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.
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.
• Patients diagnosed with advanced non-small cell lung cancer (which includes de novo stage IIIB-IV, according to the 8th edition AJCC, or recurrent disease), documented by histology and/or cytology.
• Presence of brain metastases, candidates for treatment with holocranial radiation therapy.
• Documented EGFR sensitivity mutation.
• Disease measurable by criteria: The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM).
• 18 years and up.
• Functional status, by ECOG scale 0-2
• Life expectancy at least 12 weeks.
• Not receive vasodilator treatment as calcium channel blockers.
• Electrocardiogram
• Neutrophil count 1.5 x 103/mm3, platelet count \>100 x (103/mm3).
• Serum bilirubin should be 1.5 of the upper normal limit (ULN, upper normal limit).
• AST and/or ALT 2 ULN (or 5 x ULN in patients with liver metastases).
• Serum creatinine 1.5 (ULN), or creatinine clearance 60ml/min.
• Ability to comply with study and follow-up procedures.
• Informed written (signed) consent to participate in the study.
• Have tumor tissue (paraffin blocks from diagnostic biopsy) obtained before systemic treatment