Zusanli (ST36) Electroacupuncture Treatment for Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 82
- 试验地点
- 3
- 主要终点
- Neoadjuvant Immunotherapy Conversion Rate
研究概览
简要总结
This study aims to investigate the potential synergistic effects of acupuncture combined with immune checkpoint inhibitors in cancer therapy. Over the past decade, significant progress in cancer immunotherapy has been driven by breakthroughs in understanding immune checkpoint molecules; however, monotherapy with immune checkpoint inhibitors still faces challenges due to low response rates. As a traditional Chinese medical intervention, acupuncture modulates neuro-immune pathways to achieve remote regulation of organ functions, with particular anti-tumor potential observed at the Zusanli (ST36) acupoint-a site located 2 cm below the knee that can be stimulated via electroacupuncture (EA) to improve gastrointestinal function and alleviate inflammation. Preclinical evidence demonstrates that EA suppresses tumor growth in breast cancer models, reduces levels of pro-inflammatory cytokines such as IL-1β and TNF-α, enhances anti-tumor activity of CD8+ T cells and NK cells, and decreases accumulation of immunosuppressive myeloid-derived suppressor cells (MDSCs). Animal studies show that ST36 EA increases key immunomodulatory factors like serum IFN-γ, IL-2, and IL-17, thereby potentiating the efficacy of anti-tumor drugs. Guided by the traditional TCM principle of "reinforcing healthy qi to consolidate the body's resistance," modern clinical applications of EA combined with specific acupoint regimens (e.g., ST36, Sanyinjiao) have effectively alleviated cancer-related pain, chemotherapy-induced side effects, and fatigue. This study will evaluate the safety and immunosensitization effects of ST36 EA combined with PD-1 inhibitors in non-small cell lung cancer patients, employing 1 mA electroacupuncture for 3 consecutive days to activate immune responses. By leveraging acupuncture-induced immune remodeling, this approach aims to provide a novel integrative medicine strategy to overcome resistance to immunotherapy.
详细描述
This study aims to investigate the potential synergistic effects of acupuncture combined with immune checkpoint inhibitors in cancer therapy. Over the past decade, significant progress in cancer immunotherapy has been driven by breakthroughs in understanding immune checkpoint molecules; however, monotherapy with immune checkpoint inhibitors still faces challenges due to low response rates. As a traditional Chinese medical intervention, acupuncture modulates neuro-immune pathways to achieve remote regulation of organ functions, with particular anti-tumor potential observed at the Zusanli (ST36) acupoint-a site located 2 cm below the knee that can be stimulated via electroacupuncture (EA) to improve gastrointestinal function and alleviate inflammation. Preclinical evidence demonstrates that EA suppresses tumor growth in breast cancer models, reduces levels of pro-inflammatory cytokines such as IL-1β and TNF-α, enhances anti-tumor activity of CD8+ T cells and NK cells, and decreases accumulation of immunosuppressive myeloid-derived suppressor cells (MDSCs). Animal studies show that ST36 EA increases key immunomodulatory factors like serum IFN-γ, IL-2, and IL-17, thereby potentiating the efficacy of anti-tumor drugs. Guided by the traditional TCM principle of "reinforcing healthy qi to consolidate the body's resistance," modern clinical applications of EA combined with specific acupoint regimens (e.g., ST36, Sanyinjiao) have effectively alleviated cancer-related pain, chemotherapy-induced side effects, and fatigue. This study will evaluate the safety and immunosensitization effects of ST36 EA combined with PD-1 inhibitors in non-small cell lung cancer patients, employing electroacupuncture during immune therapy and chemotherapy for immune responses. By leveraging acupuncture-induced immune remodeling, this approach aims to provide a novel integrative medicine strategy to overcome resistance to immunotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
The patient did not know in advance whether the use of electroacupuncture or false acupuncture
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤80 years at the time of written informed consent, of either sex;
- •Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) receiving neoadjuvant immunotherapy;
- •Undergoing standard neoadjuvant treatment with chemotherapy plus immunotherapy
- •ECOG performance status score of 0-2;
- •Life expectancy >3 months;
- •At least one measurable target lesion per RECIST 1.1 criteria:
- •Tumor lesions with a long axis ≥10 mm on CT scan (slice thickness ≤5 mm);
- •Lymph node lesions with a short axis ≥10 mm on CT scan;
- •Previously irradiated or locally treated lesions may be designated as target lesions if documented tumor progression post-treatment.
- •Adequate major organ function within 14 days prior to randomization, defined by the following laboratory parameters without blood transfusions, growth factors, albumin, or blood products:
- •Hematological tests: Hemoglobin ≥80 g/L; Absolute neutrophil count >1.5×10⁹/L; Platelet count ≥90×10⁹/L;
- •Biochemical tests: Total bilirubin ≤1.5×ULN (upper limit of normal); ALT/AST ≤2.5×ULN; Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula);
- •Coagulation tests: Prothrombin time (PT) and INR ≤1.5×ULN (unless on warfarin anticoagulation);
- •Cardiac evaluation: Left ventricular ejection fraction (LVEF) ≥50% by Doppler echocardiography.
- •Voluntary participation with signed informed consent, good compliance, and willingness of the patient and their family to cooperate with survival follow-up.
排除标准
- •Pregnant participants;
- •Post-organ transplant patients;
- •Patients with uncontrolled diabetes mellitus, severe cardiac, central nervous system, psychiatric disorders, or coagulopathy;
- •Patients with severe malnutrition;
- •Patients with implanted cardiac pacemakers;
- •Patients with bleeding disorders;
- •Patients with a history of severe allergies or anaphylaxis;
- •Patients with skin infections, lesions, ulcers, or scars at the ST36 (Zusanli) acupoint site;
- •Patients with metal allergy, severe needle phobia, or intolerance to electroacupuncture therapy.
研究组 & 干预措施
Sham electroacupuncture group
干预措施: sham acupuncture (Device)
Electroacupuncture group
干预措施: Acupuncture (Device)
结局指标
主要结局
Neoadjuvant Immunotherapy Conversion Rate
时间窗: Baseline, After neoadjuvant immunotherapy (2-3 cycle, about 2 months after baseline)
Neoadjuvant Immunotherapy Conversion Rate
时间窗: Baseline, After neoadjuvant immunotherapy (2-3 cycle, about 2 months after baseline)
次要结局
- Peripheral blood immune cell alterations(Baseline (Day 1), end of Cycle 1 (21 days), Cycle 2 (42 days), and Cycle 3 (63 days). Each immunotherapy cycle is 21 days)
- Serum and Urine dopamine pathway and metabolites(Baseline (Day 1), end of Cycle 1 (21 days), Cycle 2 (42 days), and Cycle 3 (63 days). Each immunotherapy cycle is 21 days)
研究者
Xuelei Ma MD
Deputy Director (Medical) of the Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University; Associate Director of the Stem Cell Research and Translational Research Laboratory; PhD Supervisor; Professor/Researcher
West China Hospital