Evaluation of Clinical Efficacy and Safety of Specific Mode Electroacupuncture Stimulation for Paclitaxel Across BBB Delivery in Patients With Postoperative Recurrence of Malignant Glioma: A Single-arm Trial

Обзор

Gliomas are the most common type of primary brain tumors, with the main treatment modalities including surgery, radiotherapy, and chemotherapy. However, gliomas are highly prone to recurrence, posing significant treatment challenges, especially for high-grade gliomas, which have a 5-year survival rate of only 5.5%. Paclitaxel (PTX) is a common chemotherapeutic agent, and its in vitro antitumor efficacy is 1400 times stronger than that of temozolomide (the first-line chemotherapy drug for gliomas). However, due to its large molecular weight (approximately 893 Da), it cannot cross the blood-brain barrier (BBB), preventing its use as a first-line treatment for gliomas. Preliminary research by our team has demonstrated that Specific Mode Electroacupuncture Stimulation (SMES) can open the BBB, increasing the concentration of PTX in tumor tissues, peritumoral tissues, and surrounding invasive tissues, thereby exerting antitumor effects. Therefore, this study aims to preliminarily observe the safety and efficacy of SMES combined with PTX in treating patients with postoperative recurrent high-grade gliomas.

Вмешательства

• Другое SMES+PTX
  This intervention involves the combined use of medication and device, where the specific mode electroacupuncture stimulation (SMES) intervention is administered simultaneously with the intravenous infusion of paclitaxel.
• Препарат Paclitaxel
  Paclitaxel is administered intravenously at a dose of 135-175mg/m², repeated every 3 weeks.
• Устройство Specific mode electroacupuncture stimulation
  Patients assume a supine position. After routine skin disinfection with 75% ethanol, a stainless steel needle (size 0.25mm×40mm) is inserted into GV20 (Baihui), and another stainless steel needle (size 0.25mm×25mm, as described above) is inserted into GV26 (Shuigou). The acupoints are manually stimulated until the patient experiences soreness, distension, or heaviness (the "De Qi" response). Subsequently, the needles are stimulated using an acupuncture point nerve stimulator (HANS-200, Nanjing J

Первичные конечные точки

• 4-month progression-free survival rate [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.]

Вторичные конечные точки (9)

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.]
• The Neurological Assessment for Neuro-Oncology (NANO) [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.]
• Overall survival(OS) [Срок оценки: On the last day of weeks 3, 6, 9, 12, 15, and 18 during the treatment period; and then monthly during the follow-up phase for a total of 12 times.]
• Disease control rate [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.]
• Objective response rate [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.]
• Progression-free survival [Срок оценки: On the last day of weeks 3, 6, 9, 12, 15, and 18 during the treatment period; and then monthly during the follow-up phase for a total of 12 times.]
• Duration of response [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18]
• Duration of Disease Control [Срок оценки: baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18]
• Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Срок оценки: On the 7th, 14th and 21st days of the 1st to 6th treatment cycles, each treatment cycle lasts for 21 days.]

Критерии участия

Критерии включения

• WHO grade IV glioma as defined in the "Integrated Diagnosis and Treatment Guidelines for Glioma of the Chinese Anti-Cancer Association" (V2.0\_2025 (20250110)).
• Recurrence confirmed by cranial MRI after surgical resection.
• According to the Response Assessment in Neuro-Oncology Criteria, version 2.0 (RANO 2.0) standards, there is at least one measurable lesion.
• Age ≥ 18 years and ≤ 70 years, gender not limited.
• If dexamethasone is used due to the space-occupying effect, the stable daily dose within 7 days before enrollment should be < 6 mg; if the dose of dexamethasone is being reduced, the average daily dose within 7 days before enrollment should be < 6 mg. Patients receiving dexamethasone treatment for reasons other than the space-occupying effect can still be enrolled.
• Karnofsky Performance Status Score (KPS) ≥ 40 points or World Health Organization (WHO) Performance Status Score ≤ 3 points.
• Good bone marrow function, liver and kidney function (within 14 days before treatment): a. Hemoglobin ≥ 90.0 g/L; b. White blood cells ≥ 3.0\*10\^9/L; c. Absolute neutrophil count ≥ 1500/µL (white blood cell count \* neutrophil percentage); d. Platelets ≥ 100\*10\^9/µl; e. Total bilirubin (TbIL) ≤ 5.0 x ULN; f. Serum aspartate aminotransferase (SGOT) ≤ 3 x ULN and TbIL ≤ 3.0 x ULN; g. Creatinine ≤ 1.5 mg/dL, estimated glomerular filtration rate ≥ 30 mL/min to < 90 mL/min)
• Able to receive electroacupuncture treatment and have good compliance.
• Clear consciousness, pain perception and discrimination ability, and basic communication ability.
• Signed the informed consent form and voluntarily participated in this study.

