Non-small Cell Lung CancerNCT06238882
Nitroglycerin Plus Radiotherapy Versus Conventional Radiotherapy in Patients With Lung Cancer.
A study testing Nitroglycerin in people with Non-small Cell Lung Cancer and Brain Metastases, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Non-small Cell Lung Cancer, Brain Metastases, EGFR Gene Mutation
- What is being tested?
- Nitroglycerin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteMexico
- Study dates
- 23 Feb 2023to 15 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- Failure to follow protocol rules.
- Loss of patient follow-up.
- Patients who express their desire not to continue the study.
- Patients with unacceptable toxicity
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Cancerologia
Mexico City, Mexico City, 14080
Oscar G Arrieta, M.D., M.Sc., +525556280400 ext. 44001, ogarrieta@gmail.com
About this study
Official title: 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.
Read more
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.
Read the 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.
- Being tested
- Nitroglycerin
- Keywords
- Radiation therapy, Nitroglycerin, Brain metastases, EGFR mutation, Non-small cell lung cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitroglycerinCombination product
Also called Minitran® Patch
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Intracranial progression-free survival (iPFS) 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.
Measured: 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
Overall survival (OS) 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.
Measured: Duration of patient survival from the date of treatment initiation until until 12 weeks, and every 16 weeks of follow up
QoL
Quality of Life (QoL) measured by EORTC QLQ C30/LC13 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.
The EORTC QLQ-C30 questionnaire consists of 30 questions with five functional scores (physical, role, cognitive, emotional and social); a global health status score three symptom scale score (fatigue, pain, nausea and vomiting); and six independent one-it.
All scale and single-item scores can be linearly transformed to a score ranged from 0 to 100. A higher score of global health and functional subscriptions indicates better functioning.
Measured: 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
Evaluate the cognitive function of patients with lung cancer and brain metastases treated with nitroglycerin vs radiation therapy alone before, during and after treatment using the Neuropsi Attention and Memory (NAM) instrument.
NEUROPSI evaluates attention, memory, and learning functioning in Spanish speakers.
Subtests are organized into summary scores that yield a General Attention and Memory Index Score, an Attention Index, Memory Index, and each of the subtests.
Subtests evaluate Orientation, Attention and Concentration, Working Memory, Immediate Verbal Memory, Delayed Verbal Memory, Immediate Visual Memory, Delayed Verbal Memory, and Executive Functions.
The Neuropsi Attention and Memory includes theoretical updates and new test scores indexes. It includes an adjustment of the norms of Total Attention and Executive Functions and Total Attention and Memory according to the modification of the tasks of digit detection and Stroop test.
Measured: 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
Treatment-related toxicity 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 using NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 to grading adverse events (AE).
A grading (severity) scale is provided for each AE term. The CTCAE displays Grades 1 through 5:
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL*.
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**.
Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: Thee date of day 1, 7 and 10 of therapy and the date of 12 weeks after treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2024
- Study start23 Feb 2023
- Primary completion23 Dec 2026 (estimated)
- Study completion15 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cancerologia de Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Oscar Gerardo Arrieta Rodríguez, Instituto Nacional de Cancerologia de Mexico
- Investigators
- Oscar G Arrieta, M.D., M.Sc., Principal investigator, Instituto Nacional de Cancerologia de Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06238882
- Sponsor's protocol ID
- (023/013/ICI)(CEI/083/22)
- Status last verified
- Apr 2026
- First submitted
- 22 Jan 2024
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT06238882
- Acronym / sponsor ID
- (023/013/ICI)(CEI/083/22)
- Keywords
- Radiation therapy, Nitroglycerin, Brain metastases, EGFR mutation, Non-small cell lung cancer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Instituto Nacional de Cancerologia de MexicoUniversity, hospital or other
- Study start
- 23 Feb 2023 (actual)
- Primary completion
- 23 Dec 2026 (estimated)
- Study completion
- 15 Feb 2027 (estimated)
- First posted
- 2 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Combination Product: NitroglycerinPatients will be given patches of nitroglycerin during treatment with radiation therapy (30 Gy in 10 fractions, i.e. 10 days of treatment). |
| Control | No intervention | –Patients will be given a conventional treatment with radiation therapy (30 Gy in 10 fractions, i.e. 10 days of treatment). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NitroglycerinAlso: Minitran® PatchPatients 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). | Combination product | Intervention |
Primary outcome
iORR
Time frame: 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.
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.
5 secondary outcomes
iPFS
Time frame: 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
Time frame: Duration of patient survival from the date of treatment initiation until until 12 weeks, and every 16 weeks of follow up
QoL
Time frame: 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
Time frame: 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
Time frame: Thee date of day 1, 7 and 10 of therapy and the date of 12 weeks after treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oscar G Arrieta, M.D., M.Sc. principal investigator
Instituto Nacional de Cancerologia de Mexico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitroglycerin in people with Non-small Cell Lung Cancer and Brain Metastases, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oscar G Arrieta, M.D., M.Sc. (+525556280400 ext. 44001, ogarrieta@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
iORR (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.