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

Phase 3

Recruiting

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

• Registration Number: NCT06330337
• Lead Sponsor: The Third Affiliated hospital of Zhejiang Chinese Medical University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-02-26
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-19
• Last Update Submitted: 2024-03-19
• Study First Posted: 2024-03-26
• Last Update Posted: 2024-03-26
• Study Start: 2024-04-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. Histologically confirmed high-grade glioma, with standard radiotherapy and chemotherapy post-surgical resection deemed unsuccessful, and recurrence confirmed by imaging.
2. Age ≥18 and ≤70 years, open to all genders.
3. 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.
4. A Karnofsky Performance Score (KPS) ≥70 or a World Health Organization (WHO) performance status of ≤2.
5. Meets the criteria for acupuncture, with no severe complications, able to undergo acupuncture treatment and demonstrates good compliance.
6. Clear consciousness, with the ability to perceive and distinguish pain, and capable of basic communication.
7. Signed informed consent, voluntarily participating in this study.

Exclusion Criteria

1. Uncontrolled epileptic seizures;
2. Peripheral neuropathy > Grade 1;
3. Currently participating in another clinical trial or having participated in a clinical trial that concluded less than 3 months ago;
4. Previous treatment with paclitaxel or similar chemotherapeutic or biologic agents, or history of allergic reactions to these compounds;
5. 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);
6. Pregnant or breastfeeding women;
7. Individuals with cognitive impairments such as congenital dementia, or with histories of alcohol, drug, or psychotropic substance abuse;
8. Individuals with a history of needle fainting or infections at the site of acupuncture;
9. Patients with conductive foreign bodies within the body;
10. Individuals unable to undergo enhanced MRI examinations.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TMZ group	Temozolomide（TMZ） injection or oral administration	Temozolomide（TMZ） was given orally or intravenously 150mg/(m2·d) for 5 days, repeated every 28 days for 6 cycles
SMES+ABX+TMZ Group	Temozolomide（TMZ） injection or oral administration	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).
SMES+ABX+TMZ Group	Albumin-Bound Paclitaxel(ABX) intravenous drip	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).
SMES+ABX+TMZ Group	Specific mode electroacupuncture stimulation(SMES) intervention	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).

Primary Outcome Measures

Name	Time	Method
Overall survival（OS）	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	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).

Secondary Outcome Measures

Name	Time	Method
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	The period from randomization to the first occurrence of tumor progression or death is meticulously monitored.
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.	The short-term efficacy of the two groups is analyzed, referencing the RANO criteria for assessing the efficacy of solid tumor treatment before and after therapy. Complete Response (CR) is when visible tumor lesions disappear completely, maintained for \>4 weeks (in accordance with RANO criteria and RECIST version 2000). Partial Response (PR) involves a reduction of ≥50% in the sum of the diameters of the tumor lesions, with no increase in other lesions and no new lesions appearing, maintained for \>4 weeks. Stable Disease (SD) is defined as the sum of the diameters of the tumor lesions decreasing by \<50% or increasing by ≤25%, with no new lesions appearing, maintained for \>4 weeks. Progression (PD) occurs when there is an increase of \>25% in the sum
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.	KPS ranges from 0 to 100, with scores directly correlating to quality of life.
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.	ECOG Performance Status is scored from 0 to 5, with scores inversely related to quality of life.
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.	QOL scale for cancer patients assesses quality of life, with a total score ranging from 0 to 60, where scores directly correlate with quality of life.
The Neurological Assessment for Neuro-Oncology (NANO)	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.	NANO Scale quantitatively assesses nine neurological functions in patients, including gait, muscle strength, sensation, visual fields, facial strength, speech, cognition, and limb coordination, with each category scored between 0 to 3 or 0 to 2.

Trial Locations

Locations (1)

The Third Affiliated Hospital of Zhejiang Chinese Medical University; 🇨🇳 Zhejiang, China