Pulse Radiotherapy to Overcome Metastatic Immune System Evasion in Lung Cancer

Trial Title: Pulse Radiotherapy to Overcome Metastatic Immune System Evasion in Lung Cancer

NCT ID: NCT06622174

Condition: Non Small Cell Lung Cancer
Metastatic Lung Cancer

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung

Conditions: Keywords:
Non small cell lung cancer
Metastatic lung cancer
Progressive disease
Polymetastatic
Immunotherapy resistance
Radiotherapy
Pulse radiotherapy

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Pulse radiotherapy
Description: Pulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle
Arm group label: Pulse Radiotherapy

Summary: This phase I study aims to evaluate the safety and effectiveness of adaptive pulsed radiotherapy combined with immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) resistant to immune checkpoint inhibitors. The primary goal is to assess treatment-related toxicity, while secondary objectives include progression-free survival, overall survival, and quality of life. The study will enroll 32 patients.

Detailed description: Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is a leading cause of cancer-related death globally. Despite the success of immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1, many patients develop resistance to these therapies, either at the start (primary resistance) or over time (secondary resistance). This resistance leads to disease progression during or after treatment, posing a major clinical challenge. Recent studies suggest that combining ICIs with radiotherapy may improve treatment outcomes. Advances in pulsed radiotherapy, including stereotactic radiation cycles, have shown promising results in overcoming ICI resistance in metastatic disease. Objective: This phase I prospective study aims to evaluate the safety (primary objective) and efficacy of pulsed radiotherapy in combination with PD(L)-1 inhibitors (with or without chemotherapy) in patients with polymetastatic NSCLC who have developed systemic resistance. The hypothesis is that this combination approach could improve patient outcomes by directly reducing tumor burden and enhancing the immune response, while maintaining an acceptable toxicity profile. Methods: This single-arm phase I study will enroll 32 patients with NSCLC who show disease progression in ≥ 5 extracranial sites while on PD(L)-1 inhibitors (with or without chemotherapy). Pulsed radiotherapy will be delivered in up to 3 cycles, targeting 2 to 5 progressive lesions per cycle. Eligible participants must be 18 years or older, with systemic progression of NSCLC in ≥ 5 sites during treatment with ICIs, and an ECOG performance status of 0-2. Brain metastases are permitted but will not be included in the lesion count. The primary endpoint is dose-limiting toxicity (DLT), defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, focusing on grade 3-5 adverse events related to radiotherapy within 180 days of treatment. Secondary endpoints include the development of a clinical workflow for adaptive pulsed radiotherapy, progression-free survival (PFS), overall survival (OS), local recurrence, time to the next systemic treatment, and patient-reported quality of life.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Participants must be ≥ 18 years old - Ability to provide written informed consent - Actively receiving PD(L)-1 inhibitors - Progressive disease defined as per RECIST criteria 1.1 on CT metrics as a greater than 20% increase in the sum measurement of lesions, non-target unequivocal progressive disease or a new lesion on CT. - Radiological progression to ≥ 5 disease sites. Progression at the primary tumor site should be counted within the total number of progressive lesions. For patients with lymph node metastases, each node is counted as one site of metastasis. - Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. - Patients with brain metastasis are allowed and should be treated as per standard of care - All sites of disease can, in the opinion of the investigator, be safely treated and targetable with high-to-intermediate or low dose radiotherapy (taking into account prior local therapy, organ function and underlying medical condition such as inflammatory bowel disease, pulmonary fibrosis, etc.) - Patients with prior metastases that have been treated with ablative therapies (e.g. radiotherapy, surgery or radiofrequency ablation) before their current line of systemic therapy, are eligible. - Patients receiving additional systemic therapy agents such as chemotherapy are eligible, provided the other systemic agents are temporarily halted during radiation treatment. Exclusion Criteria: - Pregnant or breastfeeding individuals are excluded. - Medical conditions that would hinder the safe administration of radiotherapy or follow-up. - Patients who are ineligible for immunotherapy. - Patients with a history of pneumonitis are excluded. - Presence of an active autoimmune disease.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Centre Hospitalier de l'Université de Montréal

Address:
City: Montréal
Country: Canada

Contact:
Last name: Mom Phat

Phone: 514-890-8254
Email: mom.phat.chum@ssss.gouv.qc.ca

Investigator:
Last name: Houda Bahig, MD PhD
Email: Principal Investigator

Start date: April 2025

Completion date: August 2027

Lead sponsor:
Agency: Houda Bahig
Agency class: Other

Collaborator:
Agency: Varian, a Siemens Healthineers Company
Agency class: Industry

Source: Centre hospitalier de l'Université de Montréal (CHUM)

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06622174