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

NCT06330337 | Recruiting Phase 3

• 1 other identifier: ZSLL-KY-2024-010-01
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioma

Keywords

glioma; Specific Mode Electroacupuncture Stimulation; protein-bound paclitaxel; blood-brain barrier

Outcome Measures

Primary Outcomes (1)

• Overall survival（OS）

  The duration from randomization to death due to any cause is measured (for patients lost to follow-up, the last follow-up date is used; for patients alive at the end of the study, the date of the last follow-up is considered).

  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 Outcomes (6)

• Progression-Free Survival (PFS)

  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)

  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)

  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)

  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)

  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.

Study Arms (2)

TMZ group

OTHER

Temozolomide（TMZ） was given orally or intravenously 150mg/(m2·d) for 5 days, repeated every 28 days for 6 cycles

Drug: Temozolomide（TMZ） injection or oral administration

SMES+ABX+TMZ Group

OTHER

Drug: Oral or intravenous infusion of TMZ 150mg/(m2·d) for 5 days, repeated after 23 days of suspension, a total of 6 treatment cycles. During the TMZ treatment cycle, specific mode electroacupuncture stimulation（SMES） combined with Paclitaxel for Injection (Albumin Bound)（ABX） were used on day 1 and day 8. ABX： ABX was prepared with 0.9% sodium chloride injection and the dosage required by the patient was calculated at 110mg/mm2. Then the intravenous infusion continues for 30 minutes. SMES：Immediately after the ABX intravenous infusion began, the patient was placed in a supine position, the skin was routinely disinfected with 75% ethanol, and a stainless steel needle was inserted into GV20 and GV26.Then, the needles are stimulated by using an acupuncture point nerve stimulator with a frequency of 2/100 Hz and an intensity of 3 mA for 40 min (a homemade relay cycled power to the electrode for 6 sec on and 6 sec off).

Drug: Temozolomide（TMZ） injection or oral administration; Drug: Albumin-Bound Paclitaxel(ABX) intravenous drip; Device: Specific mode electroacupuncture stimulation(SMES) intervention

Interventions

Temozolomide（TMZ） injection or oral administration DRUG

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.

SMES+ABX+TMZ Group; TMZ group

Albumin-Bound Paclitaxel(ABX) intravenous drip DRUG

ABX was administered intravenously at a dose of 110mg/m2 on days 1 and 8 of a 28-day treatment cycle

SMES+ABX+TMZ Group

Specific mode electroacupuncture stimulation(SMES) intervention DEVICE

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 acupuncture point nerve stimulator (HANS-200, Nanjing Jinsheng, Ltd., China) with a frequency of 2/100 Hz and an intensity of 3 mA for 40 min (a homemade relay cycled power to the electrode for 6 sec on and 6 sec off).The 28-day treatment cycle was followed by simultaneous intervention with ABX on days 1 and 8.

SMES+ABX+TMZ Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Third Affiliated hospital of Zhejiang Chinese Medical University: lead
• Zhejiang University: collaborator

Study Sites (1)

The Third Affiliated Hospital of Zhejiang Chinese Medical University

Zhejiang, China

RECRUITING

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MeSH Terms

Conditions

Glioma

Interventions

Administration, Oral; Infusions, Intravenous; Methods

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Administration, Intravenous; Infusions, Parenteral; Investigative Techniques

Central Study Contacts

Xianming Lin, PHD

CONTACT

+86-13858028101; linxianming1966@163.com

Zhaoxing Jia, PHD

CONTACT

+86-18356130598; zhenxinzhenyi183@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 26, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)