Lung Cancer Stage IVLUCACRIMUNONCT06000358
The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer
A study testing Bronchoscopic cryotherapy, Pembrolizumab and Platinum based chemotherapy in people with Lung Cancer Stage IV, run by Lithuanian University of Health Sciences at 1 site in Lithuania.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Lung Cancer Stage IV
- What is being tested?
- Bronchoscopic cryotherapy, Pembrolizumab and Platinum based chemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteLithuania
- Study dates
- 1 Apr 2023to 31 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
Lithuania1 site, 1 recruiting
- Recruiting
Lithuanian University of Health Sciences
Kaunas, LT 44307
Rimantas Benetis, PhD, professor, +37037327200, rektoratas@lsmuni.lt
About this study
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.
- Conditions
- Lung Cancer Stage IV
- Being tested
- Bronchoscopic cryotherapy, Pembrolizumab, Platinum based chemotherapy
- Keywords
- Pulmonology, Oncology, Immunotherapy, Cryotherapy
- Medical subject headings
- Lung Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchoscopic cryotherapyProcedure or surgery
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.
PembrolizumabDrug
As a standard of care, patients will receive pembrolizumab.
Platinum based chemotherapyDrug
As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Bronchoscopic cryotherapy; Drug: Pembrolizumab |
| 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. Receives: Procedure: Bronchoscopic cryotherapy; Drug: Pembrolizumab; Drug: Platinum based chemotherapy |
| 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). Receives: Drug: Pembrolizumab |
| 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). Receives: Drug: Pembrolizumab; Drug: Platinum based chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 weeks
Secondary outcomes (8)
Necrotic cancer cell death
A change in the concentration of High mobility group box 1 protein (HMGB-1) in venous blood
Measured: 6 weeks
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.
Measured: 1 day
Objective response rate
Assessed according to RECIST and iRECIST criteria
Measured: 1 year
Progression-free survival
The time from the first cycle of systemic treatment to radiologically confirmed disease progression
Measured: 1 year
Overall survival
The time from the first cycle of systemic treatment to death from any cause
Measured: 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.
Measured: 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
Measured: 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
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start1 Apr 2023
- Primary completion31 Mar 2026 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Cancer Stage IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lithuanian University of Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Research Council of Lithuania
- Responsible party
- Principal investigator, Marius Zemaitis, Lithuanian University of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06000358
- Sponsor's protocol ID
- LUCACRIMUNO-001
- Acronym
- LUCACRIMUNO
- Status last verified
- Aug 2023
- First submitted
- 3 Aug 2023
- Last updated
- 21 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06000358
- Acronym / sponsor ID
- LUCACRIMUNO / LUCACRIMUNO-001
- Conditions
- Lung Cancer Stage IV
- Keywords
- Pulmonology, Oncology, Immunotherapy, Cryotherapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Lithuanian University of Health SciencesUniversity, hospital or other
- Collaborators
- Research Council of Lithuania
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 21 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cryotherapy and Pembrolizumab monotherapy; | Active comparator | Procedure: Bronchoscopic cryotherapy, Drug: PembrolizumabPatients 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. |
| Cryotherapy and Pembrolizumab with platinum-based chemotherapy; | Active comparator | Procedure: Bronchoscopic cryotherapy, Drug: Pembrolizumab, Drug: Platinum based chemotherapyPatients 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. |
| Pembrolizumab monotherapy; | Active comparator | Drug: PembrolizumabPatients 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). |
| Pembrolizumab with platinum-based chemotherapy; | Active comparator | Drug: Pembrolizumab, Drug: Platinum based chemotherapyPatients 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). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bronchoscopic cryotherapyThe 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. | Procedure or surgery | Cryotherapy and Pembrolizumab monotherapy;, Cryotherapy and Pembrolizumab with platinum-based chemotherapy; |
| PembrolizumabAs a standard of care, patients will receive pembrolizumab. | Drug | Cryotherapy and Pembrolizumab monotherapy;, Cryotherapy and Pembrolizumab with platinum-based chemotherapy;, Pembrolizumab monotherapy;, Pembrolizumab with platinum-based chemotherapy; |
| Platinum based chemotherapyAs a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%. | Drug | Cryotherapy and Pembrolizumab with platinum-based chemotherapy;, Pembrolizumab with platinum-based chemotherapy; |
Primary outcome
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
8 secondary outcomes
Necrotic cancer cell death
Time frame: 6 weeks
The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment
Time frame: 1 day
Objective response rate
Time frame: 1 year
Progression-free survival
Time frame: 1 year
Overall survival
Time frame: 1 year
Safety of bronchoscopic cryotherapy and immunotherapy
Time frame: 1 year
Changes in T Lymphocyte Function in Response to Cryotherapy and Immunotherapy
Time frame: 6 weeks
Changes in T Lymphocyte Effector Function in Response to Cryotherapy and Immunotherapy
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bronchoscopic cryotherapy, Pembrolizumab and Platinum based chemotherapy in people with Lung Cancer Stage IV, run by Lithuanian University of Health Sciences at 1 site in Lithuania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Lithuania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marius Zemaitis, PhD, professor (+37061256473, marius.zemaitis@kaunoklinikos.lt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in T Lymphocyte Count and Function in Response to Cryotherapy and Immunotherapy (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.