Clinical Trial Results:
Nitroglycerin's effect on perfusion and hypoxia in human non small cell lung cancer: proof of principle, a phase II trial
Summary
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EudraCT number |
2010-023120-24 |
Trial protocol |
NL |
Global end of trial date |
18 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Apr 2023
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First version publication date |
12 Apr 2023
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Other versions |
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Summary report(s) |
2010-023120-24 Result |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Nitro1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01210378 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Maastro
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Sponsor organisation address |
Dr. Tanslaan 29, Maastricht, Netherlands, 6229 ET
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Public contact |
Chantal Overhof, Maastro, 0031 884455863, chantal.overhof@maastro.nl
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Scientific contact |
Chantal Overhof, Maastro, 0031 884455863, chantal.overhof@maastro.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Nov 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Jun 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Jun 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Demonstrate an absolute increase in 2 year overall survival of 15 % vs historical
controls with a nitroglycerin patch by enhancement of tumor perfusion
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Protection of trial subjects |
- Patient had a minimum of three days to think about participating in the trial;
- Independent physician, who can be consulted with questions;
- Annual safety reporting;
- Monitoring.
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Background therapy |
Patients enrolled in the trial will be requested to undergo repeat scanning with perfusion CT (DCE-CT) scans and hypoxia PET-scans at 2 separate occasions before treatment start; “Baseline” scans: 1 DCE-CT and 1 HX4-PET-scan “Nitroglycerin” scans: 1 DCE-CT and 1 HX-4 PET-scan after administration of nitroglycerin After the first 40 patients completing all scans, the subsequently included 20 patients will only be requested to undergo the baseline scans to evaluate the prognostic value of DCE-CT and hypoxia scanning. The number of 40 patients is chosen to have a sample size which gives a flavour of the normal Gaussian distribution in our patient population. | ||
Evidence for comparator |
If no clear improvement of the OS is observed compared to historical controls, there is no need to embark a more complex randomized phase II and subsequent phase III trial. | ||
Actual start date of recruitment |
01 Dec 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 42
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Worldwide total number of subjects |
42
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EEA total number of subjects |
42
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
28
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From 65 to 84 years |
14
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85 years and over |
0
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Recruitment
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Recruitment details |
In the Netherlands, patients were included in the period from November 2011 until June 2016. From 47 patients enrolled, 42 were eligible. Three patients withdrew their consent and 2 patients were included incorrectly. | ||||||
Pre-assignment
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Screening details |
Inclusion criteria: - Non-small cell lung cancer stage IB-IV amenable for radiotherapy with curative intent. - Patients not included in PET-boost trial - WHO performance status 0-2 - Willing and able to comply with the study prescriptions - 18 years or older | ||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not blinded
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Arms
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Arm title
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Nitroglycerin patch | ||||||
Arm description |
Patient underwent repeated scans, before and after placing a nitroglycerin patch | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
HX4
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Step I: 15ug HX-4
Step II: 27 ug HX-4
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
From 47 patients enrolled, 42 were eligible | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nitroglycerin patch
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Reporting group description |
Patient underwent repeated scans, before and after placing a nitroglycerin patch |
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End point title |
2-year overall survival [1] | ||||||||
End point description |
2-year overall survival
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End point type |
Primary
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End point timeframe |
2-year overall survival
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As discussed with Sjennie Daelmans, as the study was prematurely ended and has only one group. The analysis is not possible/mandatory. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
2 years
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Adverse event reporting additional description |
Physician assessment of CTCAE 4.0, WHO performance status, weight, blood pressure before radiotherapy (RT), weekly during RT, one month after RT, every 3 months thereafter
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
all patients
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Reporting group description |
all patients | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Dec 2011 |
Logistical change (timpoint of the scans) |
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15 Feb 2012 |
Adding the HX-4 administration protocol to the study protocol |
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29 Aug 2012 |
Adaptation of the inclusion criteria and adding a voluntary scan |
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12 Mar 2014 |
Reduction of HX-4, reduction of scanning time, new IB. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/32021913 |