Clinical Trial Results:
Phase Ib/II Multicentric Study Combining Glasdegib with temozolomide in patients with newly diagnosed Glioblastoma, safety and preliminary efficacy for the combination.
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Summary
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EudraCT number |
2017-002410-31 |
Trial protocol |
ES |
Global end of trial date |
29 Nov 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Feb 2026
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First version publication date |
27 Feb 2026
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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 |
GEINO-1602
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03466450 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Grupo Español de Investigación en Neurooncología
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Sponsor organisation address |
Velazquez St, 7-3o, Madrid, Spain, 28001
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Public contact |
Federico Nepote, MFAR Clinical Research, +34 934344412, investigacion@mfar.net
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Scientific contact |
Federico Nepote, MFAR Clinical Research, +34 934344412, investigacion@mfar.net
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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 Apr 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Nov 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Nov 2023
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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 |
Phase Ib: To determine the MTD and RDP2 are the primary endpoint of this part of the study. The MTD is defined as the dose at which one-third of patients experienced dose-limiting toxicity (DLT) from Glasdegib and/or TMZ using a standard “3+3” dose escalation determined from the toxicities during the first 12 weeks of therapy. The RDP2 is defined as the dose at which equal or fewer than one-sixth of patients experienced dose-limiting toxicity (DLT) form Glasdegib and/or TMZ using a standard “3+3” dose escalation determined from the toxicities during the first 12 weeks of therapy.
Phase II: To evaluate overall survival.
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Protection of trial subjects |
All patient signed the informed consent. The project comply with the local regulations on data protection (GDPR).
The trial was approved by the competent authority in Spain (Agencia Española de Medicamentos y Productos Sanitarios; AEMPS) and the ethics committee from Hospital Ramon y Cajal. The trial was conducted in accordance with the ethics principles of the Declaration of Helsinki and with the Good Clinical Practice (GCP) guidelines defined by the International Council for Harmonisation (ICH).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 2017
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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 |
Spain: 79
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Worldwide total number of subjects |
79
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EEA total number of subjects |
79
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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) |
79
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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 |
- | ||||||||
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Pre-assignment
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Screening details |
- | ||||||||
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Pre-assignment period milestones
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Number of subjects started |
79 | ||||||||
Number of subjects completed |
74 | ||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
did not received glasdegib: 1 | ||||||||
Reason: Number of subjects |
dose scalation phase at 100 mg/d: 4 | ||||||||
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Period 1
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Period 1 title |
Phase II (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. This is a single arm trial.
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Arms
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Arm title
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Experimental arm | ||||||||
Arm description |
Patients receive Temozolamide (TMZ) at 75 mg/m2 /d concurrently with radiotherapy (RT) for a maximum of 42 days. At 4 weeks after RT completion, patients will start taking TMZ at 150 mg/m2/d for the first 5 days of a 28-day cycle. If first cycle is well tolerated, patients will receive TMZ at 200 mg/m2/d for the first 5 days of every subsequent 28-day cycle for another 5 cycles. Glasdegib will be continued until progression, unacceptable toxicity, non-compliance, consent withdrawal and/or 2 years of glasdegib administration. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Glasdegib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose Levels of Glasdegib in Phase Ib:
100 mg / day
75 mg / day
Dose Level of Glasdegib in Phase II:
75 mg / day
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Some patients were included in the Phase Ib (dose escalation phase) |
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Baseline characteristics reporting groups
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Reporting group title |
Phase II
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental arm
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Reporting group description |
Patients receive Temozolamide (TMZ) at 75 mg/m2 /d concurrently with radiotherapy (RT) for a maximum of 42 days. At 4 weeks after RT completion, patients will start taking TMZ at 150 mg/m2/d for the first 5 days of a 28-day cycle. If first cycle is well tolerated, patients will receive TMZ at 200 mg/m2/d for the first 5 days of every subsequent 28-day cycle for another 5 cycles. Glasdegib will be continued until progression, unacceptable toxicity, non-compliance, consent withdrawal and/or 2 years of glasdegib administration. | ||
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End point title |
Glasdegib Dose [1] | ||||
End point description |
For Phase Ib, The recommended dose for phase 2 (RDP2) of Glasdegib administered with temozolomide during and
after RT.
