Effect of Electroacupuncture Combined With Paclitaxel Clinical Efficacy of Patients With Recurrence of High-grade Glioma

Official title

Specific Model Electroacupuncture Stimulation Promotes Paclitaxel Delivery Across the BBB for Postoperative Glioma Patients: A Randomized Controlled Study

Overview

Gliomas are the most common type of primary brain tumors, with surgery followed by radiotherapy and chemotherapy as the main treatment modalities. However, they are highly prone to recurrence, presenting significant treatment challenges, especially for high-grade gliomas, which have a 5-year survival rate of only 5.5%. Paclitaxel, a common chemotherapeutic agent, exhibits antitumor effects in vitro that are 1400 times stronger than those 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, precluding 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 blood-brain barrier, enhancing the concentration of albumin-bound paclitaxel (ABX) in tumor tissues, peritumoral tissues, and surrounding invasive tissues, thereby exerting antitumor effects. Consequently, this study aims to observe the safety and efficacy of SMES combined with ABX in treating patients with recurrent high-grade gliomas postoperatively, to explore its mechanisms of action, extend survival, improve quality of life, and forge new theories and methods for the integrative treatment of brain tumors combining traditional Chinese and Western medicine.

Interventions

• Drug Temozolomide（TMZ） injection or oral administration
  Oral administration of TMZ150-200mg/m2/ day, continuous use for 5 days, discontinued for 23 days, for a treatment cycle, a total of 6 cycles.
• Drug Albumin-Bound Paclitaxel(ABX) intravenous drip
  ABX was administered intravenously at a dose of 110mg/m2 on days 1 and 8 of a 28-day treatment cycle
• Device Specific mode electroacupuncture stimulation(SMES) intervention
  Patients take supine position. After skin disinfection with 75% ethanol routine disinfection, the stainless needle (size 0.25mm×40mm, Hua Tuo brand, Suzhou Medical Supplies Company Ltd in Jiangsu, China) will be inserted in GV20（Baihui) and the stainless needle(size 0.25mm×25mm, described above) will be inserted in GV26 (Shuigou), acupoints will be stimulated manually until patients feel soreness, distension or heaviness (the reaction of "De Qi"). Then, the needles are stimulated by using an acu

Primary outcome measures

• Overall survival（OS） [Time frame: Starting from randomization, during the follow-up phase, telephone follow-ups to record survival status are conducted every two months, totaling six follow-ups. This structured approach ensures a comprehensive assessment of patient out]

Secondary outcome measures (6)

• Progression-Free Survival (PFS) [Time frame: Up to 12 months were assessed from the date of randomization to the date of first recording to the date of progression or the date of death from any cause, whichever came first]
• Head MRI (plain and enhanced) [Time frame: One treatment cycle is 28 days, with cranial MRI scans conducted one day before the start of treatment cycles 1, 3, and 5, and at the end of treatment cycle 6.]
• he Karnofsky Performance Score (KPS) [Time frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.]
• The Eastern Cooperative Oncology Group (ECOG) [Time frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.]
• The Quality of Life (QOL) [Time frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.]
• The Neurological Assessment for Neuro-Oncology (NANO) [Time frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.]

Eligibility criteria

Inclusion criteria

• Histologically confirmed high-grade glioma, with standard radiotherapy and chemotherapy post-surgical resection deemed unsuccessful, and recurrence confirmed by imaging.
• Age ≥18 and ≤70 years, open to all genders.
• If receiving dexamethasone for mass effect, a stable daily dose of <6 mg in the 7 days prior to enrollment, or if the dose of dexamethasone is decreasing, an average daily dose of <6 mg in the 7 days prior to enrollment. Patients receiving dexamethasone for reasons other than mass effect are still eligible.
• A Karnofsky Performance Score (KPS) ≥70 or a World Health Organization (WHO) performance status of ≤2.
• Meets the criteria for acupuncture, with no severe complications, able to undergo acupuncture treatment and demonstrates good compliance.
• Clear consciousness, with the ability to perceive and distinguish pain, and capable of basic communication.
• Signed informed consent, voluntarily participating in this study.

