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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
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.
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.
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Pathologic Complete Response (pCR) Rate
The percentage of participants who achieve pathologic complete response, defined as the complete disappearance of all invasive tumor cells in the completely resectable lung cancer specimen and all sampled regional lymph nodes (ypT0N0) following neoadjuvant therapy.
Time frame: At the time of surgery (approximately 3 to 4 weeks after the completion of the 4th cycle of neoadjuvant therapy).
Major Pathological Response (MPR) Rate
The percentage of participants with 10% or less viable tumor cells remaining in the resected primary tumor specimen following neoadjuvant therapy.
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)
Safety and tolerability evaluated by grading and recording adverse events, compliance with intermittent hypoxic training, and delay or discontinuation of neoadjuvant therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: From the start of neoadjuvant therapy up to 30 days after surgery (approximately 5 months).
2-Year Recurrence-Free Survival (RFS) Rate
The percentage of participants who are alive without tumor recurrence or progression at 2 years after surgery.
Time frame: 2 years post-surgery.
Changes in Peripheral Blood Immune Cell Subsets
Evaluation of tumor immune microenvironment factors and systemic immunity, including the percentage of CD8+ T cells, CD4+ T cells, and the CD4+/CD8+ T-cell ratio measured by flow cytometry.
Time frame: Baseline (before therapy) and prior to surgery (approximately 12 weeks after baseline).
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