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End point type |
Primary
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End point timeframe |
12 weeks
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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: This is a single arm trial. No statistical comparisons are feasible |
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| No statistical analyses for this end point | |||||
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End point title |
Overall Survival [2] | ||||||||
End point description |
For Phase II, time between the start of treatment to death. Here we report the percentage of patients alive at 15 months after the start of treatment, estimated by Kaplan Meier method
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End point type |
Primary
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End point timeframe |
15 months
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| Notes [2] - 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: This is a single arm trial. No statistical comparisons are feasible |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) | ||||||||
End point description |
Time between the start of treatment and progression of disease or death, whichever comes first. Here we report the median time to progression or death
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Adverse events (safety) | ||||||||||
End point description |
Based on the number and type of adverse events (AEs) reported since the start of treatment and throughout the study period. Here we report the number of patients who experienced adverse events.
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||||
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End point title |
AEs grade 3-5 (safety) | ||||||||||
End point description |
Based on the number and type of adverse events (AEs) reported since the start of treatment and throughout the study period. Here we report the number of patients who experienced adverse events.
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||||
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End point title |
AEs any grade related to study treatment (Safety) | ||||||||||
End point description |
Based on the number and type of adverse events (AEs) reported since the start of treatment and throughout the study period. Here we report the number of patients who experienced adverse events.
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||||
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End point title |
AEs grade 3-5 related to study treatment (Safety) | ||||||||||
End point description |
Based on the number and type of adverse events (AEs) reported since the start of treatment and throughout the study period. Here we report the number of patients who experienced adverse events.
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||||
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End point title |
Objective response rate (ORR) | ||||||||||||||||
End point description |
Based tumor imaging scans locally assessed by the investigators following the response assessments in neurooncology (RANO) criteria. Here we report the best response achieved for each patient.
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End point type |
Secondary
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End point timeframe |
24 months
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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 |
24 months
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
Experimental arm
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Reporting group description |
Patients receive Temozolamide (TMZ) at 75 mg/m2 /d concurrently with radiotherapy (RT) for a maximum of 42 days. At 4 weeks after RT completion, patients will start taking TMZ at 150 mg/m2/d for the first 5 days of a 28-day cycle. If first cycle is well tolerated, patients will receive TMZ at 200 mg/m2/d for the first 5 days of every subsequent 28-day cycle for another 5 cycles. Glasdegib will be continued until progression, unacceptable toxicity, non-compliance, consent withdrawal and/or 2 years of glasdegib administration. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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19 Nov 2018 |
- The indications received by the AEMPS on August 10, 2018 related to the query sent on August 7, 2018, by MFAR on behalf of the Sponsor, to determine the possible failure to include a patient in phase I.
Along with this amendment, we sent the document "Study status report as of October 2018" as requested by the AEMPS on August 10, 2018.
- This relevant amendment is used to introduce some changes to the Protocol and Patient Information Sheet and Informed Consent and to correct some errors in the documents. |
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12 Jul 2019 |
Change of Principal investigator in Hospital Universitario y Politécnico la Fe |
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05 Aug 2020 |
1. Substantial modification of Parts I and II due to the update of the Glasdegib Investigator's Manual and the safety information provided in the patient information sheet/informed consent.
2. Change of principal investigator at the Hospital Universitari i Politècnic La Fe in the new version of the protocol, this change was already reported to the local Authorities in the corresponding amendment No. 2, approved by the CEIm on July 12, 2019.
3. Modifications in the presentation of the medication, Glasdegib tablets go from being only Round White Film Coated Tablet 25 mg or Round Film Coated Tablets 100 mg to possibly also being Round Pale Orange Film Coated Tablet 25 mg. A new ATC code must be added in section D3.3, which will be L01XX63.
4. Incorporation of the AEMPS resolution into the evaluation of relevant amendment no. 3: “The definition of Dose Limiting Toxicity (DLT) should not vary throughout the study. |
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23 Dec 2021 |
● Substantial modification of Parts I and II due to the update of the Glasdegib Investigator's Manual and the safety information provided in the patient information sheet/informed consent.
● Addition of an extra point in the protocol for the extraction of pharmacokinetic samples in patients in cycle 6 day 1 of the adjuvant phase of treatment. The informed consent has also been modified to reflect this point.
● Typographical errors detected in the previous version have been corrected.
● The description of the color indicated on the Glasdegib 25mg label has been homogenized according to the specifications of the SmPC; the color specified in the SmPC is yellow, instead of sepia. |
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27 Apr 2023 |
Substantial modification of Parts I and II due to update of the Glasdegib Investigator's Manual and safety information provided in the patient information sheet/informed consent. |
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28 Jun 2023 |
Change of principal invertigator in ICO Badalona |
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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. | |||
| Not applicable | |||
