NCT01210378

Brief Summary

Nitroglycerin is a nitric oxide donor which is mainly known as a vasodilating agent used in ischemic heart disease. It has also been shown to increase tumor blood flow in animal and human tumors. The addition of nitroglycerin to chemotherapy in non small cell lung cancer has been shown to generate very favorable response rates with respect to standard treatment schedules\[5\]. Theoretically nitroglycerin might reduce resistance to chemotherapy via a plethora of different effects: better tumor perfusion, direct effects of NO on cancer cells, increase in activated p53 protein and via an increased blood flow in the tumour with as consequence a higher drug concentration in the tumor \[6\] . In mice, nitric oxide donors such as isosorbide dinitrate have been shown to decrease tumor hypoxia by better tumor perfusion, which could enhance radiotherapy responses \[7\]. To date these combined effects have not been tested in humans. In this trial we would like to demonstrate the effect of nitroglycerin on tumor perfusion and hypoxia in non small cell lung cancer (using DCE and HX4 scanning), providing a rationale for further study and to test the effect of combining nitroglycerine to standard treatment of NSCLC (radiotherapy/chemotherapy).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2011

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 27, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 28, 2010

Completed
1.2 years until next milestone

Study Start

First participant enrolled

December 1, 2011

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2017

Completed
Last Updated

February 15, 2019

Status Verified

February 1, 2019

Enrollment Period

4.8 years

First QC Date

September 27, 2010

Last Update Submit

February 12, 2019

Conditions

Non Small Cell Lung Cancer (NSCLC)

Keywords

NSCLCNitroglycerinTumour perfusionHypoxiaToxicityPhase IIHX4

Outcome Measures

Primary Outcomes (1)

  • Increase of 2 year overall survival of 15% vs historical controls

    2 years

Secondary Outcomes (4)

  • Demonstrate effect on enhancement on tumor perfusion

    3 days

  • Toxicity

    7 weeks

  • Demonstrate the effect on enhancement of tumor oxygenation

    3 days

  • Evaluating the possible value of Perfusion CT and hypoxia scans on treatment with nitroglycerin of NSCLC

    2 years

Study Arms (1)

Nitroglycerin

EXPERIMENTAL
Drug: Nitroglycerin patch

Interventions

Nitroglycerin patchDRUG

Nitroglycerin patch

Nitroglycerin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Non-small cell lung cancer stage IB-IV amenable for radiotherapy with curative intent.
  • (Stage IV patients with oligometastic (1-4 metastases) NSCLC are regularly treated radically in the IKNL region).
  • Patients not included in the PET-Boost or the Lucanix trial.
  • WHO performance status 0-2.
  • Willing and able to comply with the study prescriptions.
  • years or older.
  • Ability to give and having given written informed consent before patient registration.
  • No recent (\< 3 months) severe cardiac disease (NYHA class \>1) (congestive heart failure, infarction).
  • No radiotherapy in 4 weeks prior to this study.
  • No treatment with investigational drugs in 4 weeks prior to or during this study.
  • No known allergy to nitroglycerin or nitroglycerin patch.
  • No known allergy to iodine based contrast agents
  • No use of Levitra, Viagra or Cialis at the time of application of the nitroglycerin patch.
  • No conditions necessitating the use of ergot alkaloids, alpha blockers (eg tamsulosine), betablockers or calcium channel blockers on the day of nitroglycerin patch application).
  • No other active malignancy.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

MAASTRO clinic

Maastricht, 6229 ET, Netherlands

Location

Related Publications (1)

  • van Elmpt W, Zegers CML, Reymen B, Even AJG, Dingemans AC, Oellers M, Wildberger JE, Mottaghy FM, Das M, Troost EGC, Lambin P. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion. Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):240-248. doi: 10.1007/s00259-015-3169-4. Epub 2015 Sep 4.

    PMID: 26338178DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungHypoxia

Interventions

Nitroglycerin

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitro CompoundsOrganic Chemicals

Study Officials

  • Philippe Lambin, MD, PhD

    Maastro Clinic, The Netherlands

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 27, 2010

First Posted

September 28, 2010

Study Start

December 1, 2011

Primary Completion

September 1, 2016

Study Completion

March 1, 2017

Last Updated

February 15, 2019

Record last verified: 2019-02

Locations

NL(1)