About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Parallel
Treatments tested in this trial
Intermittent Hypoxic Training (IHT)
DeviceParticipants 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.
Standard Neoadjuvant Chemo-immunotherapy
Combination productParticipants 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.
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
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.
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.
2-Year Recurrence-Free Survival (RFS) Rate
The percentage of participants who are alive without tumor recurrence or progression at 2 years after 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.
Sponsors and contacts
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zhang yi
Lead sponsor
Xuanwu Hospital, Beijing
Sponsor institution
Capital Medical University
Collaborator
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