NCT06238882

Nitroglycerin Plus Radiotherapy Versus Conventional Radiotherapy in Patients With Lung Cancer.

A Phase III Study Comparing Concurrent Nitroglycerin With Radiation Therapy vs Radiation Therapy Alone in Patients With Non-small Cell Lung Cancer With EGFR Mutations and Brain Metastases.

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 74 (estimated)
• Sponsor: Instituto Nacional de Cancerologia de Mexico · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The goal of this interventional phase III clinical trial is to evaluate objective intracranial response rate (iORR) after a treatment with total cranial radiation therapy plus concomitant transdermal nitroglycerin (NTG) addition or total cranial radiation therapy only in patients with stage IV non-small cell lung cancer with brain metastases and EGFR mutation. The main questions it aims to answer are: Determine progression-free survival (PFS) to CNS and overall survival (OS). Evaluate and compare the quality of life (QoL) of patients during and after treatment. Evaluate the cognitive function of patients before, during and after treatment. Evaluate treatment-associated toxicity to grade adverse treatment events Evaluation of HIF1α, VEGF and ROS1 in peripheral blood before and after nitroglycerin treatment. All participants will have laboratory tests at the beginning and end of radiation therapy. Cranial MRI will be performed prior to treatment and 12 weeks after the end of treatment, then every 16 weeks until intracranial progression. Patients in the interventional group will be given 36 mg patches of transdermal nitroglycerin for 24 hours with a 12-hour rest interval during treatment with radiation therapy. The control group will only receive total cranial radiation therapy at the same doses and with the same schedule.

Detailed description

The prognosis of patients with central nervous system (CNS) metastases is poor. About 50% of patients with CPCNP and EGFR mutation have tumor activity in the central nervous system during the first 2 years of diagnosis. Treatment with total cranial radiation therapy (CRT) has shown to have a benefit in local response and patient survival. However, resistance factors such as intratumoral hypoxia decrease the response by CRT. Thus, the use of nitric oxide generators, such as nitroglycerin, has been shown to avoid radio resistance. A previous study conducted at our Institute showed that the addition of transdermal nitroglycerin (NTG) CRT increases intracranial response evaluated by objective radiological response in patients with NSCLC and the subgroup in which a greater benefit was seen was in patients with mutations in the EGFR gene. In this study we propose that the addition of transdermal nitroglycerin to patients with brain metastases and mutations in the EGFR gene receiving CRT will have an increase in intracranial objective response.

Conditions

• Non-small Cell Lung Cancer
• Brain Metastases
• EGFR Gene Mutation

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Nitroglycerin	Patients in the intervention group will receive four 8mg-patches (36 mg final dose) of transdermal nitroglycerin with 10 mg release in 24 hours, for 24 hours with 12-hour rest intervals (to avoid receptor saturation) during treatment with radiation therapy (30 Gy in 10 fractions, or 10 days of treatment).

Timeline

• Start date: 2023-02-23
• Primary completion: 2026-12-23
• Completion: 2027-02-15
• First posted: 2024-02-02
• Last updated: 2026-04-09

Locations

1 site across 1 country: Mexico