Intermittent Hypoxic Training as Neoadjuvant Therapy for Lung Squamous Cell Carcinoma

Official title

Study on the Novel Application of Intermittent Hypoxic Training in Neoadjuvant Therapy for Lung Squamous Cell Carcinoma

Overview

The goal of this clinical trial is to learn if adding intermittent hypoxic training (IHT) to standard neoadjuvant chemo-immunotherapy can increase the pathologic complete response (pCR) rate in patients aged 18 to 75 of both sexes with resectable stage II-IIIA lung squamous cell carcinoma. The main questions it aims to answer are:Can the addition of IHT to standard neoadjuvant chemo-immunotherapy significantly improve the pathologic complete response (pCR) rate compared to standard therapy alone? Is IHT safe and well-tolerated in this perioperative setting, and can it improve 2-year recurrence-free survival (RFS) without increasing complications? Researchers will compare the experimental group (standard neoadjuvant chemo-immunotherapy combined with IHT) to the control group (standard neoadjuvant chemo-immunotherapy alone) to see if the combination safely enhances anti-tumor immune responses, improves tumor regression, and extends long-term survival. Participants will:Receive standard neoadjuvant chemo-immunotherapy for 4 cycles (21 days per cycle), consisting of nab-paclitaxel, carboplatin, and pembrolizumab. Undergo Intermittent Hypoxic Training (IHT) if randomized to the experimental group, using the FLY-2265 low oxygen system (13% $FiO\_2$ for 5 minutes followed by 21% $FiO\_2$ for 5 minutes per cycle; 10 cycles per session, twice daily) for 7 consecutive days starting on Day 1 of each chemo-immunotherapy cycle. Undergo surgery (VATS lobectomy and systematic lymph node dissection) 3 to 4 weeks after the completion of the 4th cycle, provided that the disease has not progressed. Complete regular post-operative follow-up visits (including chest CT scans, brain MRIs, bone scans, tumor markers, and peripheral blood immune monitoring) for up to 5 years to evaluate long-term outcomes.

Interventions

• Device Intermittent Hypoxic Training (IHT)
  Participants will undergo Intermittent Hypoxic Training (IHT) using the FLY-2265 low oxygen system. The training protocol consists of cycles of inhaling 13% FiO2 (fraction of inspired oxygen) for 5 minutes, followed by 21% FiO2 (room air) for 5 minutes. Each session comprises 10 cycles, administered twice daily, for 7 consecutive days. This 7-day training course starts on Day 1 of each 21-day neoadjuvant treatment cycle, for a total of 4 courses.
• Combination product Standard Neoadjuvant Chemo-immunotherapy
  Participants will receive standard clinical doses of neoadjuvant chemo-immunotherapy for 4 cycles (21 days per cycle) prior to surgery. The regimen includes: 1) Nab-paclitaxel; 2) Carboplatin; 3) Pembrolizumab. All agents will be administered via intravenous infusion according to standard clinical oncology guidelines.

Primary outcome measures

• Pathologic Complete Response (pCR) Rate [Time frame: At the time of surgery (approximately 3 to 4 weeks after the completion of the 4th cycle of neoadjuvant therapy).]

Secondary outcome measures (4)

• Major Pathological Response (MPR) Rate [Time frame: At the time of surgery (approximately 3 to 4 weeks after the completion of the 4th cycle of neoadjuvant therapy).]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: From the start of neoadjuvant therapy up to 30 days after surgery (approximately 5 months).]
• 2-Year Recurrence-Free Survival (RFS) Rate [Time frame: 2 years post-surgery.]
• Changes in Peripheral Blood Immune Cell Subsets [Time frame: Baseline (before therapy) and prior to surgery (approximately 12 weeks after baseline).]

Eligibility criteria

Inclusion criteria

• Age between 18 and 75 years old (inclusive), regardless of sex.
• Diagnosed with histologically confirmed stage II-IIIA (according to the AJCC 8th edition staging system) squamous cell lung carcinoma.
• The primary tumor is evaluated by a multidisciplinary team (MDT) and deemed completely resectable.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Life expectancy of at least 6 months.
• Adequate organ, bone marrow, and coagulation functions, meeting the following laboratory criteria within 7 days prior to enrollment:

• Absolute neutrophil count (ANC) >= 1.5 x 10\^9/L;
• Platelet count >= 100 x 10\^9/L;
• Hemoglobin >= 90 g/L;
• Total bilirubin <= 1.5 x upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <= 2.5 x ULN;
• Serum creatinine <= 1.5 x ULN, or creatinine clearance >= 50 mL/min;
• International normalized ratio (INR) and activated partial thromboplastin time (APTT) <= 1.5 x ULN.
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception during the study and for at least 6 months after the last dose. Male participants must agree to use effective contraception during the study and for at least 6 months after the last dose.
• Participant understands the study protocol, voluntarily participates, and signs the written Informed Consent Form (ICF).

Exclusion criteria

• Histologically confirmed small cell lung cancer, adeno-squamous carcinoma, large cell neuroendocrine carcinoma, or adenocarcinoma (including components of these types).
• Patients with driver gene mutations that have approved targeted therapies available (e.g., EGFR mutations, ALK rearrangements, ROS1 fusions, etc.).
• Prior systemic antitumor therapy for lung cancer, including chemotherapy, radiotherapy, immunotherapy, targeted therapy, or definitive surgical resection.
• Active, known, or suspected autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis), or a history of autoimmune disease within the past 2 years.
• History of other malignant tumors within the past 5 years, except for adequately treated cured skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ (e.g., cervical carcinoma in situ).
• Severe cardiovascular or cerebrovascular diseases, including but not limited to:

• Myocardial infarction or unstable angina within the past 6 months;
• New York Heart Association (NYHA) Class III or IV congestive heart failure;
• Clinically significant ventricular arrhythmia or poorly controlled symptomatic arrhythmia;
• Stroke or transient ischemic attack (TIA) within the past 6 months.
• Poorly controlled hypertension (systolic blood pressure >= 160 mmHg and/or diastolic blood pressure >= 100 mmHg despite standard antihypertensive therapy).
• Chronic obstructive pulmonary disease (COPD) or other respiratory diseases with severe lung function impairment (e.g., FEV1 < 50% predicted value, or requiring long-term home oxygen therapy).
• Active infections requiring systemic intravenous anti-infective treatment within 2 weeks prior to enrollment (e.g., severe pneumonia, bacteremia), or active tuberculosis infection.
• Known history of human immunodeficiency virus (HIV) infection, or active Hepatitis B (HBV DNA >= 500 IU/mL or copy number above detection limit) or active Hepatitis C (HCV RNA positive).
• History of interstitial lung disease (ILD), drug-induced pneumonitis, radiation pneumonitis requiring steroid treatment, or evidence of active pneumonitis.
• Severe claustrophobia, severe high-altitude sickness history, or other medical/psychological conditions that prevent compliance with intermittent hypoxic training (IHT) using the FLY-2265 low oxygen system.
• Pregnant or breastfeeding women.
• Any other medical condition, clinical laboratory abnormality, or social circumstance that, in the opinion of the investigator, may compromise participant safety, interfere with the evaluation of study interventions, or affect compliance with study procedures.

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

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Xuanwu Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07618793 · KS2026139 · CFH-2026-2-2014

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