Clinical Efficacy and Safety Assessment of Specific-Mode Electroacupuncture Stimulation Combined With Paclitaxel for Recurrent Malignant Gliomas: Study Protocol for a Single-Arm Trial

TL;DR

This study will test if combining a specific electrical stimulation with a chemotherapy drug improves outcomes for patients with recurring brain tumors.

Contribution

The novel approach combines specific-mode electroacupuncture stimulation with paclitaxel to potentially overcome the blood-brain barrier in glioma treatment.

Findings

The trial will assess safety and 4-month progression-free survival in patients with recurrent malignant gliomas.

The study will provide data to support future large-scale clinical trials of SMES+ABX therapy.

Patient-reported quality of life and survival outcomes will be evaluated over a 28-month period.

Abstract

Despite advances in surgical resection, radiotherapy, and chemotherapy, the prognosis of recurrent malignant gliomas (rMG) remains poor, with limited efficacy of conventional treatments due to the blood-brain barrier (BBB) hindering drug delivery to the tumor site. Studies have demonstrated that albumin-bound paclitaxel (ABX), while potent in vitro, is restricted in its intravenous use due to BBB limitations. To overcome this, specific-mode electrical stimulation (SMES) has shown promise in transiently opening the BBB, enhancing the accumulation of ABX in glioma tumors. Therefore, this protocol designs a single-center, single-arm, prospective phase II clinical trial aiming to evaluate the safety and clinical efficacy of SMES combined with ABX (SMES+ABX) for treating rMG.

This study primarily evaluates the safety of SMES+ABX therapy in treating patients with rMG and assesses whether it can improve the 4-month progression-free survival (4m-PFS) rate, while providing data support for future large-scale clinical trials.

In this study, 20 eligible patients will receive intravenous ABX (135‐175 mg/m²) per 21-day cycle for 6 cycles, combined with SMES for BBB modulation. A Simon 2-stage design will be employed, with the primary end point being the 4m-PFS. Secondary end points include adverse events, disease control rate, objective response rate, duration of disease control, duration of response, Neurological Assessment in Neuro-Oncology score, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, progression-free survival, and overall survival.

The results will determine the 4m-PFS rate, overall safety profile, secondary efficacy outcomes, and patient-reported quality of life measures. The data will be analyzed upon trial completion. Patient enrollment is scheduled to begin in May 2025. The treatment and primary efficacy assessment phases are anticipated to be completed by January 2027 (allowing for staggered enrollment and a 4-month treatment period for the last enrolled patient). The final survival follow-up for all patients is anticipated to be completed by January 2028 (ie, 1 year after the last patient completes treatment). Data management is currently ongoing, and formal statistical analyses have not yet been performed.

This study aims to evaluate the efficacy and safety of SMES combined with ABX in the treatment of rMG. If successful, the combination could offer a promising therapeutic strategy for this challenging patient population.

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