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

NCT06000358 | Recruiting

• 1 other identifier: LUCACRIMUNO-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Keywords

Pulmonology; Oncology; Immunotherapy; Cryotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  6 weeks

Secondary Outcomes (8)

• Necrotic cancer cell death

  6 weeks

• The influence of immune cell infiltration in tumor tissue on subsequent cryotherapy and immunotherapy treatment

  1 day

• Objective response rate

  1 year

• Progression-free survival

  1 year

• Overall survival

  1 year

Study Arms (4)

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.

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.

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).

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).

Drug: Pembrolizumab; Drug: Platinum based chemotherapy

Interventions

Bronchoscopic cryotherapy 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.

Cryotherapy and Pembrolizumab monotherapy;; Cryotherapy and Pembrolizumab with platinum-based chemotherapy;

Pembrolizumab DRUG

As a standard of care, patients will receive pembrolizumab.

Cryotherapy and Pembrolizumab monotherapy;; Cryotherapy and Pembrolizumab with platinum-based chemotherapy;; Pembrolizumab monotherapy;; Pembrolizumab with platinum-based chemotherapy;

Platinum based chemotherapy DRUG

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

Cryotherapy and Pembrolizumab with platinum-based chemotherapy;; Pembrolizumab with platinum-based chemotherapy;

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lithuanian University of Health Sciences: lead
• Research Council of Lithuania: collaborator

Study Sites (1)

Lithuanian University of Health Sciences

Kaunas, LT 44307, Lithuania

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Neoplasms

Interventions

pembrolizumab; Platinum Compounds

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Inorganic Chemicals

Central Study Contacts

Marius Zemaitis, PhD, professor

CONTACT

+37061256473; marius.zemaitis@kaunoklinikos.lt

Gediminas Vasiliauskas, PhD student

CONTACT

+37060403787; gediminas.vasiliauskas@kaunoklinikos.lt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 21, 2023
• Study Start: April 1, 2023
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

LI (1)