Acupuncture for Enhancing Immunotherapy in Advanced NSCLC：a Pilot Study

Acupuncture for Enhancing the Effect of Immunotherapy in Advanced NSCLC: a Pilot Study

This multicentre, randomized controlled trial evaluates the effect and safety of integrating acupuncture with immunotherapeutic sensitization in treating NSCLC. Participants will be randomly assigned to undergo either acupuncture or sham acupuncture concurrent with the initial four cycles of standard ICIs combined with chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer; Non-Small-Cell Lung Carcinoma
• Intervention / Treatment: Procedure: acupuncture; Procedure: Sham acupuncture

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Guangdong Provincial Hospital of Chinese Medicine
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Guangzhou University of Chinese Medicine.
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Provincial Hospital of Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has a histologically-confirmed or cytologically confirmed diagnosis of stage IIIB or IV NSCLC.
2. PD-L1 TPS<50%
3. EGFR/ALK wild-type
4. Has not received prior systemic treatment for advanced NSCLC. For patients who received preoperative neoadjuvant chemotherapy or postoperative adjuvant chemotherapy or radical chemoradiotherapy, if the disease progresses occurred one six months after the last treatment, they can be enrolled. Patients who received targeted therapy or immunotherapy can not be enrolled.
5. Has a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
6. Age≥18 years
7. Has a life expectancy of at least 3 months
8. Has measurable disease
9. Has adequate organ function
10. Voluntarily enrolled into the study, sign the informed consent form and have good compliance

Exclusion Criteria:

1. Unable to complete baseline assessments
2. Expected to receive radiotherapy within the next 4 cycles
3. With a combination of serious primary diseases of the heart, cerebrovascular, hepatic, renal, and hematopoietic systems
4. With dementia, neurological disorders, mental retardation, or language impairment, and pregnant or breastfeeding women
5. Combined autoimmune diseases, hematologic disorders, or long-term use of hormones or immunosuppressive drugs
6. Combined with a primary tumor from other sites
7. Had participated in any other clinical trial within the prior 3 months
8. Has known history of Human Immunodeficiency Virus (HIV) or solid organ transplantation
9. With legal incapacity
10. With skin breakdown at the acupuncture point that interferes with treatment
11. With a pacemaker
12. With a fear of acupuncture
13. Had received acupuncture treatment within 6 weeks
14. Has known active Hepatitis B
15. Has interstitial lung disease or a history of pneumonitis that required oral of IV glucocorticoids to assist with management
16. Has fever (>38°C) or clinically significant infection within 1 week prior to enrolment
17. Has active tuberculosis or indications of severe or uncontrolled systemic diseases
18. With a bleeding tendency, and receiving thrombolytics or anticoagulants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acupuncture; Acupuncture for 4 times every 3 weeks (one cycle of ICIs combined with chemotherapy) for 12 weeks (4 cycles of ICIs combined with chemotherapy)	Procedure: acupuncture; Acupuncture at Neiguan(PC6), Zhongwan (CV12), Guanyuan (CV 4), Baihui (DU20), Yintang (GV29), combined with electro-acupuncture at Zusanli(ST36), and Sanyinjiao (SP-6).
Sham Comparator: Sham acupuncture; Sham acupuncture for 4 times every 3 weeks (one cycle of ICIs combined with chemotherapy) for 12 weeks (4 cycles of ICIs combined with chemotherapy)	Procedure: Sham acupuncture; Sham acupuncture at Neiguan(PC6), Zhongwan (CV12), Guanyuan (CV 4), Baihui (DU20), Yintang (GV29), combined with sham electro-acupuncture at Zusanli(ST36), and Sanyinjiao (SP-6).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progress free survival defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is defined as the time until death due to any cause	From date of randomization until the date of death from any cause, assessed up to 5 years.
Objective response rate	Objective response rate is defined as the proportion of patients achieving complete (iCR/CR) or partial (iPR/PR) response according to iRECIST or RECIST V.1.1 criteria	Through study completion, an average of 3 years.
Disease control rate	Disease control rate is determined by the percentage of patients who achieve CR, PR, or SD as defined by iRECIST or RECIST V.1.1 criteria. This encompasses all instances of CR, PR, and SD (CR + PR + SD).	Through study completion, an average of 3 years.
Duration of response	Duration of response is assessed only in patients achieving CR, PR, or nPR and was defined as the time from first assessment showing CR, PR, or nPR to earliest date of either PD or death.	Through study completion, an average of 3 years.
Quality of life evaluation	According to the requirements of European Organisation for Research and Treatment of Cancer-quality of life core questionnaire (EORTC QLQ-C30)/Lung cancer 13 items (LC13), the scoring results of each field of the scale were recorded in CRF. The score of this questionnaire ranges between 1 and 4. The higher score indicates the worse quality of life.	At the baseline, day 8 of Cycle 1-4 (each cycle is 21 days), and day 1 of Cycle 5 (each cycle is 21 days), up to approximately 6 months.
Symptom evaluation	According to the requirements of Lung cancer symptom scale (LCSS), the scoring results of each field of the scale were recorded in CRF. The score of this questionnaire ranges between 0 and 10. The higher score indicates the worse symptom.	At the baseline, day 8 of Cycle 1-4 (each cycle is 21 days), and day 1 of Cycle 5 (each cycle is 21 days), up to approximately 6 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Next-generation sequencing	Biopsy/surgery samples were examined histopathologically and for reptarenavirus RNA by qRT-PCR and metagenomic NGS. Genetic testing of tissue samples was performed by NGS.	At the baseline and the date of first documented progression, up to approximately 36 months.
Cytometry by time-of-flight	Cells were analyzed using a CyTOF mass cytometer	At the baseline and the date of first documented progression, up to approximately 36 months.
Tumor markers	Detection of tumor markers including serum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma (SCC), carbohydrate antigen 125 (CA125) and cytokeratin 19 fragment (CyFRA21-1).	At the baseline and the date of first documented progression, up to approximately 36 months.
Pro-inflammatory index	Pro-inflammatory index were measured from the peripheral blood.	At the baseline and the date of first documented progression, up to approximately 36 months.
The traditional Chinese medicine syndrome evaluation	The data related to Chinese medicine syndrome types will be extracted, including symptoms and signs, tongue, pulse, and other syndrome information.	At the baseline, the end of Cycle 2 (each cycle is 21 days), and day 1 of Cycle 5 (each cycle is 21 days), up to approximately 6 months.

Collaborators and Investigators

• Sponsor: Guangzhou University of Traditional Chinese Medicine
• Collaborators: Jiangsu Province Hospital of Traditional Chinese Medicine; The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
• Investigators: Principal Investigator: Haibo Zhang, M.D., Guangdong Provincial Hospital of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Non-Small Cell Lung Cancer; Acupuncture; Immune Checkpoint Inhibitors; Effect
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Complementary Therapies; Acupuncture Therapy
• Other Study ID Numbers: 2023YFC3503303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No