Clinical efficacy and safety assessment of specific model electroacupuncture stimulation in enhancing paclitaxel delivery across the blood-brain barrier for recurrent malignant glioma: study protocol of a single-arm trial

IntroductionDespite advances in surgical techniques, radiotherapy, and chemotherapy, the prognosis for patients with recurrent malignant gliomas remains poor. Although paclitaxel is widely used for peripheral solid tumors and demonstrates potent antitumor effects in glioma cell lines in vitro, its clinical efficacy against recurrent malignant gliomas via intravenous administration remains suboptimal due to blood-brain barrier (BBB) restrictions. Recent studies have demonstrated that specific-mode electrical stimulation (SMES) can transiently open the BBB, thereby enhancing tumor accumulation of albumin-bound paclitaxel (ABX) and exerting anti-glioma effects. This study aims to evaluate the therapeutic efficacy and safety profile of SMES combined with ABX in patients with recurrent malignant gliomas. Methods and analysisThis is a single-center, single-arm, prospective phase II clinical trial. A total of 20 patients with histologically confirmed recurrent malignant gliomas (WHO grade 4) will be enrolled. Eligible patients will receive intravenous ABX (135-175 mg/m{superscript 2}) every 21 days for a total of 6 cycles. A Simons two-stage design will be employed, with the primary endpoint being the 4-month progression-free survival (PFS) rate. Secondary endpoints include adverse events (AEs), disease control rate (DCR), objective response rate (ORR), duration of disease control (DDC), duration of response (DOR), Neurological Assessment in Neuro-Oncology (NANO) score, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), progression-free survival (PFS), and overall survival (OS). Ethics and disseminationThis study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhejiang Chinese Medical University. The study findings will be presented at international conferences and published in peer-reviewed journals. Trial registration numberNCT06818331 STRENGTHS AND LIMITATIONS OF THIS STUDY{Rightarrow} This study explores potential therapeutic options for refractory diseases characterized by the absence of effective standard therapies and short survival expectancy. {Rightarrow}A key strength of this trial lies in its ability to yield rapid results, thereby optimizing resource allocation. {Rightarrow}Comparable clinical data demonstrate that the safety profile of this regimen is predictable, acceptable, and manageable. {Rightarrow}The primary limitation involves the single-arm design, wherein comparison with external historical controls may introduce bias and compromise the strength of conclusions. {Rightarrow}The modest sample size may result in insufficient statistical power for secondary endpoint analyses. {Rightarrow}Despite standardized assessment protocols, the intrinsic heterogeneity of neuro-oncological malignancies may affect the consistency of therapeutic response evaluations.