Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Argon-helium cryoablation, PD-1 inhibitor, Non-small cell lung cancer, Randomized controlled trial, Efficacy, Immune function
Brief summary
This randomized controlled trial investigated the efficacy and safety of argon-helium cryoablation combined with PD-1 inhibitors compared to PD-1 inhibitors plus chemotherapy for treating non-small cell lung cancer (NSCLC). The study aimed to evaluate differences in survival, tumor response, immune function, and adverse events.
Detailed description
This was a single-center, open-label, randomized controlled trial conducted at the First Hospital of Hebei Medical University, China. Sixty patients with advanced non-small cell lung cancer (NSCLC) were enrolled between December 2020 and December 2023. Patients were randomly assigned (1:1) to either a study group (argon-helium cryoablation combined with PD-1 inhibitor, Camrelizumab) or a control group (PD-1 inhibitor, Camrelizumab, combined with platinum-based doublet chemotherapy). Argon-helium cryoablation was performed prior to PD-1 inhibitor administration in the study group. Both groups received 4 cycles of systemic therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), changes in immune function markers (CD4+, CD8+, CD4+/CD8+ ratio), and adverse reactions. Patients were followed for up to 1 year. The study aimed to determine if combining cryoablation with PD-1 inhibition offers superior outcomes compared to standard chemo-immunotherapy in NSCLC.
Interventions
DEVICEArgon-Helium Cryoablation
Procedure performed within 7 days before the first dose of PD-1 inhibitor. CT-guided insertion of cryoprobes into the target tumor. Two freeze-thaw cycles: rapid freeze to -135°C to -145°C for 15-20 minutes, followed by thawing.
DRUGCamrelizumab
200 mg intravenously every 3 weeks for 4 cycles.
* Non-squamous NSCLC: Pemetrexed (500 mg/m² IV on day 1) plus Carboplatin (AUC 5 mg/mL•min IV on day 1) of each 3-week cycle. * Squamous NSCLC: Gemcitabine (1250 mg/m² IV on days 1 and 8) plus Carboplatin (AUC 5 mg/mL•min IV on day 1) of each 3-week cycle. * Administered for 4 cycles.
Sponsors
The First Hospital of Hebei Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed NSCLC, stage IIIB, IIIC, or IV (AJCC 8th Edition); * At least one measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); * Estimated survival time ≥6 months; * Receiving argon-helium cryoablation combined with PD-1 inhibitor for the first time at our institution (for study group) or standard chemo-immunotherapy (for control group); * Unable or unwilling to undergo surgical resection for various reasons; * Karnofsky Performance Status (KPS) score ≥60; * Conscious and capable of effective communication; * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
Exclusion criteria
* Presence of other active malignant tumors; * Significant uncontrolled hepatic (total bilirubin \>1.5 × upper limit of normal \[ULN\], AST/ALT \>2.5 × ULN or \>5 × ULN if liver metastases present) or renal dysfunction (creatinine clearance \<50 mL/min); * Non-primary NSCLC (i.e., metastatic from another site); * Known allergy or contraindication to study drugs or inability to comply with the treatment plan; * Coexisting active tuberculosis, uncontrolled systemic infections, or other significant pulmonary diseases that would interfere with treatment or outcome assessment; * Pregnancy or lactation; * Severe psychiatric disorders; * Uncorrected coagulation disorders (e.g., INR \>1.5 or platelet count \<75 × 109/L); * Known immunodeficiency syndromes (e.g., HIV infection); * Symptomatic hemorrhagic pleural effusion requiring urgent intervention; * Patients who withdrew consent before randomization or were deemed non-compliant by investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization until death, assessed through study completion, an average of 1 year. | Time from randomization to death from any cause. |
| Progression-Free Survival (PFS) | From randomization until disease progression or death, assessed through study completion, an average of 1 year. | Time from randomization to disease progression (RECIST 1.1) or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD4+ T lymphocyte counts | Baseline (Day 1, prior to treatment) and at the end of Cycle 4 (each cycle is 21 days). | Change in peripheral blood CD4+ T lymphocyte subset counts from baseline. |
| Change in CD8+ T lymphocyte counts | Baseline (Day 1, prior to treatment) and at the end of Cycle 4 (each cycle is 21 days). | Change in peripheral blood CD8+ T lymphocyte subset counts from baseline. |
| Objective Response Rate (ORR) | Assessed after 4 cycles of treatment (each cycle is 21 days), at approximately 12 weeks from randomization. | Proportion of patients achieving Complete Response (CR) or Partial Response (PR) according to mRECIST criteria. |
| Incidence and severity of Adverse Events (AEs) | From the first dose of study treatment until 30 days after the last dose of study medication (up to approximately 16 weeks). | Number and grade of AEs according to NCI-CTCAE v5.0. |
| 1-year Progression-Free Survival Rate | At 1 year from randomization. | Proportion of patients alive and without disease progression at 1 year from randomization. |
| Change in CD4+/CD8+ T lymphocyte ratio | Baseline (Day 1, prior to treatment) and at the end of Cycle 4 (each cycle is 21 days). | Change in the ratio of peripheral blood CD4+ to CD8+ T lymphocytes from baseline. |
| Disease Control Rate (DCR) | Assessed after 4 cycles of treatment (each cycle is 21 days), at approximately 12 weeks from randomization. | Proportion of patients achieving CR, PR, or Stable Disease (SD) according to mRECIST criteria. |
Countries
China
Outcome results
None listed