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

NCT ID: NCT06000358

Last Updated: 2023-08-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2026-03-31

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.

Conditions

Lung Cancer Stage IV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Bronchoscopic cryotherapy

Intervention Type: 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.

Pembrolizumab

Intervention Type: DRUG

As a standard of care, patients will receive pembrolizumab.

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.

Group Type: ACTIVE_COMPARATOR

Bronchoscopic cryotherapy

Intervention Type: 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.

Pembrolizumab

Intervention Type: DRUG

As a standard of care, patients will receive pembrolizumab.

Platinum based chemotherapy

Intervention Type: DRUG

As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%.

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).

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

As a standard of care, patients will receive pembrolizumab.

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).

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

As a standard of care, patients will receive pembrolizumab.

Platinum based chemotherapy

Intervention Type: DRUG

As a standard of care, patients will receive platinum-based chemotherapy in addition to pembrolizumab if PD-L1 expression is less than 50%.

Interventions

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.

Intervention Type: PROCEDURE

Pembrolizumab

As a standard of care, patients will receive pembrolizumab.

Intervention Type: 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%.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Research Council of Lithuania

OTHER

Sponsor Role: collaborator

Lithuanian University of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Marius Zemaitis

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Lithuanian University of Health Sciences

Kaunas, , Lithuania

Site Status: RECRUITING

Countries

Lithuania

Central Contacts

Marius Zemaitis, PhD, professor

Role: CONTACT

marius.zemaitis@kaunoklinikos.lt

+37061256473

Gediminas Vasiliauskas, PhD student

Role: CONTACT

gediminas.vasiliauskas@kaunoklinikos.lt

+37060403787

Facility Contacts

Rimantas Benetis, PhD, professor

Role: primary

rektoratas@lsmuni.lt

+37037327200

Other Identifiers

LUCACRIMUNO-001

Identifier Type: -

Identifier Source: org_study_id