The Sarah Nanotechnology System for Treatment of Advanced Metastatic Solid Tumors Using Hyperthermia.

This is a sequential, open-label, dose-escalation, non-randomized, prospective early feasibility clinical investigation designed to evaluate the safety of the Sarah Nanotechnology System, comprising intravenously administered Sarah Nanoparticles (SaNPs) in combination with a low-frequency Alternating Magnetic Field (AMF) generated by the Electromagnetic Induction System (EIS). The purpose of the study is to assess the safety profile of the SaNP and AMF combination and to identify the recommended dose and irradiation parameters for a subsequent feasibility study. The study will also provide initial information regarding device performance and efficacy. Scientific and Technical Background: The Sarah Nanotechnology System utilizes controlled magnetic hyperthermia to thermally damage malignant cells while sparing surrounding healthy tissue. Following a single intravenous administration, SaNPs, nanoparticles with iron oxide core, circulate systemically and preferentially accumulate within tumor tissue through the Enhanced Permeability and Retention (EPR) effect, then participant's upper torso is exposed to an AMF (≈ 290 ± 10% kHz) by the EIS (Electromagnetic Induced System). The obtained effect is heating at tumor site. Because AMF exposure can also induce eddy currents on the skin surface a patient cooling blanket system continuously helps regulating body surface temperature. Vital signs and skin temperature are monitored in real time throughout irradiation. Dose-Escalation Design: The study follows a standard 3 + 3 sequential escalation design, once the recommended dose is identified, an expansion cohort will repeat it. SaNP dose: 100% SaNP dose, calculated according to NOAEL. AMF parameters: 290 ± 10% kHz; total irradiation time up to 15 minutes in the first treatment cohort, increasing to 16-20 minutes at the next treatment cohort depending on safety review. Dose-limiting toxicity (DLT) criteria and escalation rules follow standard early-phase device study methodology. Treatment Procedure: On the treatment day, participants undergo laboratory tests and ECG assessment before SaNP infusion. Approximately four hours post-infusion, participants are positioned within the EIS coil for AMF irradiation while covered by a cooling blanket, and analgesic administration per physician discretion. Skin surface and oral temperatures, vital signs, and participant comfort are continuously monitored. After irradiation, repeat laboratory and ECG evaluations are performed prior to discharge. Follow-up assessments occur at 7 ± 2 days and 30 ± 5 days post-treatment and then every 3-6 months up to 5 years for long-term safety surveillance. Adverse events (AEs) and serious adverse events (SAEs) will be documented and evaluated for severity and relatedness to device or procedure. Real-time safety oversight is performed by the investigator and sponsor medical monitor; the DSMB periodically reviews cumulative safety data and recommends escalation, expansion, or study termination.