Clinical Trial Results:
Phase II Studie zur Wirksamkeit und Verträglichkeit von Vorinostat bei Patienten mit fortgeschrittenen, metastasierten Weichteilsarkomen.
English title:
A Phase II Study to Investigate the Efficacy and Tolerability of Vorinostat in Patients Suffering from Advanced, Metastatic Soft Tissue Sarcoma.
Summary
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EudraCT number |
2008-008513-19 |
Trial protocol |
DE |
Global end of trial date |
20 Nov 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Jun 2022
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First version publication date |
24 Jun 2022
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Other versions |
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 |
SAHA-I
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00918489 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Universitätsklinikum Heidelberg
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Sponsor organisation address |
Im Neuenheimer Feld 672, Heidelberg, Germany, 69120
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Public contact |
Prof. Dr. G. Egerer, Universitätsklinikum Heidelberg
Medizinische Klinik und Poliklinik V, +496221 56 8002, Gerlinde.Egerer@med.uni-heidelberg.de
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Scientific contact |
Prof. Dr. G. Egerer, Universitätsklinikum Heidelberg
Medizinische Klinik und Poliklinik V, +496221 56 8002, Gerlinde.Egerer@med.uni-heidelberg.de
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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 |
05 Aug 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Nov 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2013
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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 |
Investigation of progression-free survival on the basis of RECIST criteria 1 year after treatment start
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Protection of trial subjects |
Adverse events were monitored.
A Data and Safety Monitoring Committee was establshed.
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Background therapy |
- | ||
Evidence for comparator |
not applicable | ||
Actual start date of recruitment |
02 Jun 2010
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Long term follow-up planned |
No
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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 |
Germany: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
30
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From 65 to 84 years |
9
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85 years and over |
1
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Recruitment
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Recruitment details |
Patients with metastatic soft tissue sarcoma failing 1 °-line anthracycline-based chemotherapy | ||||||||||
Pre-assignment
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Screening details |
Criteria for inclusion: • Histologically proven advanced or metastatic soft tissue sarcoma • Age: 18 years • Previous anthracycline-based, 1°-line chemotherapy • Life expectancy >/= 12 weeks • Adequate bone marrow, liver- and renal function • Negative pregnancy test | ||||||||||
Period 1
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Period 1 title |
Therapy (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 |
not applicable
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Arms
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Arm title
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Therapy | ||||||||||
Arm description |
- | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Vorinostat
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
400 mg per o, followed by a therapy-free period 7 dayss for 28 days
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Baseline characteristics reporting groups
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Reporting group title |
Therapy
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Therapy
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Reporting group description |
- |
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End point title |
Progression-free survival [1] | ||||||||
End point description |
Disease status was assessed by CT and/or MRI scans applying RECIST criteria every three months. Progression-free survival was defined as time from treatment start to disease progression or patient's death.
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End point type |
Primary
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End point timeframe |
1 year after start of study
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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: Single arm study, no comparative statistics applicable (feasibility study) |
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Notes [2] - The numer displayed as arithmetic mean is actually the proportion (48% progression free survival) |
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No statistical analyses for this end point |
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End point title |
Overall survival | ||||||||
End point description |
Overall survival was defined as time from treatment start patient's death or last follow-up.
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End point type |
Secondary
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End point timeframe |
1 year
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Notes [3] - number displayed as result is proportion of patients with overall survival as defined in description |
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No statistical analyses for this end point |
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End point title |
Pharmacokinetic analyses | ||||||
End point description |
Data on pharmacokinetics were available for 8 subjects (male=4. female=4. median age=62 years) . In plasma samples, mean Gmax (maximum concentration) , tmax (time to reach max. concentration), AUG (area under the plasma concentration time curve), t112 (elimination half-life) and GI/F (apparent total clearance) were 350 ng/ml , 101 min, 71.1 min*µg/ml , 103 min and 5903 ml/ min. The corresponding parameters in PBMGs were 558 ng/ml , 97.5 min, 208.4 min*µg/ml , 286 min and 2475 ml /min, respectively. The AUG plasma/PBMG ratio was 2.93, indicating accumulation of vorinostat in PBMGs. Differences in AUG (p=.008) and t112 (p= . 01) reached statistical significance.
It was not possible to enter these data as measurable due to technical reasons (no dispersion values available).
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End point type |
Secondary
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End point timeframe |
Subset of 8 patients, examined within study period
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Notes [4] - The count displayed here is the number of patients included in pharmacokinetics substudy. |
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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 |
During treatment and follow-up
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Therapy
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Reporting group description |
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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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01 Mar 2010 |
Study Protocol: More detailed description of the statistical evaluation of study data
ICF: More detailed description of possible risks related to the study medication, deletion of the currative
approach of the trial, information of sufficient anticontraception in male volunteers, report obligation of
investigator in case of positive serology for hepatitis and HIV. |
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20 Apr 2010 |
Samples for pharmacokinetic examination |
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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/27367154 |