Researchers are launching a randomized phase II clinical trial that will test whether an investigational nanoparticle can make whole-brain radiation therapy more effective for patients whose cancer has spread to the brain in multiple locations. The study, known as NANORAD 2, is described in a study protocol published in BMC Cancer, and it is registered with ClinicalTrials.gov under identifier NCT03818386.
Multiple brain metastases represent a critical stage in the progression of many cancers, carrying significant consequences for neurological function and overall survival, even in an era that includes new targeted therapies and stereotactic radiotherapy. For patients whose disease pattern rules out focused stereotactic treatment, whole-brain radiation therapy (WBRT) remains an important option, which is why the trial’s investigators argue that agents capable of increasing the efficiency of this treatment deserve systematic exploration.
The nanoparticle at the center of the trial, AGuIX, is described in the protocol as a theranostic and radiosensitizing agent. According to the published background, AGuIX nanoparticles have demonstrated effectiveness in preclinical studies and are currently being evaluated in ongoing clinical trials. The first-in-human phase 1 NANO-RAD study showed good tolerance of intravenous injection of AGuIX at doses up to 100 mg/kg, the dose selected for the new trial, and demonstrated selective uptake of the particles in tumors as visualized by MRI.
NANORAD 2 is designed as a multicentric, prospective, randomized, open-label, blinded-endpoint phase II clinical trial. Eligible patients are those with multiple brain metastases from a histologically confirmed solid tumor who could not benefit from stereotactic radiotherapy. Randomization will be carried out centrally using a minimization procedure, a method intended to balance potential prognostic factors between the two treatment groups rather than relying on simple chance alone.
Participants will be assigned to receive either WBRT alone or WBRT combined with AGuIX. The radiation prescription in the trial is 30 Gy delivered in 10 fractions of 3 Gy. In the combination arm, patients will receive three intravenous injections of AGuIX at 100 mg/kg. The protocol specifies that the study will be adaptive, with an interim analysis planned after the enrollment of 20 patients who have received at least one injection or radiotherapy in each arm of treatment.
The primary objective of the trial is to determine the best objective intracranial response rate, assessed at two time points: 6 weeks and 3 months. Because this is a study protocol, the published article reports the planned design and objectives rather than results; no efficacy findings from NANORAD 2 are available in the source material, and any conclusions about whether AGuIX improves outcomes must await the trial’s data.
In the discussion section of the protocol, the authors note that the persistent role of WBRT in treating multiple brain metastases, and its association with innovative techniques including hippocampal avoidance, justifies exploring agents that increase the efficiency of this treatment. They state that NANORAD 2 is the first randomized clinical trial using intravenous AGuIX nanoparticles as a radiosensitizer, and that the study will evaluate whether AGuIX increases local control in combination with WBRT.
The trial carries regulatory identifiers beyond its ClinicalTrials.gov registration: it holds an identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM) under Eudra CT number 2018-001879-20, and the protocol described is version 9, dated 10 May 2023. The article was published open access on 23 October 2026 and is shared as an early, citable version subject to further edits before the final Version of Record.
According to the protocol’s discussion, expected positive clinical outcomes from the study would support the value of AGuIX as a treatment option in a subtype of patients with important unmet medical needs. Until those outcomes are reported, the trial stands as a planned test of whether tumor-targeted nanoparticles can safely amplify the effect of a long-standing radiotherapy technique for one of the most difficult stages of cancer progression.
Subject of Research: A randomized phase II trial protocol testing AGuIX nanoparticles as radiosensitizers combined with whole-brain radiotherapy for multiple brain metastases.
Article Title: Radiotherapy of multiple brain metastases using AGuIX nanoparticles: a prospective randomized phase II study protocol
Article References: Mercier, A., Villa, J., Bellier, A., Jover, F., Gataleta, M., Le Costaouec, T., Grasso, L., Leboucher, A., Giraud, J.-Y., Gavard, M., Tillement, O., Dufort, S., De Beaumont, O., Le Duc, G., & Verry, C. (2026). Radiotherapy of multiple brain metastases using AGuIX nanoparticles: a prospective randomized phase II study protocol. BMC Cancer. https://doi.org/10.1186/s12885-026-17173-x
Image Credits: AI Generated
DOI: 10.1186/s12885-026-17173-x
Keywords: AGuIX nanoparticles, brain metastases, whole-brain radiation therapy, radiosensitizer, phase II trial, NANORAD 2, clinical trial protocol, theranostics, MRI tumor uptake, WBRT, oncology, Radiotherapy
News Source: Nathaniel Bowman. (October 29, 2026). Nanoparticle radiosensitizer to be tested with whole-brain radiotherapy in new phase II trial. Scienmag.
