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.

Plain English Summary

Nitroglycerin Plus Radiotherapy Versus Conventional Radiotherapy in Patients With Lung Cancer. is a Not Applicable clinical trial sponsored by Instituto Nacional de Cancerologia de Mexico studying Non-small Cell Lung Cancer, Brain Metastases, EGFR Gene Mutation. This trial tests if adding nitroglycerin to radiation therapy improves outcomes for lung cancer patients with brain metastases. It is for patients diagnosed with advanced non-small cell lung cancer that has spread to the brain and has a specific genetic mutation (EGFR). Participants will receive radiation therapy, and some will also receive nitroglycerin patches. The alternative is standard radiation therapy alone. The trial aims to enroll 74 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have advanced non-small cell lung cancer with brain metastases and an EGFR mutation, and are well enough to participate. You cannot join if you have other unstable serious health conditions, are pregnant or breastfeeding, or have had other cancers recently (with some exceptions). Specific blood test results and heart function are also required. This trial is studying Non-small Cell Lung Cancer, Brain Metastases, EGFR Gene Mutation, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if the combination treatment shrinks tumors in the brain more effectively than radiation alone. The specific primary outcome measures are: iORR (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.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial addresses a critical need for better treatments for lung cancer that has spread to the brain, a common and difficult complication. This research targets Non-small Cell Lung Cancer, Brain Metastases, EGFR Gene Mutation, where improved treatment options are needed.

Investor Insight

This trial explores a novel combination therapy for a challenging cancer complication, potentially opening new treatment avenues if successful.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of both radiation therapy and nitroglycerin. Understand what the daily schedule will be for radiation and nitroglycerin patch application. Be prepared for regular MRI scans and blood tests throughout the study. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 74 participants

Interventions

• 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).

Primary Outcomes

• iORR (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

• 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.)

Full Eligibility Criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Trial Locations

• Instituto Nacional de Cancerologia, Mexico City, Mexico City, Mexico

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Brain Metastases
• EGFR Gene Mutation
• Lung Cancer
• Cancer Metastasis
• Oncology
• Radiation Therapy
• Targeted Therapy
• Neurology
• Thoracic Oncology

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