Clinical trial NCT06000358: The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer
Official title: The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Cancer Stage IV
Keywords: Pulmonology
Oncology
Immunotherapy
Cryotherapy
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
Collaborators: name: Research Council of Lithuania
First posted: 2023-08-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Patients with Eastern Cooperative Oncology Group (ECOG) performance score 0 - 1;
* Patients with histologically confirmed metastatic non-small cell lung cancer and PD-L1 expression on tumor cells was evaluated;
* CT examination shows measurable tumor formations according to the RECIST 1.1 criteria;
* Primary lung tumor or metastasis accessible to flexible bronchoscopy;
* Patients may have received surgery, adjuvant or neoadjuvant chemotherapy prior to the study if it was completed at least 12 months before relapse;
* Patients informed about the purpose and course of the study and provided a written consent to participate.

Exclusion Criteria:

* Patients who refused to participate in the clinical trial and did not sign the informed consent form;
* Men and women under the age of 18, pregnant women;
* Patients belonging to a vulnerable social group;
* High risk of general anesthesia, defined as American Society of Anesthesiologists (ASA) class 4 - 6;
* Documented allergy to medications used during general and local anesthesia, systemic cancer treatment;
* Patients previously treated with immune checkpoint inhibitors;
* EGFR mutations or ALK translocations have been identified in patients;
* Patients with previously diagnosed autoimmune diseases, active viral hepatitis, uncontrolled human immunodeficiency virus (HIV) infection or untreated tuberculosis;
* Patients treated with immunosuppressive drugs, systemic corticosteroids, with equivalent doses of prednisolone exceeding 10 mg/day;
* Patients with an increased risk of bleeding during an interventional procedure;
* Acute untreated conditions that would make it impossible to perform an interventional lung procedure.

Primary outcomes:
measure: Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy
timeFrame: 6 weeks
Secondary outcomes:
measure: Necrotic cancer cell death
timeFrame: 6 weeks
measure: The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment
timeFrame: 1 day
measure: Objective response rate
timeFrame: 1 year
measure: Progression-free survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: Safety of bronchoscopic cryotherapy and immunotherapy
timeFrame: 1 year
measure: Changes in T Lymphocyte Function in Response to Cryotherapy and Immunotherapy
timeFrame: 6 weeks
measure: Changes in T Lymphocyte Effector Function in Response to Cryotherapy and Immunotherapy
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Lithuanian University of Health Sciences
Study officials:
References: