Clinical Trial Results:
Multicenter, randomized, non-comparative, open-label phase II trial on the efficacy of Ortataxel and Fotemustine in recurrent glioblastoma
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Summary
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EudraCT number |
2012-003618-15 |
Trial protocol |
IT |
Global end of trial date |
11 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jan 2020
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First version publication date |
03 Jan 2020
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Other versions |
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Summary report(s) |
study journal article |
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 |
IRFMN-GBM-6272
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01989884 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
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Sponsor organisation address |
Via Giuseppe La Masa, 19, Milano, Italy, 20156
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Public contact |
Laboratory of Methodology for Clinical Research, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, +39 0239014650, elena.biagioli@marionegri.it
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Scientific contact |
Laboratory of Methodology for Clinical Research, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, +39 0239014650, elena.biagioli@marionegri.it
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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 |
09 Feb 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Nov 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Nov 2016
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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 |
The study was primarily aimed at assessing the efficacy of Ortataxel in terms of progression free survival at 6 months (PFS-6) in patients with recurrent glioblastoma.
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Protection of trial subjects |
Before any administration of study drug, the following examinations were required: relevant physical examinations (symptom-directed physical examination, neurological examination, weight), a check of patients vital signs, relevant laboratory assessments.
When a patient discontinued the study treatment, regardless of the reason for discontinuation, the patient had to return to the clinic within 30 days (± 7 days) after the last infusion of study for a visit to monitor any possible adverse reactions.
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Background therapy |
No background therapy was planned due to the absence of effective therapies for patients with this stage of glioblastoma | ||
Evidence for comparator |
Not comparative trial | ||
Actual start date of recruitment |
26 Nov 2013
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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 |
Italy: 38
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Worldwide total number of subjects |
38
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EEA total number of subjects |
38
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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) |
38
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study enrolment started on 26th Nov 2013 and was closed on 23rd Dec 2015. Patients were enrolled from 6 experimental sites. A total of 40 patients were enrolled and assigned to Ortataxel. On October 2014 the calibration was eliminated thanks to an amendment to the protocol. Until October 2014, five patients had been assigned to Fotemustine. | ||||||
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Pre-assignment
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Screening details |
Patients with histologically confirmed GBM in recurrence/PD after surgery (or biopsy), standard radiotherapy and chemotherapy with Temozolomide (no more than one prior line of Temozolomide).Patients who had undergone recent surgery for recurrent or PD were eligible provided that 14 days had elapsed and 7 day for core or needle biopsy. | ||||||
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Pre-assignment period milestones
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Number of subjects started |
38 | ||||||
Number of subjects completed |
38 | ||||||
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Period 1
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Period 1 title |
Trial closed (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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Ortataxel arm | ||||||
Arm description |
Ortataxel 75 mg/m² intravenous every 21 days. Study treatment continued until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ortataxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ortataxel 75 mg/m² administered intravenous every 21 days until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death.
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Baseline characteristics reporting groups
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Reporting group title |
Ortataxel arm
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Reporting group description |
Ortataxel 75 mg/m² intravenous every 21 days. Study treatment continued until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
per protocol analysis set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per protocol (PP) population included all patients who were registered, with no major violations of the eligibility criteria or during study conduction, who received at least 2 cycles of treatment (unless they interrupted treatment for progressive disease or death) and whose disease is assessed
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Subject analysis set title |
Intention to treat analysis set
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The intention to treat (ITT) population included all patients who were registered, with no major violations of the eligibility criteria or during study conduction.
2 patients were excluded from the ITT ppopulation due to major violations.
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End points reporting groups
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Reporting group title |
Ortataxel arm
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Reporting group description |
Ortataxel 75 mg/m² intravenous every 21 days. Study treatment continued until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. | ||
Subject analysis set title |
per protocol analysis set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per protocol (PP) population included all patients who were registered, with no major violations of the eligibility criteria or during study conduction, who received at least 2 cycles of treatment (unless they interrupted treatment for progressive disease or death) and whose disease is assessed
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Subject analysis set title |
Intention to treat analysis set
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The intention to treat (ITT) population included all patients who were registered, with no major violations of the eligibility criteria or during study conduction.
2 patients were excluded from the ITT ppopulation due to major violations.
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End point title |
progression free survival at 6 months | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
from patient registration into the trial until progression or death at 6 months, whichever occurs first
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Attachments |
Untitled (Filename: ortataxelarticle.pdf) |
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Statistical analysis title |
Primary efficacy endpoint analysis | |||||||||
Statistical analysis description |
The PFS-6 with both 80% and 95% confidence intervals (CI) will be estimated by means of Kaplan-Meier method.
The one-tailed statistical hypotheses are: p0 ≤0.20 (null hypothesis) versus pA 0.35 (alternative hypothesis), where p is the estimated probability of being alive and progression-free at 6 months from registration.
According to the sample size assumptions, the following conclusions based on 58 eligible patients will be possibly drawn:
if there will be 15 or less patients alive an
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Comparison groups |
Ortataxel arm v per protocol analysis set
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Number of subjects included in analysis |
73
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
≤ 0.02 | |||||||||
Method |
Logrank | |||||||||
Confidence interval |
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End point title |
Dose-intensity | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
during treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall survival 9 months | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from enrollment untill death or 9 months, whichever occurs first
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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 |
from enrollment until 30 days after the end of treatment
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI-CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
all patients who received the treatment
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Reporting group description |
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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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01 Oct 2014 |
the calibration arm with Fotemustine was closed. |
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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/3072653 |
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