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The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer (LUCACRIMUNO)

Primary Purpose

Lung Cancer Stage IV

Status
Recruiting
Phase
Not Applicable
Locations
Lithuania
Study Type
Interventional
Intervention
Bronchoscopic cryotherapy
Pembrolizumab
Platinum based chemotherapy
Sponsored by
Lithuanian University of Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer Stage IV focused on measuring Pulmonology, Oncology, Immunotherapy, Cryotherapy

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Lithuanian University of Health SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Cryotherapy and Pembrolizumab monotherapy;

Cryotherapy and Pembrolizumab with platinum-based chemotherapy;

Pembrolizumab monotherapy;

Pembrolizumab with platinum-based chemotherapy;

Arm Description

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.

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.

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).

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Necrotic cancer cell death
A change in the concentration of High mobility group box 1 protein (HMGB-1) in venous blood
The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment
Number of tumor-infiltrating CD4 and CD8 lymphocytes in non-small cell lung cancer biopsy material by immunohistochemistry.
Objective response rate
Assessed according to RECIST and iRECIST criteria
Progression-free survival
The time from the first cycle of systemic treatment to radiologically confirmed disease progression
Overall survival
The time from the first cycle of systemic treatment to death from any cause
Safety of bronchoscopic cryotherapy and immunotherapy
Documentation and assessment of adverse treatment events according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Changes in T Lymphocyte Function in Response to Cryotherapy and Immunotherapy
Changes in T lymphocyte function in peripheral venous blood assessed via RNA expression
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

Full Information

First Posted
August 3, 2023
Last Updated
August 16, 2023
Sponsor
Lithuanian University of Health Sciences
Collaborators
Research Council of Lithuania
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1. Study Identification

Unique Protocol Identification Number
NCT06000358
Brief Title
The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer
Acronym
LUCACRIMUNO
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2023 (Actual)
Primary Completion Date
March 31, 2026 (Anticipated)
Study Completion Date
March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lithuanian University of Health Sciences
Collaborators
Research Council of Lithuania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer Stage IV
Keywords
Pulmonology, Oncology, Immunotherapy, Cryotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cryotherapy and Pembrolizumab monotherapy;
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Cryotherapy and Pembrolizumab with platinum-based chemotherapy;
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Pembrolizumab monotherapy;
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Pembrolizumab with platinum-based chemotherapy;
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Procedure
Intervention Name(s)
Bronchoscopic cryotherapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
As a standard of care, patients will receive pembrolizumab.
Intervention Type
Drug
Intervention Name(s)
Platinum based chemotherapy
Intervention Description
As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%.
Primary Outcome Measure Information:
Title
Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy
Description
Changes in T lymphocyte counts and function in peripheral venous blood assessed via flow cytometry
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Necrotic cancer cell death
Description
A change in the concentration of High mobility group box 1 protein (HMGB-1) in venous blood
Time Frame
6 weeks
Title
The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment
Description
Number of tumor-infiltrating CD4 and CD8 lymphocytes in non-small cell lung cancer biopsy material by immunohistochemistry.
Time Frame
1 day
Title
Objective response rate
Description
Assessed according to RECIST and iRECIST criteria
Time Frame
1 year
Title
Progression-free survival
Description
The time from the first cycle of systemic treatment to radiologically confirmed disease progression
Time Frame
1 year
Title
Overall survival
Description
The time from the first cycle of systemic treatment to death from any cause
Time Frame
1 year
Title
Safety of bronchoscopic cryotherapy and immunotherapy
Description
Documentation and assessment of adverse treatment events according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time Frame
1 year
Title
Changes in T Lymphocyte Function in Response to Cryotherapy and Immunotherapy
Description
Changes in T lymphocyte function in peripheral venous blood assessed via RNA expression
Time Frame
6 weeks
Title
Changes in T Lymphocyte Effector Function in Response to Cryotherapy and Immunotherapy
Description
Changes in T lymphocyte effector function in peripheral venous blood evaluated via cytokine panels
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marius Zemaitis, PhD, professor
Phone
+37061256473
Email
marius.zemaitis@kaunoklinikos.lt
First Name & Middle Initial & Last Name or Official Title & Degree
Gediminas Vasiliauskas, PhD student
Phone
+37060403787
Email
gediminas.vasiliauskas@kaunoklinikos.lt
Facility Information:
Facility Name
Lithuanian University of Health Sciences
City
Kaunas
ZIP/Postal Code
LT 44307
Country
Lithuania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rimantas Benetis, PhD, professor
Phone
+37037327200
Email
rektoratas@lsmuni.lt

12. IPD Sharing Statement

Learn more about this trial

The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer

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