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

August 16, 2023 updated by: Marius Zemaitis, Lithuanian University of Health Sciences
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Lithuania
      • Kaunas, Lithuania, LT 44307
        • Recruiting
        • Lithuanian University of Health Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Cryotherapy and Pembrolizumab monotherapy;
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.
Procedure: Bronchoscopic cryotherapy
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.
Drug: Pembrolizumab
As a standard of care, patients will receive pembrolizumab.
Active Comparator: Cryotherapy and Pembrolizumab with platinum-based chemotherapy;
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.
Procedure: Bronchoscopic cryotherapy
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.
Drug: Pembrolizumab
As a standard of care, patients will receive pembrolizumab.
Drug: Platinum based chemotherapy
As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%.
Active Comparator: Pembrolizumab monotherapy;
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).
Drug: Pembrolizumab
As a standard of care, patients will receive pembrolizumab.
Active Comparator: Pembrolizumab with platinum-based chemotherapy;
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).
Drug: Pembrolizumab
As a standard of care, patients will receive pembrolizumab.
Drug: Platinum based chemotherapy
As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy
Time Frame: 6 weeks
Changes in T lymphocyte counts and function in peripheral venous blood assessed via flow cytometry
6 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Necrotic cancer cell death
Time Frame: 6 weeks
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
Time Frame: 1 day
Number of tumor-infiltrating CD4 and CD8 lymphocytes in non-small cell lung cancer biopsy material by immunohistochemistry.
1 day
Objective response rate
Time Frame: 1 year
Assessed according to RECIST and iRECIST criteria
1 year
Progression-free survival
Time Frame: 1 year
The time from the first cycle of systemic treatment to radiologically confirmed disease progression
1 year
Overall survival
Time Frame: 1 year
The time from the first cycle of systemic treatment to death from any cause
1 year
Safety of bronchoscopic cryotherapy and immunotherapy
Time Frame: 1 year
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
Time Frame: 6 weeks
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
Time Frame: 6 weeks
Changes in T lymphocyte effector function in peripheral venous blood evaluated via cytokine panels
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lithuanian University of Health Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Research Council of Lithuania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 21, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LUCACRIMUNO-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings