolomide chemotherapy
- Phase I measures the recommended dose based on dose-limiting toxicities
- Phase II measures the 6-month progression-free survival rate
- The substance received orphan designation for glioma from the EMA in January 2022
Contents
- What is gadolinium-chelated polysiloxane nanoparticles?
- How does gadolinium-chelated polysiloxane nanoparticles work?
- Which conditions is it used or studied for?
- How is gadolinium-chelated polysiloxane nanoparticles given?
- What do the clinical trials show?
- What side effects are known?
What is gadolinium-chelated polysiloxane nanoparticles?
Gadolinium-chelated polysiloxane nanoparticles are an investigational substance containing a metal called gadolinium attached to nanoparticles. The substance is not an authorised medicine; it was designated as an orphan medicine for the treatment of glioma in the European Union on 14 January 2022, which means the developer receives scientific and regulatory support from the European Medicines Agency (EMA) but the medicine is not yet available for use outside clinical trials. In the trial registry, the substance appears under the name AGuIX.
How does gadolinium-chelated polysiloxane nanoparticles work?
The medicine contains gadolinium, a metal, attached to nanoparticles. These metallic nanoparticles are expected to enter cancer cells and help the tumour absorb more radiation during radiotherapy. They are also expected to cause the formation of very reactive chemicals called reactive oxygen species, which can further damage the cancer cells. This combined effect is expected to slow down the progression of the disease.
Which conditions is it used or studied for?
- Glioma — a type of brain cancer for which treatment includes radiotherapy; the substance received orphan designation for this condition.
- Newly diagnosed glioblastoma — an aggressive form of brain cancer; the authorised clinical trial is studying the substance in this specific condition.
How is gadolinium-chelated polysiloxane nanoparticles given?
The substance is given by intravenous administration, meaning it is injected directly into a vein. In the clinical trial, it is given in combination with radiotherapy and temozolomide, a chemotherapy medicine, during the concomitant radiochemotherapy period.
What do the clinical trials show?
One clinical trial is currently authorised for this substance. It is a Phase 1/2 study with a planned enrolment of 66 participants with newly diagnosed glioblastoma. The trial investigates AGuIX nanoparticles given together with radiotherapy and concomitant temozolomide.
The study is divided into two parts. Phase I aims to determine the recommended dose of AGuIX in combination with radiotherapy and temozolomide during the concomitant radiochemotherapy period. The recommended dose is defined as the highest dose tested in which the percentage of dose-limiting toxicities is less than 33%; a dose-limiting toxicity is defined as any grade 3–4 toxicity, except alopecia, nausea, and vomiting, occurring during the first 6 weeks. Phase II aims to estimate the efficacy of the combination radiochemotherapy plus AGuIX at the recommended dose, measured by the 6-month progression-free survival rate using RANO criteria. Progression-free survival means the length of time a participant lives without the cancer getting worse.
At the time of the orphan designation application, the effects of the medicine had been evaluated in experimental models, and clinical trials with the medicine in patients with glioma were ongoing.
What side effects are known?
The supplementary source does not report specific side effects of gadolinium-chelated polysiloxane nanoparticles. The clinical trial will collect information on dose-limiting toxicities, defined as any grade 3–4 toxicity except alopecia, nausea, and vomiting, during the first 6 weeks of treatment.