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| Name | Class |
|---|---|
| Research Council of Lithuania | OTHER |
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Lung cancer remains one of the most commonly diagnosed oncological diseases worldwide and the first in terms of mortality. Although immune checkpoint inhibitors form the backbone of current metastatic non-small cell lung cancer treatments, there is still no ideal predictive marker for its efficacy and patients still achieve suboptimal results in overall response and survival. While immune checkpoint inhibitors are known to shift systemic anti-tumor immune response from suppression to stimulation in some patients, the investigators hypothesize that this effect can be further enhanced by cryotherapy, especially in "cold" tumors. If proven successful, cryotherapy in combination with immunotherapy, could potentiate a more powerful immune response compared to systemic therapy alone, improve overall response rate, patients' survival without disease progression, and overall survival. The investigators, therefore, aim to use combined local tumor cryotherapy, combined with immune checkpoint inhibitor therapy to induce and evaluate systemic anti-tumor T lymphocyte response and achieve improved non-small cell lung cancer patient outcomes than with immunotherapy alone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cryotherapy and Pembrolizumab monotherapy; | Active Comparator | Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment. |
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| Cryotherapy and Pembrolizumab with platinum-based chemotherapy; | Active Comparator | Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment. |
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| Pembrolizumab monotherapy; | Active Comparator | Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations). |
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| Pembrolizumab with platinum-based chemotherapy; | Active Comparator | Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bronchoscopic cryotherapy | Procedure | The cryotherapy procedure is performed before the start of systemic treatment, under visual (for endobronchial cryotherapy) or radial EBUS and fluoroscopy control (for transbronchial cryotherapy), ensuring the correct position of the cryoprobe in the tumor. After being placed in the correct position. After being placed in the correct position, the cryoprobe is cooled using CO2 and allowed to cool passively. The cooling-thawing stages are repeated for a total of 3 cycles. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy | Changes in T lymphocyte counts and function in peripheral venous blood assessed via flow cytometry | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Necrotic cancer cell death | A change in the concentration of High mobility group box 1 protein (HMGB-1) in venous blood | 6 weeks |
| The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marius Zemaitis, PhD, professor | Contact | +37061256473 | marius.zemaitis@kaunoklinikos.lt | |
| Gediminas Vasiliauskas, PhD student | Contact | +37060403787 | gediminas.vasiliauskas@kaunoklinikos.lt |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lithuanian University of Health Sciences | Recruiting | Kaunas | LT 44307 | Lithuania |
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| Pembrolizumab | Drug | As a standard of care, patients will receive pembrolizumab. |
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| Platinum based chemotherapy | Drug | As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%. |
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Number of tumor-infiltrating CD4 and CD8 lymphocytes in non-small cell lung cancer biopsy material by immunohistochemistry.
| 1 day |
| Objective response rate | Assessed according to RECIST and iRECIST criteria | 1 year |
| Progression-free survival | The time from the first cycle of systemic treatment to radiologically confirmed disease progression | 1 year |
| Overall survival | The time from the first cycle of systemic treatment to death from any cause | 1 year |
| Safety of bronchoscopic cryotherapy and immunotherapy | Documentation and assessment of adverse treatment events according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. | 1 year |
| Changes in T Lymphocyte Function in Response to Cryotherapy and Immunotherapy | Changes in T lymphocyte function in peripheral venous blood assessed via RNA expression | 6 weeks |
| Changes in T Lymphocyte Effector Function in Response to Cryotherapy and Immunotherapy | Changes in T lymphocyte effector function in peripheral venous blood evaluated via cytokine panels | 6 weeks |
| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D017671 | Platinum Compounds |
| ID | Term |
|---|---|
| D007287 | Inorganic Chemicals |
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