Критерии исключения

• Seizure attack, uncontrollable.
• Those who are currently participating in other clinical trials or have completed other clinical trials within less than one month.
• Those who have received treatment containing paclitaxel or similar drugs.
• Those who have a severe allergy to paclitaxel or similar substances.
• Pregnant or lactating women.
• Those with diseases affecting cognitive function such as congenital dementia, or alcoholics, drug addicts or those with abuse of psychotropic substances.
• Those with infected skin at the acupuncture site.
• Patients with metallic foreign bodies in their bodies.
• Those who cannot undergo cranial enhanced MRI examination.
• Other acute or chronic diseases, mental disorders or abnormal laboratory test values that may increase the risk associated with participating in the study or the administration of the study drug, or interfere with the interpretation of study results, and the investigator determines that the patient does not meet the eligibility criteria for participation in the study.
• Those who are undergoing other types of anti-tumor treatments simultaneously during the trial, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Third Affiliated Hospital of Zhejiang Chinese Medical University — China

Публикации

• Chamberlain MC, Kormanik P. Salvage chemotherapy with paclitaxel for recurrent primary brain tumors. J Clin Oncol. 1995 Aug;13(8):2066-71. doi: 10.1200/JCO.1995.13.8.2066. PMID 7636549
• Chang SM, Kuhn JG, Robins HI, Schold SC Jr, Spence AM, Berger MS, Mehta M, Pollack IF, Rankin C, Prados MD. A Phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants: a North American Brain Tumor Consortium report. Cancer. 2001 Jan 15;91(2):417-22. doi: 10.1002/1097-0142(20010115)91:23.0.co;2-9. PMID 11180089
• Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, Meltzer J, Korejwa A, Jane-Valbuena J, Mapa FA, Thibault J, Bric-Furlong E, Raman P, Shipway A, Engels IH, Cheng J, Yu GK, Yu J, Aspesi P Jr, de Silva M, Jagtap K, Jones MD, Wang L, Hatton C, Palescandolo E, Gupta S, Mahan S, S PMID 22460905
• Caffery B, Lee JS, Alexander-Bryant AA. Vectors for Glioblastoma Gene Therapy: Viral & Non-Viral Delivery Strategies. Nanomaterials (Basel). 2019 Jan 16;9(1):105. doi: 10.3390/nano9010105. PMID 30654536
• Zhang S, Gong P, Zhang J, Mao X, Zhao Y, Wang H, Gan L, Lin X. Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes. Front Neurosci. 2020 Oct 6;14:582324. doi: 10.3389/fnins.2020.582324. eCollection 2020. PMID 33122995
• Park J, Aryal M, Vykhodtseva N, Zhang YZ, McDannold N. Evaluation of permeability, doxorubicin delivery, and drug retention in a rat brain tumor model after ultrasound-induced blood-tumor barrier disruption. J Control Release. 2017 Mar 28;250:77-85. doi: 10.1016/j.jconrel.2016.10.011. Epub 2016 Oct 11. PMID 27742444
• Siegal T, Rubinstein R, Bokstein F, Schwartz A, Lossos A, Shalom E, Chisin R, Gomori JM. In vivo assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans. J Neurosurg. 2000 Apr;92(4):599-605. doi: 10.3171/jns.2000.92.4.0599. PMID 10761648
• Graham-Gurysh EG, Murthy AB, Moore KM, Hingtgen SD, Bachelder EM, Ainslie KM. Synergistic drug combinations for a precision medicine approach to interstitial glioblastoma therapy. J Control Release. 2020 Jul 10;323:282-292. doi: 10.1016/j.jconrel.2020.04.028. Epub 2020 Apr 23. PMID 32335153

Идентификаторы

NCT: NCT06818331 · ZSLL-KY-2024-079-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