First-in-Human Safety and Efficacy Study on Combination of High-Intensity Focused Ultrasound Sonication and Micellar Nanoparticle-Encapsulated Epirubicin, K-912: A Novel Sonodynamic Therapy for the Treatment of Refractory Abdominal Cancers.

[OBJECTIVE] Aims of this first-in-human clinical trial were to evaluate the safety and efficacy of sonodynamic therapy (SDT) using a newly developed trigger pulse high-intensity focused ultrasound (HIFU) device, MS-2, and micellar nanoparticle-encapsulated epirubicin, K-912, in patients with unresectable refractory abdominal cancers.

[METHODS] This was a single center prospective exploratory clinical trial. The HIFU sonication power (75 and 150 W at 1 MHz) and K-912 dose (30 and 80 mg/m) were increased incrementally (4 cohorts) according to 3+3 design. Each cohort consisted of three patients. K-912 was administered intravenously one day before HIFU treatment.

[RESULTS] A total of 12 patients with stage IV pancreatic cancer (n = 11) and cholangiocellular carcinoma (n = 1) completed the SDT. The mean sonication time and total number of sonication was 22.3 min and 17.4 shots, respectively. No adverse events of grade ≥3 were observed during the trial up to 30 days after HIFU treatment. No adverse events related to K-912 were noted. The HIFU sonication power and K-912 dose considered to be tolerable were 150 W and 80 mg/m, respectively. The rate of complete and partial tumor coagulative necrosis was 33.3% and 41.7%, respectively. The primary disease control rate was 66.7%. Pain was improved in 33.3% of patients.

[CONCLUSIONS] This trial demonstrated that SDT using MS-2 and K-912 was safe and well tolerated in patients with advanced abdominal tumors and showed promising preliminary clinical activity.