evaluating aguix® nanoparticles in combination with stereotactic radiation for brain metastases

Conditions: Brain Metastases

Summary: this study evaluates the clinical impact of aguix® nanoparticles in combination with fractionated stereotactic radiation in oligo brain metastases.

aguix® (activation and guidance of irradiation by x-ray, nh theraguix) are gadolinium chelated polysiloxane based nanoparticles with magnetic resonance contrast properties, able to accumulate in the tumor through the enhanced permeability and retention effect and sufficiently small (sub-5 nm diameter) to allow for renal clearance. aguix® nanomedicine can be used as: * positive contrast agent for magnetic resonance imaging (mri). it displays higher efficacy than commercial contrast agents and so it can be used to delineate precisely the tumors. * a booster of radiotherapy during the radiotherapy protocol, after the localization of the tumor. this is permitted by the high radiosensitizing potential of aguix® that allows a local increase of efficacy of x-ray damages. french and international groups have demonstrated the radiosensitizer effect of aguix® to improve the efficacy of radiotherapy. thanks to a difference in porosity between the vascular networks, aguix® penetrates and resides in tumor tissues, but not in healthy tissues.

Eligibility criteria:
inclusion criteria: * male or female patients aged of at least 18 years on day of signing informed consent. * histologically-confirmed diagnosis of any histological type of solid tumors, excluding primary central nervous system (cns) tumors. * radiological evidence by mri : at least one and a maximum of 5 brain metastases, and at least one brain lesion with a longest diameter ≥ 2 cm and eligible for fsrt. * patient without progression on extracranial disease documented by radiological assessment as per recist v1.1 within 4 weeks before inclusion. * for patients treated with a systemic anti-cancer therapy: a minimal 2-week washout period is required from the date of last systemic treatment administration to day 1, except for hormonal agents. * ecog performance status (ps) ≤2. * absolute neutrophil count (anc) ≥ 1.0 g/l, platelets ≥ 75 g/l, hemoglobin ≥ 8 g/dl, serum creatinine or creatinine clearance according to ckd-epi ≤ 1.5 x upper limit of normal (uln) or ≥ 50 ml/min/1.73m2, asat and alat ≤ 3 x uln (or ≤ 5.0 uln in case of liver metastasis or hepatic infiltration),inr and activated partial thromboplastin time (aptt) ≤1.5 x uln. * women of child-bearing potential must have a negative serum pregnancy test at screening and must agree to use 2 effective forms of contraception from the time of the negative pregnancy test up to 3 months after the last dose of the study drug. * fertile men must agree to use contraceptive measures up to 3 months after the last dose of study drug. * patients who understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures. patient should be able and willing to comply with study visits and procedures as per protocol. * patients must be covered by a medical insurance. exclusion criteria: * prior local treatment with radiotherapy (whole / partial brain or stereotactic radiosurgery) or surgical resection of brain lesions. * patient participating to another clinical trial with an investigational agent. * patients who have not recovered from significant adverse events (i.e. grade \> 2 ae according to nci ctcae v5.0) due to prior treatment with anti-cancer agents with exception of any grade alopecia or lab values presented in inclusion criteria. * contra-indication for mri enhanced with gadolinium (e.g. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements, certain metal implants). * patients who are pregnant or breastfeeding.

Keywords: stereotactic radiation nanoparticles