Exclusion criteria

• Uncontrolled epileptic seizures;
• Peripheral neuropathy > Grade 1;
• Currently participating in another clinical trial or having participated in a clinical trial that concluded less than 3 months ago;
• Previous treatment with paclitaxel or similar chemotherapeutic or biologic agents, or history of allergic reactions to these compounds;
• Patients with severe cardiac, hepatic, renal, or hematologic dysfunction (criteria within 14 days prior to treatment include: a. Hemoglobin ≥ 90.0 g/L; b. White blood cells ≥ 3.010\^9/L; c. Absolute neutrophil count ≥ 1500/µL; d. Platelets ≥ 10010\^9/µL; e. Total bilirubin (TbIL) ≤5.0 x ULN; f. Serum aspartate aminotransferase (SGOT) ≤10 x ULN and TbIL >3 to ≤5.0 x ULN; g. Creatinine ≤1.5 mg/dL, estimated creatinine clearance ≥ 30 mL/min to <90 mL/min);
• Pregnant or breastfeeding women;
• Individuals with cognitive impairments such as congenital dementia, or with histories of alcohol, drug, or psychotropic substance abuse;
• Individuals with a history of needle fainting or infections at the site of acupuncture;
• Patients with conductive foreign bodies within the body;
• Individuals unable to undergo enhanced MRI examinations.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

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

Publications

• Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, Reifenberger G. Glioma. Nat Rev Dis Primers. 2015 Jul 16;1:15017. doi: 10.1038/nrdp.2015.17. PMID 27188790
• Rapp M, Baernreuther J, Turowski B, Steiger HJ, Sabel M, Kamp MA. Recurrence Pattern Analysis of Primary Glioblastoma. World Neurosurg. 2017 Jul;103:733-740. doi: 10.1016/j.wneu.2017.04.053. Epub 2017 Apr 19. PMID 28434963
• Wick W, Stupp R, Beule AC, Bromberg J, Wick A, Ernemann U, Platten M, Marosi C, Mason WP, van den Bent M, Weller M, Rorden C, Karnath HO; European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada Clinical Trials Group. A novel tool to analyze MRI recurrence patterns in glioblastoma. Neuro Oncol. 2008 Dec;10(6):1019-24. doi: 10.1215/15228517-2008-058. Ep PMID 18676355
• Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Insti PMID 19269895
• Dmello C, Sonabend A, Arrieta VA, Zhang DY, Kanojia D, Chen L, Gould A, Zhang J, Kang SJ, Winter J, Horbinski C, Amidei C, Gyorffy B, Cordero A, Chang CL, Castro B, Hsu P, Ahmed AU, Lesniak MS, Stupp R, Sonabend AM. Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma. Clin Cancer Res. 2022 Jul 15;28(14):3156-3169. doi: 1 PMID 35552677
• Aldape K, Brindle KM, Chesler L, Chopra R, Gajjar A, Gilbert MR, Gottardo N, Gutmann DH, Hargrave D, Holland EC, Jones DTW, Joyce JA, Kearns P, Kieran MW, Mellinghoff IK, Merchant M, Pfister SM, Pollard SM, Ramaswamy V, Rich JN, Robinson GW, Rowitch DH, Sampson JH, Taylor MD, Workman P, Gilbertson RJ. Challenges to curing primary brain tumours. Nat Rev Clin Oncol. 2019 Aug;16(8):509-520. doi: 10.1 PMID 30733593
• Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021 May;20(5):362-383. doi: 10.1038/s41573-021-00139-y. Epub 2021 Mar 1. PMID 33649582
• Parrish KE, Sarkaria JN, Elmquist WF. Improving drug delivery to primary and metastatic brain tumors: strategies to overcome the blood-brain barrier. Clin Pharmacol Ther. 2015 Apr;97(4):336-46. doi: 10.1002/cpt.71. Epub 2015 Feb 18. PMID 25669487

Identifiers

NCT: NCT06330337 · ZSLL-KY-2024-010-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