Clinical Trial Results:
Phase II study of first-line therapy with Thalidomide in combination with Peg-introna and decrescendo IL-2 in patients with metastatic malignant melanoma
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Summary
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EudraCT number |
2004-005166-20 |
Trial protocol |
DK |
Global end of trial date |
01 Apr 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Oct 2021
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First version publication date |
10 Oct 2021
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Other versions |
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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 |
04.10
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Odense University Hospital
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Sponsor organisation address |
J. B. Winsløws vej 2, entrance 140, basement, Odense C, Denmark, 5000
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Public contact |
Ida Coordt Elle, Odense University Hospital, 45 29335922, ida.coordt.elle@rsyd.dk
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Scientific contact |
Lars Bastholt, Odense University Hospital, 45 24849408, lars.bastholt@rsyd.dk
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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 |
31 Dec 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Apr 2014
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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 |
Determination of efficacy and toxicity of a new combination of drugs
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Protection of trial subjects |
Patients were treated only at three specialized centres in Denmark, with personnel trained in handling the specific known toxicities of this type of treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jan 2007
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Scientific research | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Denmark: 464
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Worldwide total number of subjects |
464
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EEA total number of subjects |
464
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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) |
1
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Adults (18-64 years) |
200
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From 65 to 84 years |
263
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85 years and over |
0
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Recruitment
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Recruitment details |
Between January 2007 and April 2014, 464 Danish patients received high-dose (HD) interleukin-2 (IL-2) and interferon (IFN) as first-line treatment for metastatic melanoma. Our data represent the largest cohort of patients with metastatic melanoma worldwide, with relevant data on all patients and no patients lost to follow-up. | |||||||||
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Pre-assignment
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Screening details |
Baseline staging included patient history; physical examination, ECOG performance status (PS); CT of the brain, neck, chest and abdomen); and blood chemistry, CRP, sodium, potassium, creatinine, ALAT, LDH and alkaline phosphatase. | |||||||||
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Period 1
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Period 1 title |
Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
With the availability of ipilimumab in July 2010 and later also with the approval of drugs targeting BRAF
mutations, relevant second-line treatment option after IL-2 became available. To test the hypothesis of positive impact of these new treatment options, we divided our material into two subgroups, before and after July 1, 2010. We compared the aforementioned biomarkers in
the two groups and subsequent analyses of response rate(RR), PFS and OS were performed.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Before July 1, 2010 | |||||||||
Arm description |
Patients treated before July 1st, 2010 | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Aldesleukin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The HD IL-2 regimen started in week 2 and consisted of
aldesleukin (Proleukin, Novartis): 18 MU/m2 in the first
6 h, 18 MU/m2 in the next 12 h, 18 MU/m2 in the
subsequent 24 h and followed by 4.5 MU/m2 per day for
the next 3 days. IL-2 was administered as continuous
intravenous infusions.
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Investigational medicinal product name |
IFN alpha 2b
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Until July 2009, the IFN
dose was given as IFN alpha 2b (IntronA, ScheringPlough), 10 MU subcutaneous (s.c.), on days 1, 3 and 5.
Thereafter, IFN was given as pegylated IFN alpha 2b,
(PEG-Intron, Schering-Plough), 300 mg s.c., on day 1.
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Arm title
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After July 1st, 2010 | |||||||||
Arm description |
Patients treated after July 1st, 2010. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Aldesleukin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The HD IL-2 regimen started in week 2 and consisted of
aldesleukin (Proleukin, Novartis): 18 MU/m2 in the first
6 h, 18 MU/m2 in the next 12 h, 18 MU/m2 in the
subsequent 24 h and followed by 4.5 MU/m2 per day for
the next 3 days. IL-2 was administered as continuous
intravenous infusions.
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Investigational medicinal product name |
IFN alpha 2b
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Until July 2009, the IFN
dose was given as IFN alpha 2b (IntronA, ScheringPlough), 10 MU subcutaneous (s.c.), on days 1, 3 and 5.
Thereafter, IFN was given as pegylated IFN alpha 2b,
(PEG-Intron, Schering-Plough), 300 mg s.c., on day 1.
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Baseline characteristics reporting groups
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Reporting group title |
Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Before July 1st, 2010
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Baseline demographics and disease characteristics of the treated
population.
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Subject analysis set title |
After July 1st, 2010
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients treated after July 1st, 2010.
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End points reporting groups
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Reporting group title |
Before July 1, 2010
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Reporting group description |
Patients treated before July 1st, 2010 | ||
Reporting group title |
After July 1st, 2010
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Reporting group description |
Patients treated after July 1st, 2010. | ||
Subject analysis set title |
Before July 1st, 2010
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Baseline demographics and disease characteristics of the treated
population.
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Subject analysis set title |
After July 1st, 2010
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Patients treated after July 1st, 2010.
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End point title |
Overall response rate [1] | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
5 years
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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: Please see attached publication for statistical analysis. |
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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 |
No data on toxicity were collected
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Adverse event reporting additional description |
No data on toxicity were collected.
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Assessment type |
Non-systematic | ||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Patients
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Reporting group description |
No data on toxicity were collected. The number of affected subjects is made up. | ||||||||||||||||||||||
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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? No | |||
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/31108244 |
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