Clinical Trial Results:
The histone deacetylase inhibitor (HDAC) valproic acid as second line treatment for hormone refractory metastatic prostate cancer. A phase II. study.
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Summary
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EudraCT number |
2006-003554-15 |
Trial protocol |
SK |
Global end of trial date |
28 Feb 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Aug 2022
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First version publication date |
14 Aug 2022
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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 |
18031977
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Národný onkologický ústav
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Sponsor organisation address |
Klenova 1, Bratislava, Slovakia, 833 10
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Public contact |
Prof Michal Mego MD, DSc, Národný onkologický ústav, 00421 259378108, michal.mego@nou.sk
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Scientific contact |
Prof Michal Mego MD, DSc, Národný onkologický ústav, 00421 259378108, michal.mego@nou.sk
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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 |
28 Nov 2008
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Nov 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Feb 2009
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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 |
To determine the efficacy (as measured by tumor response) of valproic acid given orally to patients with hormone refractory metastatic prostate cancer after first line chemotherapy.
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Protection of trial subjects |
All the procedures performed in study involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual paricipants included in the study.
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
15 Nov 2006
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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 |
Slovakia: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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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) |
7
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Between December 2006 and November 2007 nine patients with hormone refractory metastatic prostate cancer who have progressed on standard first line chemotherapy.were enrolled. | ||||||
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Pre-assignment
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Screening details |
9 patients with metstatic HRPC were screened, all subjects met Inclusion/ Exclusion criteria. Median age was 64 years ( 54-79 years), Karnofski PS 90% ( range: 80-100 %). All patients were pretreated with doxataxel based chemtherapy. Additionally 8 patients were also pretreated with vinorelbin and 3 patients with mitoxantron-based therapy. | ||||||
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Period 1
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Period 1 title |
Overall Study ( 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 | ||||||
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Arms
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Arm title
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valproic acid | ||||||
Arm description |
Valproic acid will be administered at a dose of 20mg/kg/day orally once a day. One cycle of therapy consists of 28 days.A minimum of 2 cycles of the treatment will be administered to each patient in the absence of unacceptable toxicity or disease progression. Treatment cycles will be repeated until progression or unacceptable toxicity. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Valproic acid
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Investigational medicinal product code |
21/034/83-S/C
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Other name |
Everiden , Orfiril, Desitin, Convulex
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Valproic acid will be administered at a dose of 20mg/kg/day orally once a day. One cycle of therapy consists of 28 days. In the first cycle the starting dose is 10mg/kg/day (dose level –2), which is escalated on day 4 (15mgkg/day; dose level –1) and on day 7 (dose 20mg/kg/day; dose level 0) in the absence of grade 3-4 neurological toxixicity. In other cycles the starting dose is 20mg/kg/day, or the dose according to dose adjustments from the previous treatment cycle.
Doses will be reduced for hematological and other adverse events. A minimum of 2 cycles of the treamtment will be administered to each patient in the absence of unacceptable toxicity or disease progression. Treatment cycles will be repeated untill progression or unacceptable toxicity.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study ( overall period)
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Reporting group description |
Non-randomized, open-label, single centre trial with treatment regimen consisted of valproic acid given orally at a dose of 20mg/kg/day orally once a day. A minimum of 2 cycles of the treamtment will be administered to each patient and repeated until progression or unacceptable toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Overall study (overall period)
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Non-randomized, open-label, single centre trial with treatment regimen consisted of valproic acid given orally at a dose of 20mg/kg/day orally once a day. A minimum of 2 cycles of the treamtment will be administered to each patient and repeated until progression or unacceptable toxicity.
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End points reporting groups
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Reporting group title |
valproic acid
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Reporting group description |
Valproic acid will be administered at a dose of 20mg/kg/day orally once a day. One cycle of therapy consists of 28 days.A minimum of 2 cycles of the treatment will be administered to each patient in the absence of unacceptable toxicity or disease progression. Treatment cycles will be repeated until progression or unacceptable toxicity. | ||
Subject analysis set title |
Overall study (overall period)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Non-randomized, open-label, single centre trial with treatment regimen consisted of valproic acid given orally at a dose of 20mg/kg/day orally once a day. A minimum of 2 cycles of the treamtment will be administered to each patient and repeated until progression or unacceptable toxicity.
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End point title |
Response rate (PSA response) | |||||||||
End point description |
PSA decline of at least 50%, which must be confirmed by a second PSA value 4 or more weeks later.The reference PSA for these declines should be a PSA measured within 2 weeks before starting therapy. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period.
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End point type |
Primary
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End point timeframe |
PSA will be measured at baseline and every 4 weeks following first dose.
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Statistical analysis title |
descriptive statistics | |||||||||
Comparison groups |
valproic acid v Overall study (overall period)
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Number of subjects included in analysis |
18
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 5 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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End point title |
Time to progression | ||||||||||||
End point description |
In the absence of evidence of clinical progression, the time to PSA progression is an appropriate outcome to report (especially for noncytotoxic agents). PSA progression may occur before clinical progression. The start of the time to PSA progression is the day treatment is initiated. If at least a 50% decline in PSA has been achieved, the end date is the time the PSA has increased 25% above the nadir at a minimum of 5 ng/mL (this is the same as the parameter for PSA response). For patients without a PSA decrease of this magnitude (or no decrease in PSA), the end point for progression will be calculated at the time a 25% increase in PSA has been achieved. All end dates require a confirmatory PSA.
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End point type |
Secondary
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End point timeframe |
Time to progression was calculated from the start of the treatment until progression or death.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Toxicity | |||||||||
End point description |
Toxicity grade 3-4
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End point type |
Secondary
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End point timeframe |
From start of the treatment to last follow up.
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| Notes [1] - 2 subjects experienced toxicity grade 3-4 |
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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 |
Adverse events were recorded from start of study treatment until last follow up.
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Adverse event reporting additional description |
Grade 3 and 4 non serious or any grade serious adverse events are reported.
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Assessment type |
Systematic | ||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||
Dictionary version |
3.0
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Reporting groups
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Reporting group title |
all subjects
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Reporting group description |
Grade 3 and 4 non serious or any grade serious adverse events are reported. | ||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||
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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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03 Nov 2006 |
Everiden is replaced with Convulex or Orfiril,. Composition is deleted. |
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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 | |||
