NCT04338867

Nitroglycerin Plus Intracranial Radiotherapy for Brain Metastases in NSCLC Patients

Completed Phase 2 Last updated 22 April 2020

What this trial tests

Phase 2 trial testing Whole-brain radiotherapy in Phase II Clinical Trial in 96 participants. Completed in 1 March 2020.

Timeline

1 March 2020

Primary endpoint
1 March 2020

1 March 2020

Quick facts

Lead sponsor	Instituto Nacional de Cancerologia de Mexico
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	96
Start date	1 March 2020
Primary completion	1 March 2020
Estimated completion	1 March 2020
Sites	1 location across Mexico

Drugs / interventions tested

• Whole-brain radiotherapy

Conditions studied

• Phase II Clinical Trial — all drugs for Phase II Clinical Trial →
• Ninety-six Histologically Confirmed NSCLC Patients With BM — all drugs for Ninety-six Histologically Confirmed NSCLC Patients With BM →
• Randomized 1:1 to Received TN Plus WBR or Only WBR — all drugs for Randomized 1:1 to Received TN Plus WBR or Only WBR →
• ICPFS Evaluated by Two Blinded and Independent Radio-oncologist With MRI — all drugs for ICPFS Evaluated by Two Blinded and Independent Radio-oncologist With MRI →

Sponsor

Instituto Nacional de Cancerologia de Mexico — full company profile →

Who can join

Adults 18 to 90, any sex, with Phase II Clinical Trial or Ninety-six Histologically Confirmed NSCLC Patients With BM. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background: Whole-brain radiotherapy (WBRT) is the standard treatment for multiple brain metastases (BM), in NSCLC patients who are not candidates for treatment with stereotactic radiation body therapy. Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor (VEGFR) induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 alfa in tissues, and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. In this phase II study, we evaluated the effect of transdermal nitroglycerin (TN) on intracranial progression-free survival (ICPFS), objective response rate (ORR) and overall survival (OS) of NSCLC patients with BM.

Material and methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT or WBRT alone. ORR and ICPFS were evaluated by MRI by two independent, blinded radio-oncologists.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics.
   Mintz J, Vedenko A, Rosete O, Shah K, et al · · 2021 · cited 103× · PMID 33513777 · DOI 10.3390/vaccines9020094
2. Nitroglycerin: a comprehensive review in cancer therapy.
   Meunier M, Yammine A, Bettaieb A, Plenchette S. · · 2023 · cited 9× · PMID 37173331 · DOI 10.1038/s41419-023-05838-5
3. Gasotransmitters in Modern Medicine: Promises and Challenges in the Use of Porous Crystalline Carriers.
   Pinto RV, Pinto ML, Serre C. · · 2025 · cited 7× · PMID 40059496 · DOI 10.1002/adhm.202404553
4. In Vitro Drug Repurposing: Focus on Vasodilators.
   Ribeiro E, Costa B, Vasques-Nóvoa F, Vale N. · · 2023 · cited 7× · PMID 36831338 · DOI 10.3390/cells12040671
5. Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial.
   Arrieta O, Hernández-Pedro N, Maldonado F, Ramos-Ramírez M, et al · · 2023 · cited 7× · PMID 35157994 · DOI 10.1016/j.ijrobp.2022.02.010
6. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis.
   Zhang C, Zhou W, Zhang D, Ma S, et al · · 2023 · cited 2× · PMID 36820064 · DOI 10.1515/med-2022-0574
7. Repurposing radiosensitising medicines for radiotherapy: an overview.
   Low JM, Rodriguez-Berriguete G, Higgins GS. · · 2024 · PMID 39886153 · DOI 10.1136/bmjonc-2023-000192