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

NCT06238882 | Recruiting

• 1 other identifier: (023/013/ICI)(CEI/083/22)
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Radiation therapy; Nitroglycerin; Brain metastases; EGFR mutation; Non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• iORR

  Objective intracranial response rate (iORR) in patients with lung cancer and brain metastases treated with total cranial radiation therapy plus concomitant transdermal nitroglycerin addition versus patients treated with total cranial radiation therapy only.

  From date after radiation treatment until the first documented progression date, or last evaluable assessment in the absence of progression, or death from any cause, whichever comes first, to 12 weeks of follow up.

Secondary Outcomes (5)

• iPFS

  From date of treatment initiation until date of disease progression or worsening until 12 weeks, and every 16 weeks of follow up until progression.

• OS

  Duration of patient survival from the date of treatment initiation until until 12 weeks, and every 16 weeks of follow up

• QoL

  A day before, within, and a day after the date of treatment initiation until date of disease progression or worsening or 12 weeks, and every 16 weeks of follow up.

• Cognitive function

  A day before, within, and a day after the date of treatment initiation until date of disease progression or worsening or 12 weeks, and every 16 weeks of follow up.

• Treatment-related Toxicity

  Thee date of day 1, 7 and 10 of therapy and the date of 12 weeks after treatment.

Study Arms (2)

Intervention

EXPERIMENTAL

Patients will be given patches of nitroglycerin during treatment with radiation therapy (30 Gy in 10 fractions, i.e. 10 days of treatment).

Combination Product: Nitroglycerin

Control

NO INTERVENTION

Patients will be given a conventional treatment with radiation therapy (30 Gy in 10 fractions, i.e. 10 days of treatment).

Interventions

Nitroglycerin COMBINATION_PRODUCT

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).

Also known as: Minitran® Patch

Intervention

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, ischemic heart disease, liver, kidney disease).
• Patients with a history of allergy to glyceryl tinistate
• Any other malignant pathology within the previous 5 years (except for cervical carcinoma in situ or basal-cell skin cancer, treated appropriately).
• Pregnant and/or breastfeeding women.
• Meningeal carcinomatosis corroborated by cytopathological study.
• Disposal Criteria:
• Failure to follow protocol rules.
• Loss of patient follow-up.
• Patients who express their desire not to continue the study.
• Patients with unacceptable toxicity

Sponsors & Collaborators

• Instituto Nacional de Cancerologia de Mexico: lead

Study Sites (1)

Instituto Nacional de Cancerologia

Mexico City, Mexico City, 14080, Mexico

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Nitroglycerin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals

Study Officials

• Oscar G Arrieta, M.D., M.Sc.

  Instituto Nacional de Cancerologia de Mexico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oscar G Arrieta, M.D., M.Sc.

CONTACT

+525556280400; ogarrieta@gmail.com

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: Head of Thoracic Oncology Unit

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 2, 2024
• Study Start: February 23, 2023
• Primary Completion (Estimated): December 23, 2026
• Study Completion (Estimated): February 15, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

ME (1)